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1.  Host Genetics and HIV-1 Viral Load Set-point in African-Americans 
AIDS (London, England)  2009;23(6):673-677.
In a recent genome-wide association study of HIV-1-infected individuals in the Euro-CHAVI cohort, viral load set-point was strongly associated with genotypes defined by two SNPs (rs9264942 and rs2395029) within the human MHC region on chromosome 6. We attempted to confirm this finding in African-Americans and assess if these SNPs are in linkage disequilibrium (LD) with HLA class I alleles that mediate innate and adaptive immunity.
Our analyses relied on 121 African American adolescents with chronic HIV-1 infection and quarterly immunological and virological outcome measures in the absence of therapy.
PCR-based techniques were used to genotype two SNPs along with HLA class I alleles. Their associations with HIV-1 viral load set-point and longitudinal CD4+ and CD8+CD38+ T-cell counts were tested in univariate and multivariate models.
The CC genotype at rs9264942 was associated with reduced viral load but not with immunological outcomes or category of disease control. Consistent associations of HLA-B*57 (mostly B*5703) with favorable virological and immunological outcomes were observed, but not rs2395029G allele at the HCP5 locus, which is in absolute linkage disequilibrium with B*5701 (in individuals of European descent), and not B*5703.
While rs9264942 and B*57 (but not rs2395029G) are clearly associated with control of viral load set-point among African-Americans, fine-mapping of MHC SNPs in populations of African and European descent should help reveal the true variants and the underlying functional mechanisms.
PMCID: PMC2663898  PMID: 19276793
HIV-1; genetics; viral load; African American
2.  Regulatory Polymorphisms in the Cyclophilin A Gene, PPIA, Accelerate Progression to AIDS 
PLoS Pathogens  2007;3(6):e88.
Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4+ T-cell loss (relative hazard = 3.7, p = 0.003) in African Americans. Among European Americans, these alleles were also associated with a significant trend to more rapid progression to AIDS in a multi-point categorical analysis (p = 0.005). Both SNPs showed differential nuclear protein-binding efficiencies in a gel shift assay. In addition, one SNP (SNP5) located in the 5′ UTR previously shown to be associated with higher ex vivo HIV-1 replication was found to be more frequent in HIV-1-positive individuals than in those highly exposed uninfected individuals. These results implicate regulatory PPIA polymorphisms as a component of genetic susceptibility to HIV-1 infection or disease progression, affirming the important role of PPIA in HIV-1 pathogenesis.
Author Summary
Individual risk of acquiring HIV type 1 (HIV-1) infection and developing AIDS is not equal; some people are more prone to HIV/AIDS than others. Susceptibility to HIV-1/AIDS is likely determined by a combination of environmental, viral, and host genetic factors. Genetic variations in host cellular factors involved in HIV-1 cell entry, replication, and host defense have been found to affect susceptibility to HIV-1/AIDS. In this report, we focused on the gene PPIA that encodes cyclophilin A, a human cellular protein that is incorporated into the HIV-1 virion and promotes viral replication. We studied genetic variation in the PPIA gene in persons with different susceptibility levels to HIV-1 infection or different rates of disease progression. We found that individuals who processed two functional variants in the promoter region of PPIA had higher risk of CD4+ T-cell loss or progression to AIDS-defining diseases. We also observed that an additional variant occurred more frequently in HIV-1-infected individuals compared to HIV-1-exposed, but uninfected, individuals. These results suggest that genetic variation in PPIA may influence host susceptibility to HIV-1 infection or disease progression and targeting PPIA might provide therapeutic benefit.
PMCID: PMC1894826  PMID: 17590083
3.  Mitochondrial DNA variation and virologic and immunological HIV outcomes in African Americans 
AIDS (London, England)  2014;28(13):1871-1878.
To evaluate the impact of mitochondrial DNA (mtDNA) haplogroups on virologic and immunological outcomes of HIV infection.
HAART-naive African American adolescent participants to the Reaching for Excellence in Adolescent Care and Health study.
The mtDNA haplogroups were inferred from sequenced mtDNA hypervariable regions HV1 and HV2 and their predictive value on HIV outcomes were evaluated in linear mixed models, controlled for human leukocyte antigen (HLA)-B27, HLA-B57 and HLA-B35-Px alleles and other covariates.
We report data showing that the mtDNA L2 lineage, a group composed of L2a, L2b and L2e mtDNA haplogroups in the studied population, is significantly associated (beta=−0.08; Bonferroni-adjusted P=0.004) with decline of CD4+ T cells (median loss of 8 ± 1 cells per month) in HAART-naive HIV-infected individuals of African American descent (n=133). No significant association (P<0.05) with set-point viral load was observed with any of the tested mtDNA haplogroups. The present data concur with previous findings in the AIDS Clinical Trials Group study 384, implicating the L2 lineage with slower CD4+ T-cell recovery after antiretroviral therapy in African Americans.
Whereas the L2 lineage showed an association with unfavorable immunological outcomes of HIV infection, its phylogenetic divergence from J and U5a, two lineages associated with accelerated HIV progression in European Americans, raises the possibility that interactions with common nucleus-encoded variants drive HIV progression. Disentangling the effects of mitochondrial and nuclear gene variants on the outcomes of HIV infection is an important step to be taken toward a better understanding of HIV/AIDS pathogenesis and pharmacogenomics.
PMCID: PMC5004594  PMID: 24932613
AIDS; CD4+ cell count; HIV; HLA; mitochondrial haplogroup; viral load
4.  Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach 
PLoS Medicine  2007;4(8):e257.
Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
In an observational cohort study from Côte d'Ivoire, François Dabis and colleagues report on prevention of mother-to-child HIV transmission among women receiving antiretroviral therapy according to World Health Organization recommendations.
Editors' Summary
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte (“T cell”) count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at
World Health Organization has a page on prevention of mother-to-child transmission of HIV
“Women, Children, and HIV” is a resource site from the François Xavier Bagnoud Center and UCSF
The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
PMCID: PMC1949842  PMID: 17713983
5.  Variants in Host Viral Replication Cycle Genes Are Associated With Heterosexual HIV-1 Acquisition in Africans 
Supplemental Digital Content is Available in the Text.
We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.
Using a nested case–control study within a cohort of heterosexual HIV-1–serodiscordant couples, we genotyped 475 haplotype-tagging single-nucleotide polymorphisms (tagSNPs) and 18 SNPs previously associated with HIV-1 transmission and/or progression (candidate SNPs) in 51 host genes. We used logistic and Cox proportional hazard regression with adjustment for sex, age, and population stratification to detect SNP associations with HIV-1 acquisition, plasma HIV-1 set point, and a composite measure of HIV-1 disease progression. Significant thresholds for tagSNP, but not candidate SNP, associations were subjected to Bonferroni correction for multiple testing.
We evaluated 491 HIV-1–infected and 335 HIV-1–uninfected individuals for 493 SNPs, 459 of which passed quality control filters. Candidate SNP PPIA rs8177826 and tagSNP SMARCB1 rs6003904 were significantly associated with HIV-1 acquisition risk (odds ratio = 0.14, P = 0.03, and odds ratio = 2.11, Pcorr = 0.01, respectively). Furthermore, the TT genotype for CCR5 rs1799988 was associated with a mean 0.2 log10 copies per milliliter lower plasma HIV-1 RNA set point (P = 0.04). We also identified significant associations with HIV-1 disease progression for variants in FUT2 and MBL2.
Using a targeted gene approach, we identified variants in host genes whose protein products interact with HIV-1 during the virus replication cycle and were associated with HIV-1 outcomes in this African cohort.
PMCID: PMC4025588  PMID: 24463784
HIV; cell cycle genes; genotype–phenotype association; HIV genetics; Africa
6.  Variants in Interleukin Family of Cytokines Genes Influence Clearance of High Risk HPV in HIV-1 Coinfected African-American Adolescents 
Human immunology  2013;74(12):10.1016/j.humimm.2013.08.010.
Our work aimed to examine the potential influence of variants in interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance. Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive African-American female adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single nucleotide polymorphisms (SNPs) within the exons, 5′ untranslated region (UTR) and 3′ UTR sequences of 27 immune-related candidate genes encoding interleukin family of cytokines. Cox proportional hazard models were used to determine the association of type- specific HPV clearance adjusting for time-varying CD4+ T-cell count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were significantly (p< 0.001) associated with five SNPs (rs228942, rs419598, rs315950, rs7737000, rs9292618) mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed genetic variants in interleukin family of cytokines modulate HR-HPV clearance in HIV-1 seropositive African-Americans that warrants replication.
PMCID: PMC3842375  PMID: 23973891
HPV clearance; genetic association; interleukins; HIV-1 seropositive; African American adolescents
7.  Proceedings of The 8th Romanian National HIV/AIDS Congress and The 3rd Central European HIV Forum 
Alexiev, Ivailo | Dimitrova, Reneta | Gancheva, Anna | Kostadinova, Asya | Stoycheva, Mariyana | Nikolova, Daniela | Elenkov, Ivaylo | Tilișcan, Cătălin | Predescu, Mioara | Păunescu, Bogdan | Streinu-Cercel, Anca | Săndulescu, Oana | Șchiopu, Claudiu Mihai | Hristache, Mădălina | Brîndușe, Lăcrămioara Aurelia | Streinu-Cercel, Adrian | Todorovic, Marija | Siljic, Marina | Salemovic, Dubravka | Nikolic, Valentina | Pesic-Pavlovic, Ivana | Ranin, Jovan | Jevtovic, Djordje | Stanojevic, Maja | Tudor, Ana Maria | Vlad, Delia | Mărdărescu, Mariana | Petrea, Sorin | Petre, Cristina | Neagu-Drăghicenoiu, Ruxandra | Ungurianu, Rodica | Cibea, Alina | Chirilă, Odette | Anghelina, Cristian | Coserea, Ileana | Krikelli, Pantelia-Amalia | Pavlitina, Eirini | Psichogiou, Mina | Lamnisos, Demetris | Williams, Leslie | Korobchuk, Anya | Skaathun, Britt | Smyrnov, Pavlo | Schneider, John | Sypsa, Vana | Paraskevis, Dimitrios | Hatzakis, Angelos | Friedman, Samuel R. | Nikolopoulos, Georgios K. | Dragović, Gordana | Srdić, Danica | Khawla, Al Musalhi | Soldatović, Ivan | Nikolić, Jelena | Jevtović, Djordje | Nair, Devaki | Temereanca, Aura | Rosca, Adelina | Ene, Luminita | Soontornniyomkij, Benchawa | Diaconu, Carmen | Dita, Claudia | Achim, Cristian | Ruta, Simona | Benea, Șerban | Moroti, Ruxandra | Jipa, Raluca | Manea, Eliza | Stan, Andrada | Benea, Elisabeta | Oțelea, Dan | Hristea, Adriana | Hristea, Adriana | Lăpădat, Irina | Jipa, Raluca | Moroti, Ruxandra | Benea, Șerban | Antonică, Doina | Panait, Irina | Petre, Roxana | Kowalska, Justyna D. | Pietraszkiewicz, Ewa | Grycner, Ewa | Firlag-Burkacka, Ewa | Horban, Andrzej | Vlaicu, Ovidiu | Bănică, Leontina | Paraschiv, Simona | Tudor, Ana-Maria | Moroti, Ruxandra | Oțelea, Dan | Dimitrijević, Bojana | Soldatović, Ivan | Jevtović, Đorđe | Kusić, Jovana | Salemović, Dubravka | Ranin, Jovan | Dragović, Gordana | Florea, Dragoș | Bădicuț, Ioana | Rafila, Alexandru | Camburu, Cornel | Histrea, Adriana | Frățilă, Mihaela | Oțelea, Dan | Gmizic, Ivana | Salemovic, Dubravka | Pesic-Pavlovic, Ivana | Siljic, Marina | Nikolic, Valentina | Djonin-Nenezic, Miljana | Milosevic, Ivana | Brmbolic, Branko | Stanojevic, Maja | Streinu-Cercel, Anca | Săndulescu, Oana | Neguț, Alina Cristina | Predescu, Mioara | Mărdărescu, Alexandra | Săndulescu, Mihai | Streinu-Cercel, Adrian | Pérez, Ana Belen | Chueca, Natalia | Álvarez, Marta | Alados, Juan Carlos | Rivero, Antonio | Vera, Francisco | Delgado, Marcial | Salmeron, Javier | Jiménez, Miguel | Blanco, Maria José | Diago, Moises | Garcia-deltoro, Miguel | Alvarez, Marta | Téllez, Francisco | García, Federico | Tănase, Diana | Manea, Eliza | Bacruban, Rodica | Florea, Dragoș | Oțelea, Dan | Rafila, Alexandru | Mărdărescu, Mariana | Hristea, Adriana | Grgic, Ivana | Planinic, Ana | Santak, Maja | Gorenec, Lana | Lepej, Snjezana Zidovec | Vince, Adriana | Manea, Eliza | Hristea, Adriana | Benea, Șerban | Moroti, Ruxandra | Tănase, Diana | Niculae, Cristian M. | Merisor, Simona | Jipa, Raluca | Paraskevis, Dimitrios | Kostaki, Evangelia | Nikolopoulos, Georgios K. | Sypsa, Vana | Psichogiou, Mina | Paraskeva, Dimitra | Skoutelis, Athanassios | Malliori, Meni | Friedman, Samuel R. | Hatzakis, Angelos | Hackiewicz, Malgorzata | Zabek, Piotr | Firlag-Burkacka, Ewa | Horban, Andrzej | Kowalska, Justyna Dominika | Lunar, Maja M. | Mlakar, Jana | Poljak, Mario | Bănică, Leontina | Martin, Eliza | Gheorghiță, Valeriu | Petrescu, Andrei | Oțelea, Dan | Popescu, Costin-Ioan | Paraschiv, Simona | Neaga, Emil | Ovidiu, Vlaicu | Juncu, Andrei | Bănică, Leontina | Paraschiv, Simona | Oțelea, Dan | Popescu, Costin-Ioan | Luca, Adrian | Lazăr, Florin | Luca, Anca Elena | Ene, Luminița | Achim, Cristian | Gingăraş, Cosmina | Anton, Ștefan Adrian | Rădoi, Roxana | Tetradov, Simona | Țârdei, Grațiela | Nica, Maria | Capşa, Razvan Alexandru | Achim, Cristian L. | Oprea, Cristiana | Ene, Luminița | Szymańska, Bogna | Gawron, Natalia | Pluta, Agnieszka | Łojek, Emilia | Firląg-Burkacka, Ewa | Horban, Andrzej | Bornstein, Robert | Burcoș, Olivia | Erscoiu, Simona Manuela | Cojanu, Filofteia Bănicioiu | Toderan, Andreea | Nica, Maria | Popa, Ionuț Cristian | Ceaușu, Emanoil | Calistru, Petre Iacob | Arbune, Manuela | Alexandrache, Mirela | Arbune, Anca-Adriana | Voinescu, Doina-Carina | Diaconu, Ioan-Alexandru | Stratan, Laurențiu | Aramă, Victoria | Nichita, Luciana | Diaconu, Alexandra | Negru, Anca | Orfanu, Alina | Leuștean, Anca | Ion, Daniela Adriana | Ianache, Irina | Oprea, Cristiana | Leuștean, Anca | Popescu, Cristina | Orfanu, Alina | Negru, Anca | Catana, Remulus | Murariu, Cristina | Diaconu, Ioan-Alexandru | Rădulescu, Mihaela | Tilișcan, Cătălin | Aramă, Victoria | Marincu, Iosif | Poptelecan, Patricia | Bică, Valeria | Lazăr, Florin | Tirnea, Livius | Ianache, Irina | Rădoi, Roxana | Nica, Manuela | Țârdei, Grațiela | Ene, Luminița | Ceaușu, Emanoil | Calistru, Petre | Oprea, Cristiana | Osoianu, Iurie | Halacu, Ala | Stoian, Andreea Cristina | Dumitrescu, Florentina | Diaconescu, Iulian | Cupșa, Augustin | Giubelan, Lucian | Ionescu, Loredana | Niculescu, Irina | Chiriac, Carmen | Șincu, Nina | Kezdi, Iringo Zaharia | Georgescu, Anca | Țilea, Brândușa | Girbovan, Cristina | Incze, Andrea | Fodor, Andrea | Cibea, Alina | Mărdărescu, Mariana | Petre, Cristina | Drăghicenoiu, Ruxandra | Ungurianu, Rodica | Tudor, Ana Maria | Vlad, Delia | Matei, Carina | Dumea, Elena | Petcu, Lucian Cristian | Cambrea, Simona Claudia | Dumitrescu, Florentina | Cupsa, Augustin | Stoian, Andreea Cristina | Giubelan, Lucian | Niculescu, Irina | Diaconescu, Iulian | Hurezeanu, Dan | Dragonu, Livia | Cotulbea, Mioara | Erscoiu, Simona Manuela | Popa, Ionuț Cristian | Stroie, Denisa | Ionescu, Petronela | Duță, Nedeea | Dobrea, Camelia | Voican, Irina | Ceaușu, Emanoil | Calistru, Petre Iacob | Lazăr, Florin | Giubelan, Lucian | Cupșa, Augustin | Diaconescu, Iulian | Dumitrescu, Florentina | Hurezeanu, Dan | Dragonu, Livia | Niculescu, Irina | Stoian, Andreea Cristina | Obretin, Oana | Stănescu, Mariana | Jianu, Mihai | Gorenec, Lana | Lepej, Snjezana Zidovec | Grgic, Ivana | Planinic, Ana | Bes, Janja Iscic | Vince, Adriana | Begovac, Josip | Horga, Luminița Elena | Itu, Corina | Horga, Luminița Elena | David-Aldea, Laura Augusta | Ciorogar, Anca | Jianu, Cristian | Lupșe, Mihaela | Caramangiu, Iuliana | Roșca, Ovidiu | Cialma, Monica | Ardeleanu, Andreea | Marincu, Iosif | Jipa, Raluca | Manea, Eliza | Benea, Șerban | Lăpădat, Irina | Irimescu, Nicoleta | Panait, Irina | Niculae, Cristian | Hristea, Adriana | Kusic, Jovana | Jevtovic, Djordje | Salemovic, Dubravka | Ranin, Jovan | Dimitrijevic, Bozana | Dragovic, Gordana | Aldea-David, Laura-Augusta | Manciuc, Carmen | Nicolau, Cristina | Prisăcariu, Liviu | Largu, Alexandra | Mărdărescu, Mariana | Streinu-Cercel, Adrian | Petre, Cristina | Iancu, Marieta | Vintilă, Sanda | Vitelaru, Daniela | Ionel, Iosif | Șchiopu, Claudiu Mihai | Mărdărescu, Alexandra-Henriette | Micsanschi, Pavel | Holban, Tiberiu | Bîstrițchi, Ina | Pârțână, Lucia | Nagîț, Angela | Popovici, Svetlana | Talmaci, Maria | Cucerova, Irina | Mitrescu, Sorina Georgiana | Mihalcea, Dana | Caramangiu, Iulia | Roșca, Ovidiu | Maricu, Iosif | Negru, Anca | Munteanu, Daniela | Aramă, Victoria | Mihăilescu, Raluca | Diaconu, Ioan | Catana, Remulus | Popescu, Cristina | Orfanu, Alina | Leuștean, Anca | Rădulescu, Mihaela | Tilișcan, Cătălin | Năstase, Raluca | Molagic, Violeta | Duport, Irina | Dragomirescu, Cristina | Aramă, Ștefan Sorin | Negruț, Nicoleta M. | Niță, Violeta Elena | Munteanu, Daniela Ioana | Mihăilescu, Raluca | Diaconu, Ioan | Negru, Anca | Popescu, Cristina | Aramă, Victoria | Orfanu, Alina | Popescu, Cristina | Leuștean, Anca | Negru, Anca | Catana, Remulus | Diaconu, Ioan | Tilișcan, Cătălin | Aramă, Victoria | Aramă, Sorin Ștefan | Pavlovia, Ivana Pesic | Salemovic, Dubravka | Ranin, Jovan | Jevtovic, Djordje | Roșca, Ovidiu | Ardeleanu, Andreea | Caramangiu, Iulia | Desaga, Daniela | Bică, Valerica | Mitrescu, Sorina | Marincu, Iosif | Siljic, Marina | Salemovic, Dubravka | Nikolic, Valentina | Jevtovic, Djordje | Pesic-Pavlovic, Ivana | Ranin, Jovan | Todorovic, Marija | Stanojevic, Maja | Șincu, Nina-Ioana | Georgescu, Anca | Țilea, Brândușa | Kezdi, Iringo Zaharia | Incze, Andrea | Gârbovan, Cristina | Chiriac, Carmen Lucia | Luca, Anca Elena | Lazăr, Florin | Luca, Adrian | Ene, Luminița | Rădoi, Roxana | Talnariu, Adina | Suciu, Silvia | Achim, Cristian | Iacob, Diana Gabriela | Florea, Dragoș | Iacob, Simona | Arbune, Manuela | Drăgănescu, Miruna | Iancu, Alina | Moroti, Ruxandra | Niculae, Cristian M. | Merisor, Simona | Manea, Eliza | Benea, Serban | Stan, Andrada | Hrisca, Raluca | Jipa, Raluca | Tanase, Diana | Hristea, Adriana | Grgic, Ivana | Planinic, Ana | Gorenec, Lana | Lepej, Snjezana Zidovec | Vince, Adriana
BMC Infectious Diseases  2016;16(Suppl 3):290.
O1 HIV-1 diversity in Bulgaria (current molecular epidemiological picture)
Ivailo Alexiev, Reneta Dimitrova, Anna Gancheva, Asya Kostadinova, Mariyana Stoycheva, Daniela Nikolova, Ivaylo Elenkov
O2 Knowledge, attitudes and practices of the general population on HIV/AIDS, hepatitis B and C in Romania
Cătălin Tilișcan, Mioara Predescu, Bogdan Păunescu, Anca Streinu-Cercel, Oana Săndulescu, Claudiu Mihai Șchiopu, Mădălina Hristache, Lăcrămioara Aurelia Brîndușe, Adrian Streinu-Cercel
O3 The prevalence of human leukocyte antigen-B*57:01 allele carriers and CXCR4 tropism among newly diagnosed HIV infected patients in Serbia
Marija Todorovic, Marina Siljic, Dubravka Salemovic, Valentina Nikolic, Ivana Pesic-Pavlovic, Jovan Ranin, Djordje Jevtovic, Maja Stanojevic
O4 HIV transmission among stable serodiscordant couples from the former Pediatric Cohort follow up in the National Institute of Infectious Diseases
Ana Maria Tudor, Delia Vlad, Mariana Mărdărescu, Sorin Petrea, Cristina Petre, Ruxandra Neagu-Drăghicenoiu, Rodica Ungurianu, Alina Cibea, Odette Chirilă, Cristian Anghelina, Ileana Coserea
O5 Unemployment is associated with syringe sharing among people who inject drugs in Greece
Pantelia-Amalia Krikelli, Eirini Pavlitina, Mina Psichogiou, Demetris Lamnisos, Leslie Williams, Anya Korobchuk, Britt Skaathun, Pavlo Smyrnov, John Schneider, Vana Sypsa, Dimitrios Paraskevis, Angelos Hatzakis, Samuel R. Friedman, Georgios K. Nikolopoulos
O6 Correlation of adipocytokine levels in different types of lipodystrophy in HIV/AIDS patients
Gordana Dragović, Danica Srdić, Al Musalhi Khawla, Ivan Soldatović, Jelena Nikolić, Djordje Jevtović, Devaki Nair
O7 IP10 – a possible biomarker for the progression of HIV infection
Aura Temereanca, Adelina Rosca, Luminita Ene, Benchawa Soontornniyomkij, Carmen Diaconu, Claudia Dita, Cristian Achim, Simona Ruta
O8 A permanent challenge: persistent low viremia in HIV positive patients on ART
Șerban Benea, Ruxandra Moroti, Raluca Jipa, Eliza Manea, Andrada Stan, Elisabeta Benea, Dan Oțelea, Adriana Hristea
O9 Infections in IDUs according to their HIV status
Adriana Hristea, Irina Lăpădat, Raluca Jipa, Ruxandra Moroti, Șerban Benea, Doina Antonică, Irina Panait, Roxana Petre
O10 Trends in combined antiretroviral therapy used in methadone program integrated with HIV care - 20 years of experience
Justyna D. Kowalska, Ewa Pietraszkiewicz, Ewa Grycner, Ewa Firlag-Burkacka, Andrzej Horban
O11 Extracellular cyclophilin A – inflammatory mediator in HIV infected patients
Ovidiu Vlaicu, Leontina Bănică, Simona Paraschiv, Ana-Maria Tudor, Ruxandra Moroti, Dan Oțelea
O12 High cardiovascular disease risk in Serbian population, an issue of concern
Bojana Dimitrijević, Ivan Soldatović, Đorđe Jevtović, Jovana Kusić, Dubravka Salemović, Jovan Ranin, Gordana Dragović
O13 Genotypic rifampicin resistance in HIV/ tuberculosis coinfected patients from a tertiary level infectious diseases hospital
Dragoș Florea, Ioana Bădicuț, Alexandru Rafila, Cornel Camburu, Adriana Histrea, Mihaela Frățilă, Dan Oțelea
O14 Occurrence of residual HCV RNA in liver and peripheral blood mononuclear cells among patients with chronic hepatitis C infection and/or HCV/HIV coinfection after IFN-based therapy
Ivana Gmizic, Dubravka Salemovic, Ivana Pesic-Pavlovic, Marina Siljic, Valentina Nikolic, Miljana Djonin-Nenezic, Ivana Milosevic, Branko Brmbolic, Maja Stanojevic
O15 Romanian nationwide screening for infection with HIV and hepatitis B and C viruses
Anca Streinu-Cercel, Oana Săndulescu, Alina Cristina Neguț, Mioara Predescu, Alexandra Mărdărescu, Mihai Săndulescu, Adrian Streinu-Cercel
O16 Treatment emergent variants to combined direct antiviral agents therapy against hepatitis C virus
Ana Belen Pérez, Natalia Chueca, Marta Álvarez, Juan Carlos Alados, Antonio Rivero, Francisco Vera, Marcial Delgado, Javier Salmeron, Miguel Jiménez, Maria José Blanco, Moises Diago, Miguel Garcia-deltoro, Marta Alvarez, Francisco Téllez, Federico García
O17 Clinical and epidemiological aspects in tuberculosis/HIV coinfected patients
Diana Tănase, Eliza Manea, Rodica Bacruban, Dragoș Florea, Dan Oțelea, Alexandru Rafila, Mariana Mărdărescu, Adriana Hristea
O18 Resistance to NS3 protease inhibitors in persons with chronic hepatitis C infected with hepatitis C virus subtype 1a from Croatia
Ivana Grgic, Ana Planinic, Maja Santak, Lana Gorenec, Snjezana Zidovec Lepej, Adriana Vince
O19 Analysis of a simplified diagnostic score for tuberculous meningitis in HIV-infected adults with meningitis
Eliza Manea, Adriana Hristea, Șerban Benea, Ruxandra Moroti, Diana Tănase, Cristian M. Niculae, Simona Merisor, Raluca Jipa
O20 Molecular tracing of the origin of HIV-1 infection among persons who inject drugs in Athens: a phyloethnic study
Dimitrios Paraskevis, Evangelia Kostaki, Georgios K. Nikolopoulos, Vana Sypsa, Mina Psichogiou, Dimitra Paraskeva, Athanassios Skoutelis, Meni Malliori, Samuel R. Friedman, Angelos Hatzakis
O21 The dynamics of virological response to HIV-1 infection and antiretroviral therapy initiation in patients with and without HLA-B*5701 Allele
Malgorzata Hackiewicz, Piotr Zabek, Ewa Firlag-Burkacka, Andrzej Horban, Justyna Dominika Kowalska
O22 Increase in the numbers of non-B subtypes and potential recombinant forms circulating among Slovenian MSM in the recent years
Maja M. Lunar, Jana Mlakar, Mario Poljak
O23 Genotyping intrahost polymorphisms in hepatitis C virus E2 protein associated with resistance to antibody neutralization
Leontina Bănică, Eliza Martin, Valeriu Gheorghiță, Andrei Petrescu, Dan Oțelea, Costin-Ioan Popescu, Simona Paraschiv
O24 Genotyping of HCV NS3 protease inhibitors resistance and phenotyping of rare double resistance mutations in HCV cell culture system
Emil Neaga, Vlaicu Ovidiu, Andrei Juncu, Leontina Bănică, Simona Paraschiv, Dan Oțelea, Costin-Ioan Popescu
O25 Employment status controls the relationship between neurocognitive impairment and depression in a cohort of young HIV-infected adults since childhood
Adrian Luca, Florin Lazăr, Anca Elena Luca, Luminița Ene, Cristian Achim
O26 Predictors of survival in parenterally-infected HIV positive children and youth diagnosed with progressive multifocal leukoencephalopathy
Cosmina Gingăraş, Ștefan Adrian Anton, Roxana Rădoi, Simona Tetradov, Grațiela Țârdei, Maria Nica, Razvan Alexandru Capşa, Cristian L. Achim, Cristiana Oprea, Luminița Ene
O27 Neurocognitive and brain functioning in HIV-infected young MSM treated with cART
Bogna Szymańska, Natalia Gawron, Agnieszka Pluta, Emilia Łojek, Ewa Firląg – Burkacka, Andrzej Horban, Robert Bornstein, et HARMONIA3 Study Group
O28 Clinical value of RT-PCR detection of Toxoplasma gondii DNA in cerebrospinal fluid
Olivia Burcoș, Simona Manuela Erscoiu, Filofteia Bănicioiu Cojanu, Andreea Toderan, Maria Nica, Ionuț Cristian Popa, Emanoil Ceaușu, Petre Iacob Calistru
O29 Characteristics of sleep disorders in Romanian adults infected with human immunodeficiency virus
Manuela Arbune, Mirela Alexandrache, Anca-Adriana Arbune, Doina-Carina Voinescu
O30 Diagnosing neuroHIV: the rift between clinicians and pathologists
Ioan-Alexandru Diaconu, Laurențiu Stratan, Victoria Aramă, Luciana Nichita, Alexandra Diaconu, Anca Negru, Alina Orfanu, Anca Leuștean, Daniela Adriana Ion
O31 A challenging neurological complication in a HIV-infected young woman with multiple opportunistic infections
Irina Ianache, Cristiana Oprea
O32 Brain abscess with uncertain etiology in a late-presenter HIV infected patient
Anca Leuștean, Cristina Popescu, Alina Orfanu, Anca Negru, Remulus Catana, Cristina Murariu, Ioan-Alexandru Diaconu, Mihaela Rădulescu, Cătălin Tilișcan, Victoria Aramă
O33 Cerebral toxoplasmosis and left crural monoparesis with fatal evolution in a noncompliant patient with AIDS C3
Iosif Marincu, Patricia Poptelecan, Valeria Bică, Florin Lazăr, Livius Tirnea
O34 Opportunistic infections still a problem in HIV-infected patients in cART era: a Romanian single center experience
Irina Ianache, Roxana Rădoi, Manuela Nica, Grațiela Țârdei, Luminița Ene, Emanoil Ceaușu, Petre Calistru, Cristiana Oprea
P1: Epidemiological aspects of co-infection of HIV/TB in Moldova
Iurie Osoianu, Ala Halacu
P2 Perinatal exposure at HIV infection in Oltenia region
Andreea Cristina Stoian, Florentina Dumitrescu, Iulian Diaconescu, Augustin Cupșa, Lucian Giubelan, Loredana Ionescu, Irina Niculescu
P3 Women living with HIV in Mureș county
Carmen Chiriac, Nina Șincu, Iringo Zaharia Kezdi, Anca Georgescu, Brândușa Țilea, Cristina Girbovan, Andrea Incze, Andrea Fodor
P4 Late diagnosis of HIV infection in children - a challenge for Romania
Alina Cibea, Mariana Mărdărescu, Cristina Petre, Ruxandra Drăghicenoiu, Rodica Ungurianu, Ana Maria Tudor, Delia Vlad, Carina Matei
P5 Cirrhosis Assessment in Patients Co-infected HIV-Hepatitis B Virus
Elena Dumea, Lucian Cristian Petcu, Simona Claudia Cambrea
P6 HIV late presenters in Craiova Regional Center, Romania
Florentina Dumitrescu, Augustin Cupsa, Andreea Cristina Stoian, Lucian Giubelan, Irina Niculescu, Iulian Diaconescu, Dan Hurezeanu, Livia Dragonu, Mioara Cotulbea
P7 Some aspects of malignancies in patients HIV / AIDS
Simona Manuela Erscoiu, Ionuț Cristian Popa, Denisa Stroie, Petronela Ionescu, Nedeea Duță, Camelia Dobrea, Irina Voican, Emanoil Ceaușu, Petre Iacob Calistru
P8 Factors associated with resilience among people living with HIV in Romania
Florin Lazăr
P9 Fever in HIV-infected patients: a thorny problem to be solved by the clinicians
Lucian Giubelan, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Dan Hurezeanu, Livia Dragonu, Irina Niculescu, Andreea Cristina Stoian, Oana Obretin, Mariana Stănescu, Mihai Jianu
P10 Th1, Th2, Th9, Th17 and Th22 cytokines in acute and chronic HIV-1 infection
Lana Gorenec, Snjezana Zidovec Lepej, Ivana Grgic, Ana Planinic, Janja Iscic Bes, Adriana Vince, Josip Begovac
P11 Dyslipidemia in HIV-infected patients treated with protease inhibitors – case report
Luminița Elena Horga
P12 Why use less treatment for the metabolic abnormalities in HIV patients-too many drugs?
Corina Itu, Luminița Elena Horga, Laura Augusta David-Aldea, Anca Ciorogar, Cristian Jianu, Mihaela Lupșe
P13 Sacral Herpes Zoster, with hyperalgesic form, in a patient with C3 stage HIV infection
Iuliana Caramangiu, Ovidiu Roșca, Monica Cialma, Andreea Ardeleanu, Iosif Marincu
P14 Factors associated with in-hospital mortality in tuberculous and cryptococcal meningitis
Raluca Jipa, Eliza Manea, Șerban Benea, Irina Lăpădat, Nicoleta Irimescu, Irina Panait, Cristian Niculae, Adriana Hristea
P15 Lipodystrophy: still present adverse event in resource-limited settings
Jovana Kusic, Djordje Jevtovic, Dubravka Salemovic, Jovan Ranin, Bozana Dimitrijevic, Gordana Dragovic
P16 TB and HIV coinfected patient, an emergent challenge - case report
Laura-Augusta Aldea-David
P17 Efficacy of prophylactic antiretroviral treatment in new-born infants from HIV-positive mothers in 2012-2014, for the North-Eastern part of Romania
Carmen Manciuc, Cristina Nicolau, Liviu Prisăcariu, Alexandra Largu
P18 Surveillance of mother to child transmission of HIV in Romania – 31 December 2015
Mariana Mărdărescu, Adrian Streinu-Cercel, Cristina Petre, Marieta Iancu, Sanda Vintilă, Daniela Vitelaru, Iosif Ionel, Claudiu Mihai Șchiopu, Alexandra-Henriette Mărdărescu
P19 The antiretroviral therapy failure and the need to select the effective treatment in the Republic of Moldova
Pavel Micsanschi, Tiberiu Holban, Ina Bîstrițchi, Lucia Pârțână, Angela Nagîț, Svetlana Popovici, Maria Talmaci, Irina Cucerova
P20 Disseminated cryptococcosis in a patient with C3 HIV stage and multiresistant to antiretroviral therapy with lethal evolution
Sorina Georgiana Mitrescu, Dana Mihalcea, Iulia Caramangiu, Ovidiu Roșca, Iosif Maricu
P21 Aspects of tuberculosis infection in HIV-positive patients from Romania – our experience
Anca Negru, Daniela Munteanu, Victoria Aramă, Raluca Mihăilescu, Ioan Diaconu, Remulus Catana, Cristina Popescu, Alina Orfanu, Anca Leuștean, Mihaela Rădulescu, Cătălin Tilișcan, Raluca Năstase, Violeta Molagic, Irina Duport, Cristina Dragomirescu, Ștefan Sorin Aramă
P22 Dyslipidemia in HIV-infected patients
Nicoleta M Negruț
P23 Challenges in the management of an HIV seropositive patient with psoriasis undergoing immunomodulator therapy
Violeta Elena Niță, Daniela Ioana Munteanu, Raluca Mihăilescu, Ioan Diaconu, Anca Negru, Cristina Popescu, Victoria Aramă
P24 Acute peritonitis as a sign of IRIS in an HIV-infected patient with MAC latent infection
Alina Orfanu, Cristina Popescu, Anca Leuștean, Anca Negru, Remulus Catana, Ioan Diaconu, Cătălin Tilișcan, Victoria Aramă, Sorin Ștefan Aramă
P25 The virologic outcome of the treatment of chronic hepatitis B among HIV co-infected patients on HAART
Ivana Pesic Pavlovia, Dubravka Salemovic, Jovan Ranin, Djordje Jevtovic
P26 A case of HIV encephalopathy with aphasia, agnosia, apraxia and right homonymous hemianopsia
Ovidiu Roșca, Andreea Ardeleanu, Iulia Caramangiu, Daniela Desaga, Valerica Bică, Sorina Mitrescu, Iosif Marincu
P27 Molecular footprints on human immunodeficiency virus -1 genome and association with phylogenetic clustering among subtype B infected patients in Serbia
Marina Siljic, Dubravka Salemovic, Valentina Nikolic, Djordje Jevtovic, Ivana Pesic-Pavlovic, Jovan Ranin, Marija Todorovic , Maja Stanojevic
P28 Neurosyphilis and human immunodeficiency virus infection: double challenge
Nina-Ioana Șincu, Anca Georgescu, Brândușa Țilea, Iringo Zaharia Kezdi, Andrea Incze, Cristina Gârbovan, Carmen Lucia Chiriac
P29 Differences between HIV-infected adults since childhood and non HIV-infected persons on managing everyday life
Anca Elena Luca, Florin Lazăr, Adrian Luca, Luminița Ene, Roxana Rădoi, Adina Talnariu, Silvia Suciu, Cristian Achim
P30 Molecular detection of Bartonella quintana in a HIV immunodepressed patient with fever and isolated lymphadenopathy - Case report
Diana Gabriela Iacob, Dragoș Florea, Simona Iacob
P31 Present epidemiological characteristics of HIV/AIDS newly diagnosed cases in South-Eastern Romania
Manuela Arbune, Miruna Drăgănescu, Alina Iancu
P32 The gender’s preferences among opportunists?
Ruxandra Moroti, Cristian M Niculae, Simona Merisor, Eliza Manea, Serban Benea, Andrada Stan, Raluca Hrisca, Raluca Jipa, Diana Tanase, Adriana Hristea
P33 Polymorphism of interleukin-28B gene in persons with chronic hepatitis C from Croatia
Ivana Grgic, Ana Planinic, Lana Gorenec, Snjezana Zidovec Lepej, Adriana Vince
PMCID: PMC4928154  PMID: 27356504
8.  IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study 
PLoS Medicine  2011;8(9):e1001092.
Vijayaprakash Suppiah and colleagues show that genotyping hepatitis C patients for the IL28B, HLA-C, and KIR genes improves the ability to predict whether or not patients will respond to antiviral treatment.
To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%–50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.
Methods and Findings
We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 “G” was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10−8, 1.67–2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10−14, 2.67–5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05–2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10−6, 2.03–7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.
Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B.
Please see later in the article for the Editors' Summary
Editors' Summary
About 170 million people harbor long-term (chronic) infections with the hepatitis C virus (HCV) and 3–4 million people are newly infected with the virus every year. HCV—a leading cause of chronic hepatitis (inflammation of the liver)—is spread though contact with infected blood. Transmission can occur during medical procedures (for example, transfusions with unscreened blood or reuse of inadequately sterilized medical instruments) but in developed countries, where donated blood is routinely screened for HCV, the most common transmission route is needle-sharing among intravenous drug users. HCV infection can cause a short-lived illness characterized by tiredness and jaundice (yellow skin and eyes) but 70%–80% of newly infected people progress to a symptom-free, chronic infection that can eventually cause liver cirrhosis (scarring) and liver cancer. HCV infections can be treated with a combination of two drugs—pegylated interferon-alpha and ribavirin (PegIFN/R). However, PegIFN/R is expensive, causes unpleasant side-effects, and is ineffective in about half of people infected with HCV genotype 1, the commonest HCV strain.
Why Was This Study Done?
It would be extremely helpful to be able to identify which patients will respond to PegIFN/R before starting treatment. An individual's genetic make-up plays a key role in the safety and effectiveness of drugs. Thus, pharmacogenomics—the study of how genetic variants affects the body's response to drugs—has the potential to alter the clinical management of many diseases by allowing clinicians to provide individually tailored drug treatments. In 2009, scientists reported that certain single nucleotide polymorphisms (SNPs, a type of genetic variant) lying near the IL28B gene (which encodes an immune system protein made in response to viral infections) strongly influence treatment outcomes and spontaneous clearance in HCV-infected people. This discovery is now being used to predict treatment responses to PegIFN/R in clinical practice but genotyping (analysis of variants of) IL28B only correctly predicts treatment failure two-thirds of the time. Here, the researchers investigate whether genotyping two additional regions of the genome—the HLA-C and KIR gene loci—can improve the predictive value of IL28B genotyping. Human leukocyte antigen C (HLA-C) and the killer immunoglobulin-like receptors (KIRs) are interacting proteins that have been implicated in HCV viral control.
What Did the Researchers Do and Find?
The researchers genotyped 417 patients chronically infected with HCV genotype 1 whose infection had been cleared by PegIFN/R treatment, 493 patients whose infection had not responded to treatment, and 234 patients whose infection had cleared spontaneously for two HLA-C variants (C1 and C2), the presence of several KIR genes (individuals carry different combinations of KIR genes), and two IL28B SNPs (rs8099917 and rs12979860). Carriage of “variants” of either IL28B SNP was associated with absence of treatment-induced clearance and absence of spontaneous clearance. That is, these variant SNPs were found more often in patients who did not respond to treatment than in those who did respond, and more often in patients who did not have spontaneous clearance of their infection than those who did. The HLA-C C2C2 genotype (there are two copies of most genes in the genome) was also more common in patients who failed treatment than in those who responded but was not associated with spontaneous clearance. The rate of correct prediction of treatment failure increased from 66% with IL28B genotyping alone to 80% with combined IL28B and HLA-C genotyping. Finally, carriage of specific KIR genes in combination with specific HLA-C and IL28B variants was also associated with an altered HCV treatment response.
What Do These Findings Mean?
These findings show that the addition of HCL-C and KIR genotyping to IL28B genotyping improved the prediction of HCV treatment response in the patients investigated in this study. Because all these patients were European or of European descent, these findings need confirming in people of other ethnic backgrounds. They also need confirming in other groups of Europeans before being used in a clinical setting. However, the discovery that the addition of HLA-C genotyping to IL28B genotyping raises the rate of correct prediction of PegIFN/R treatment failure to 80% is extremely promising and should improve the clinical management of patients infected with HCV genotype 1. In addition, these results provide new insights into how PegIFN/R clears HCV infections that may lead to improved therapies in the future.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides detailed information about hepatitis C (in several languages)
The US Centers for Disease Control and Prevention provides information on hepatitis C for the public and for health professionals (information is also available in Spanish)
The US National Institute of Diabetes and Digestive and Kidney Diseases provides basic information on hepatitis C (in English and Spanish)
The Hepatitis C Trust is a patient-led, patient-run UK charity that provides detailed information about hepatitis C and support for patients and their families; a selection of personal stories about patients' experiences with hepatitis C is available, including Phil's treatment story, which details the ups and downs of treatment with PegIFN/R
MedlinePlus provides links to further resources on hepatitis C
The Human Genome Project provides information about medicine and the new genetics, including a primer on pharmacogenomics
PMCID: PMC3172251  PMID: 21931540
AIDS (London, England)  2011;25(4):513-518.
To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. Here we perform a genome-wide association study (GWAS) in a population of 1,532 individuals from Malawi, a country with high prevalence of HIV-1 infection, to investigate whether common genetic variants associate with HIV-1 susceptibility in Africans. Using single nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing.
After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P-value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk ≥ 2.0 and minor allele frequencies ≥12%. This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to non-genetic parameters or to complex interactions between genes, immunity and environment.
PMCID: PMC3150594  PMID: 21160409
Human immunodeficiency virus (HIV-1); acquisition; resistance; Genome Wide Association Study (GWAS); Africa
10.  Association of Polymorphisms in the LEDGF/p75 Gene (PSIP1) with Susceptibility to HIV-1 Infection and Disease Progression 
AIDS (London, England)  2011;25(14):1711-1719.
LEDGF/p75, encoded by the PSIP1 gene, interacts with HIV-1 integrase and targets HIV-1 integration into active genes. We investigated the influence of polymorphisms in PSIP1 on HIV-1 acquisition and disease progression in black South Africans.
Integrase binding domain (IBD) of LEDGF/p75 was sequenced in 126 participants. Four haplotype tagging SNPs, SNP1-SNP4 and one exonic SNP, SNP5 were genotyped in 195 HIV-1 seronegative, 52 primary and 403 chronically infected individuals using TaqMan assays. LEDGF/p75 expression was quantified by real-time RT-PCR. The impact of Q472L mutation on the interaction with HIV-1 IN was measured by AlphaScreen.
rs2277191A was more frequent among seropositives (p=0.06, Fisher's exact test), and among individuals followed longitudinally trended towards association with higher likelihood of HIV-1 acquisition (RH=2.21, p=0.08; Cox model) and it was also associated with rapid disease progression (RH=5.98, p=0.04; Cox model). rs12339417C was associated with slower decline of CD4+ T cell (p=0.02) and lower levels of LEDGF/p75 (p<0.01). Seroconverters had higher preinfection levels of LEDGF/p75 (p<0.01) but levels decreased after HIV infection (p=0.02).
Genetic variants of PSIP1 may affect HIV-1 outcomes. Further studies are needed to confirm the effect of genetic variation of PSIP1 on HIV-1 pathogenesis in different cohorts.
PMCID: PMC3233670  PMID: 21681054
11.  Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples 
PLoS Medicine  2012;9(6):e1001251.
In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital tract of HIV-1–infected women. However, whether BV, which is present in up to half of African HIV-1–infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
Methods and Findings
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1–seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1–seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7–10 and 0–3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1–infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1–infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74–7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37–7.33).
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥250 cells/mm3 and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1–infected women could mitigate female-to-male HIV-1 transmission.
Trial Registration: NCT00194519
Please see later in the article for the Editors' Summary
Editors' Summary
Since the first reported case of AIDS in 1981, the number of people infected with HIV, the virus that causes AIDS, has risen steadily. By the end of 2010, 34 million people were living with HIV/AIDS. At the beginning of the epidemic more men than women were infected with HIV. Now, however, 50% of all adults infected with HIV are women and in sub-Saharan Africa, where two-thirds of HIV-positive people live, women account for 59% of people living with HIV. Moreover, among 15–24 year-olds, women are eight times more likely than men to be HIV-positive. This pattern of infection has developed because most people in sub-Saharan Africa contract HIV through unprotected heterosexual sex. The risk of HIV transmission for both men and women in Africa and elsewhere can be reduced by abstaining from sex, by only having one or a few partners, by always using condoms, and by male circumcision. In addition, several studies suggest that antiretroviral therapy (ART) greatly reduces HIV transmission.
Why Was This Study Done?
Unfortunately, in sub-Saharan Africa, only about a fifth of HIV-positive people are currently receiving ART, which means that there is an urgent need to find other effective ways to reduce HIV transmission in this region. In this prospective cohort study (a type of study that follows a group of people for some time to see which personal characteristics are associated with disease development), the researchers investigate whether bacterial vaginosis—a condition in which harmful bacteria disrupt the normal vaginal flora—increases the risk of female-to-male HIV transmission among African couples. Bacterial vaginosis, which is extremely common in sub-Saharan Africa, has been associated with an increased risk of HIV acquisition in women and induces viral replication and shedding in the vagina in HIV-positive women, which may mean that HIV-positive women with bacterial vaginosis are more likely to transmit HIV to their male partners than women without this condition. If this is the case, then interventions that reduce the incidence of bacterial vaginosis might be valuable HIV prevention strategies.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 2,236 heterosexual African couples enrolled in a clinical trial (the Partners in Prevention HSV/HIV Transmission Study) whose primary aim was to investigate whether suppression of herpes simplex virus infection could prevent HIV transmission. In all the couples, the woman was HIV-positive and the man was initially HIV-negative. The female partners were examined every three months for the presence of bacterial vaginosis and the male partners were tested regularly for HIV infection. The researchers also determined whether the men who became HIV-positive were infected with the same HIV strain as their partner to check that their infection had been acquired from this partner. The HIV incidence in men whose partners had bacterial vaginosis was 2.9 per 100 person-years (that is, 2.9 out of every 100 men became HIV-positive per year) whereas the HIV incidence in men whose partners had a normal vaginal flora was 0.76 per 100 person-years. After controlling for factors that might affect the risk of HIV transmission such as male circumcision and viral levels in female partner's blood, the researchers estimated that bacterial vaginosis was associated with a 3.17-fold increased risk of female-to-male HIV transmission in their study population.
What Do These Findings Mean?
These findings suggest that HIV-positive African women with bacterial vaginosis are more than three times as likely to transmit HIV to their male partners as those with a normal vaginal flora. It is possible that some unknown characteristic of the men in this study might have increased both their own risk of HIV infection and their partner's risk of bacterial vaginosis. Nevertheless, because bacterial vaginosis is so common in Africa (half of the women in this study had bacterial vaginosis at least once during follow-up) and because this condition is associated with both female HIV acquisition and transmission, these findings suggest that bacterial vaginosis could be responsible for a substantial proportion of new HIV infections in Africa. Normalization of vaginal flora in HIV-infected women by frequent presumptive treatment with antimicrobials (treatment with a curative dose of antibiotics without testing for bacterial vaginosis) or possibly by treatment with probiotics (live “good” bacteria) might, therefore, reduce female-to-male HIV transmission in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS and on bacterial vaginosis
The US Centers for Disease Control and Prevention has information on all aspects of HIV/AIDS, including specific information about HIV/AIDS and women; it also has information on bacterial vaginosis (in English and Spanish)
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment, and information on bacterial vaginosis and HIV transmission (in several languages)
Information is available from Avert, an international AIDS nonprofit group on many aspects of HIV/AIDS, including detailed information on HIV and AIDS prevention, on women, HIV and AIDS and on HIV/AIDS in Africa (in English and Spanish); personal stories of women living with HIV are available; the website Healthtalkonline also provides personal stories about living with HIV
More information about the Partners in Prevention HSV/HIV Transmission Study is available
PMCID: PMC3383741  PMID: 22745608
12.  Impact of Antiretroviral Therapy on Incidence of Pregnancy among HIV-Infected Women in Sub-Saharan Africa: A Cohort Study 
PLoS Medicine  2010;7(2):e1000229.
A multicountry cohort study in sub-Saharan Africa by Landon Myer and colleagues reveals higher pregnancy rates in HIV-infected women on antiretroviral therapy (ART).
With the rapid expansion of antiretroviral therapy (ART) services in sub-Saharan Africa there is growing recognition of the importance of fertility and childbearing among HIV-infected women. However there are few data on whether ART initiation influences pregnancy rates.
Methods and Findings
We analyzed data from the Mother-to-Child Transmission-Plus (MTCT-Plus) Initiative, a multicountry HIV care and treatment program for women, children, and families. From 11 programs in seven African countries, women were enrolled into care regardless of HIV disease stage and followed at regular intervals; ART was initiated according to national guidelines on the basis of immunological and/or clinical criteria. Standardized forms were used to collect sociodemographic and clinical data, including incident pregnancies. Overall 589 incident pregnancies were observed among the 4,531 women included in this analysis (pregnancy incidence, 7.8/100 person-years [PY]). The rate of new pregnancies was significantly higher among women receiving ART (9.0/100 PY) compared to women not on ART (6.5/100 PY) (adjusted hazard ratio, 1.74; 95% confidence interval, 1.19–2.54). Other factors independently associated with increased risk of incident pregnancy included younger age, lower educational attainment, being married or cohabiting, having a male partner enrolled into the program, failure to use nonbarrier contraception, and higher CD4 cell counts.
ART use is associated with significantly higher pregnancy rates among HIV-infected women in sub-Saharan Africa. While the possible behavioral or biomedical mechanisms that may underlie this association require further investigation, these data highlight the importance of pregnancy planning and management as a critical but neglected component of HIV care and treatment services.
Please see later in the article for the Editors' Summary
Editors' Summary
Human immunodeficiency virus (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which is a major global cause of disease and death. More than 33 million people around the world are infected with HIV, with nearly 5,500 dying daily from HIV and AIDS-related complications. HIV/AIDS is especially problematic in sub-Saharan Africa, where it is the leading cause of death. There is no cure for HIV/AIDS, but medicines known as “antiretroviral therapy” (ART) can prolong life and reduce complications in patients infected with HIV. 97% of patients with HIV/AIDS live in low- and middle-income countries. According to the World Health Organization, nearly 10 million of these patients need ART. As patients' access to treatment is often hindered by the high cost and low availability of ART, global health efforts have focused on promoting ART use in resource-limited nations. Such efforts also increase awareness of how HIV is spread (contact with blood or semen, in sexual intercourse, sharing needles, or from mother to child during childbirth). ART reduces, but does not remove, the chance of a mother's passing HIV to her child during birth.
Why Was This Study Done?
By the end of 2007, 3 million HIV-infected patients in poor countries were receiving ART. Many of those treated with ART are young women of child-bearing age. Childbirth is an important means of spreading HIV in sub-Saharan Africa, where 60% of all HIV patients are women. This study questions whether the improved health and life expectancy that results from treatment with ART affects pregnancy rates of HIV-infected patients. The study explores this question in seven African countries, by examining the rates of pregnancy in HIV-infected women before and after they started ART.
What Did the Researchers Do and Find?
The authors looked at the records of 4,531 HIV-infected women enrolled in the Mother-to-Child-Transmission-Plus (MTCT-Plus) Initiative in seven African countries. MTCT -Plus, begun in 2002, is a family-centered treatment program that offers regular checkups, blood tests, counseling, and ART treatment (if appropriate) to women and their families. At each checkup, women's CD4+ cell counts and World Health Organization guidelines were used to determine their eligibility for starting ART. Over a 4-year period, nearly a third of the women starting ART experienced a pregnancy: 244 pregnancies occurred in the “pre-ART” group (women not receiving ART) compared to 345 pregnancies in the “on-ART” group (women receiving ART). The chance of pregnancy increased over time in the on-ART group to almost 80% greater than the pre-ART group, while remaining relatively low and constant in the pre-ART group. The authors noted that, as expected, other factors also increased the chances of pregnancy, including younger age, lower educational status, and use of nonbarrier contraception such as injectable hormones.
What Do These Findings Mean?
This study suggests that starting ART is associated with higher pregnancy rates in sub-Saharan Africa, nearly doubling the chances of a woman becoming pregnant. The reasons for this link are unclear. One possible explanation is behavioral: women receiving ART may feel more motivated to have children as their health and quality of life improve. However, the study did not examine how pregnancy desires and sexual activity of women changed while on ART, and cannot discern why ART is linked to increased pregnancy. By using pregnancy data gathered from patient questionnaires rather than laboratory tests, the study is limited by the possibility of inaccurate patient reporting. Understanding how pregnancy rates vary in HIV-infected women receiving ART helps support the formation of responsive, effective HIV programs. Female HIV patients of child-bearing age, who form the majority of patients receiving ART in sub-Saharan Africa, would benefit from programs that combine starting HIV treatment with ART with education and contraception counseling and pregnancy-related care.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
A UNAIDS 2008 report is available on the global AIDS epidemic
The International Planned Parenthood Foundation provides information on sexual and reproductive health and HIV
The International Center for AIDS Care and Treatment Programs at the Columbia University Mailman School of Public health provides information to assist HIV care and treatment programs in resource-limited settings
PMCID: PMC2817715  PMID: 20161723
13.  Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa 
PLoS Medicine  2015;12(11):e1001900.
Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.
Methods and Findings
Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.
These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells.
An analysis from a cohort in South Africa reveals how the HIV virus may escape NK cell immunity by acquiring mutations in HLA-mediated epitopes, which affect binding to NK cell receptors.
Editors' Summary
Throughout life, our immune system—a complex network of cells, tissues, and organs—protects us from attack by viruses, bacteria, parasites, and fungi. The body’s first line of defense against these “pathogens” is the innate immune system, a collection of cells and proteins that is always ready to identify and kill a wide range of foreign invaders. As well as directly killing pathogens, the innate immune system activates the adaptive immune response, which recognizes and kills specific pathogens and is responsible for immunological memory. Most pathogens are dispatched quickly and effectively by the two arms of the immune system, but some infectious agents have found ways to evade the immune response. For example, infection with HIV-1, the virus that causes AIDS, results in prolonged, continuous viral replication even though the human body mounts a vigorous HIV-1-specific immune response. In large part, HIV-1’s evasion of the immune response reflects its ability to kill virus-specific CD4 lymphocytes, which are needed to help other immune system cells kill HIV-1-infected cells. In addition, the proteins on the surface of HIV-1 that are recognized by the human immune system (viral antigens) frequently acquire changes (mutations) that make it harder for the immune system to clear HIV-1 from the human body.
Why Was This Study Done?
Viruses evade immune surveillance in many ways, and if we understood the mechanisms underlying immune evasion better, it might be possible to develop targeted immune interventions to deal with viruses such as HIV-1. Here, the researchers investigate how natural killer (NK) cells, a type of lymphocyte that is an important component of the innate antiviral immune response, recognize HIV-infected cells and how HIV-1 evades NK-cell-mediated immune pressure. NK cell activation is determined by the integration of inhibitory and activating signals delivered to the cells by several different receptor families, including the family of killer-cell immunoglobulin-like receptors (KIRs). KIRs mainly bind to human leukocyte antigen (HLA) class I molecules (ligands) on their target cells. HLA class I proteins display fragments (epitopes; peptides recognized by the immune system) of pathogens present in infected cells on the cell surface so that the immune system knows that that cell needs destroying. The binding of distinct KIRs to HLA class I ligands depends on both the sequence of the HLA class I molecule and the sequence of the epitope presented by that HLA class I molecule. Thus, the researchers hypothesized that HIV-1 might evade NK-cell-mediated immune surveillance by acquiring mutations within epitopes presented by HLA class I molecules that enhance the engagement of inhibitory KIRs on NK cells, thereby inhibiting NK cell activity.
What Did the Researchers Do and Find?
To investigate this model, the researchers asked whether any polymorphisms (naturally occurring genetic variations) in the HIV-1 gene encoding the p24 Gag protein were selected on a population level in HIV-1-infected individuals expressing specific combinations of KIRs and HLA class I ligands. Using statistical methods to identify KIR/HLA combined genotypes in a large group of untreated HIV-1-infected individuals from South Africa, they showed that a specific sequence polymorphism in p24 Gag was selected for in individuals expressing both HLA-C*03:04 and KIR2DL3. Functional studies showed that the selection of this variant HIV-1 epitope resulted in better binding of KIR2DL3, an inhibitory KIR, to HLA-C*03:04 than the wild-type epitope. Moreover, the activation of KIR2DL3-positive NK cells from healthy donors in response to HLA-C*03:04-positive target cells presenting the variant epitope was significantly reduced compared to the activation of KIR2DL3-positive NK cells in response to target cells presenting the wild-type epitope.
What Do These Findings Mean?
Further studies are needed to assess the consequences of this and other viral sequence variants for viral fitness, the processing and presentation of the mutant epitope during natural infections, and the control of HIV-1 replication in patients. However, these findings provide new insights into how HIV-1 (and possibly other viruses that have a high mutation rate) might evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance the binding of inhibitory KIRs to HLA class I/peptide complexes. A better understanding of this molecular mechanism for evasion of immune surveillance should facilitate the development of targeted immune interventions (for example, the use of KIR-blocking antibodies, some of which are already being clinically tested for the treatment of cancer) to maximize the antiviral activities of NK cells.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at
The US National Institute of Allergy and Infectious Diseases provides a simple description of the human immune system and information on all aspects of HIV infection and AIDS
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS; Avert also provides personal stories about living with HIV/AIDS
The British Society for Immunology provides short articles about various aspects of immunology, including general information about host–pathogen interactions and immune evasion and specific information about HIV and immune evasion
Wikipedia has pages on natural killer cells, KIRs, and HLA molecules (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC4648589  PMID: 26575988
14.  Causes of Acute Hospitalization in Adolescence: Burden and Spectrum of HIV-Related Morbidity in a Country with an Early-Onset and Severe HIV Epidemic: A Prospective Survey 
PLoS Medicine  2010;7(2):e1000178.
Rashida Ferrand and colleagues show that HIV infection is the commonest cause of hospitalization among adolescents in a high HIV prevalence setting.
Survival to older childhood with untreated, vertically acquired HIV infection, which was previously considered extremely unusual, is increasingly well described. However, the overall impact on adolescent health in settings with high HIV seroprevalence has not previously been investigated.
Methods and Findings
Adolescents (aged 10–18 y) systematically recruited from acute admissions to the two public hospitals in Harare, Zimbabwe, answered a questionnaire and underwent standard investigations including HIV testing, with consent. Pre-set case-definitions defined cause of admission and underlying chronic conditions. Participation was 94%. 139 (46%) of 301 participants were HIV-positive (median age of diagnosis 12 y: interquartile range [IQR] 11–14 y), median CD4 count = 151; IQR 57–328 cells/µl), but only four (1.3%) were herpes simplex virus-2 (HSV-2) positive. Age (median 13 y: IQR 11–16 y) and sex (57% male) did not differ by HIV status, but HIV-infected participants were significantly more likely to be stunted (z-score<−2: 52% versus 23%, p<0.001), have pubertal delay (15% versus 2%, p<0.001), and be maternal orphans or have an HIV-infected mother (73% versus 17%, p<0.001). 69% of HIV-positive and 19% of HIV-negative admissions were for infections, most commonly tuberculosis and pneumonia. 84 (28%) participants had underlying heart, lung, or other chronic diseases. Case fatality rates were significantly higher for HIV-related admissions (22% versus 7%, p<0.001), and significantly associated with advanced HIV, pubertal immaturity, and chronic conditions.
HIV is the commonest cause of adolescent hospitalisation in Harare, mainly due to adult-spectrum opportunistic infections plus a high burden of chronic complications of paediatric HIV/AIDS. Low HSV-2 prevalence and high maternal orphanhood rates provide further evidence of long-term survival following mother-to-child transmission. Better recognition of this growing phenomenon is needed to promote earlier HIV diagnosis and care.
Please see later in the article for the Editors' Summary
Editors' Summary
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV) that causes AIDS. HIV destroys the cells in the immune system that normally provide protection against disease-causing organisms. Consequently, people infected with HIV are susceptible to so-called opportunistic infections, including tuberculosis and pneumonia. HIV is most commonly spread through unprotected sex with an infected partner but another major route of transmission is mother-to-child (vertical transmission) during pregnancy or delivery or during breast feeding. Mother-to-child transmission can be prevented by giving antiviral drugs to HIV-positive mothers during their pregnancy and to their newborn children. But, although most mothers in developed countries have access to this intervention, fewer than half of HIV-positive mothers in low- and middle-income countries receive this treatment and, every year, nearly half a million children become infected with HIV.
Why Was This Study Done?
It is generally thought that HIV infections in infants progress rapidly and that half of the children who acquire HIV from their mothers will die before their second birthday if not treated with antiretroviral drugs. However, as the AIDS epidemic matures, more children are surviving to adolescence with untreated, vertically acquired HIV infection in sub-Saharan Africa, the region where most children with HIV/AIDS live. Little is known about the burden of HIV infection and its contribution to illness and death in adolescents in sub-Saharan Africa but this information is needed to help health care providers prepare for this new aspect of the AIDS epidemic. In this study, the researchers examine the causes of acute hospital admissions (admissions for conditions with a sudden onset and usually a short course) among adolescents in Zimbabwe, a country where the HIV epidemic started early and where one in seven adults is HIV-positive and more than 17,000 children are infected with HIV every year, mainly through vertical transmission.
What Did the Researchers Do and Find?
The researchers recruited 301 10–18-year olds who were admitted to each of the two public hospitals in Harare (Zimbabwe) for acute illnesses between September 2007 and April 2008. Each patient completed a questionnaire about themselves and their health and underwent standard investigations, including HIV testing. Nearly half the participants were HIV positive; about a quarter of these HIV-positive individuals only found out about their status during the study. HIV-positive participants were more likely to be stunted, to have pubertal delay, and to be maternal orphans or have an HIV-infected mother than HIV-negative participants. 69% of HIV-positive participants were admitted to hospital because of infections, often tuberculosis or pneumonia whereas only 19% of the HIV-negative participants were admitted for infections. More than a quarter of all the participants had underlying heart, lung, or other chronic conditions. Finally, 22% of the HIV-positive participants died while in hospital compared to only 7% of the HIV-negative participants. Factors that increased the risk of death among all the participants were advanced HIV infection, pubertal immaturity, and chronic conditions.
What Do These Findings Mean?
These findings indicate that HIV infection is the commonest cause of acute adolescent admission to hospital in Harare (and probably elsewhere in Zimbabwe). Most of these admissions are due to opportunistic infections similar to those seen in HIV-positive adults and to long-term complications of having HIV/AIDS as an infant such as delayed puberty. Other findings indicate that most of the HIV-positive adolescents who participated in this study were infected via vertical transmission, which supports the idea that long-term survival after vertical infection is possible. Because the AIDS epidemic started early in Zimbabwe, there is likely to be a lag before adolescent survivors of vertical HIV transmission become common elsewhere. Nevertheless, all African countries and other places where HIV infection in adults is common need to recognize that the burden of HIV in their acutely unwell adolescents is likely to increase over the next few years. To deal with this emerging aspect of the AIDS epidemic, measures must be introduced to ensure early diagnosis of HIV in this previously neglected age group so that treatment can be started before HIV-positive adolescents become critically ill.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Glenda Gray
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including a list of articles and other sources of information about the primary care of adolescents with HIV
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV and AIDS in Zimbabwe, and on children, HIV, and AIDS (in English and Spanish)
UNICEF also has information about children and HIV and AIDS (in several languages)
PMCID: PMC2814826  PMID: 20126383
15.  Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study 
PLoS Medicine  2012;9(9):e1001304.
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.
Methods and Findings
Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.
Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.
HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.
Please see later in the article for the Editors' Summary.
Editors' Summary
About 34 million people (most living in low- and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, antiretroviral therapy (ART)—cocktails of drugs that keep HIV in check—became available. For people living in affluent countries, HIV/AIDS became a chronic condition. However, ART was expensive and, for people living in poorer countries, HIV/AIDS remained a fatal illness. In 2003, this situation was declared a global emergency, and governments and international agencies began to implement plans to increase ART coverage in resource-limited countries. Since then, ART programs in these countries have grown rapidly. In South Africa, for example, about 52% of the 3.14 million adults in need of ART were receiving an ART regimen recommended by the World Health Organization by the end of 2010.
Why Was This Study Done?
The outcomes of ART programs in resource-limited countries need to be evaluated thoroughly so that these programs can be optimized. One area of concern to ART providers is that of gender differences in survival among patients receiving treatment. In sub-Saharan Africa, for example, men are more likely to die than women while receiving ART. This gender difference in mortality may arise because men initiating ART in many African ART programs have more advanced HIV disease than women (early ART initiation is associated with better outcomes than late initiation) or because men are more likely to be lost to follow-up than women (failure to continue treatment is associated with death). Other possible explanations for gender differentials in mortality on ART include gender differences in immunologic and virologic responses to treatment (increased numbers of immune system cells and reduced amounts of virus in the blood, respectively). In this multicenter cohort study, the researchers examine the size of, and risk factors for, gender differences in mortality on ART in South Africa by examining data collected from adults starting ART at International Epidemiologic Databases to Evaluate AIDS South Africa (IeDEA-SA) collaboration sites.
What Did the Researchers Do and Find?
The researchers analyzed data collected from 46,201 ART-naïve adults who started ART between 2002 and 2009 in eight IeDEA-SA ART programs. At ART initiation, men had a lower CD4 count on average and were more likely to have advanced HIV disease than women. During the study, after allowing for factors likely to affect mortality such as HIV disease stage at initiation, men on ART had a 31% higher risk of dying than women. Men were more likely to be lost to follow-up than women, but men and women who were lost to follow-up were equally likely to die. Women had a slightly better immunological response to ART than men but virologic suppression was similar in both genders. Importantly, in analyses of mortality limited to individuals who were virologically suppressed at 12 months and to patients who had a good immunological response to ART, men still had a higher risk of death than women. However, the gender differences in mortality on ART were smaller than the gender differences in age-standardized mortality in the HIV-negative South African population.
What Do These Findings Mean?
These analyses show that among South African patients initiating ART between 2002 and 2009, men were more likely to die than women but that this gender difference in mortality on ART cannot be completely explained by gender differences in baseline characteristics, loss to follow-up, or virologic and/or immunologic responses. Instead, the observed gender differences in mortality can best be explained by background gender differences in mortality in the whole South African population. Because substantial amounts of data were missing in this study (for example, HIV disease stage was not available for all the patients), these findings need to be interpreted cautiously. Moreover, similar studies need to be done in other settings to investigate whether they are generalizable to the South African national ART program and to other countries. If confirmed, however, these findings suggest that the root causes of gender differences in mortality on ART may be unrelated to HIV/AIDS or to the characteristics of ART programs.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information on the treatment of HIV/AIDS in South Africa is available from the Southern African HIV Clinicians Society
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV/AIDS treatment and care, and on HIV/AIDS in South Africa (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in several languages); its 2010 ART guidelines can be downloaded
Information about the IeDEA-SA collaboration is available
The Treatment Action Campaign provides information on antiretroviral therapy and South African HIV statistics
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about taking anti-HIV drugs and the challenges of anti-HIV drugs
PMCID: PMC3433409  PMID: 22973181
16.  Dense Genotyping of Immune-Related Loci Identifies Variants Associated with Clearance of HPV among HIV-Positive Women in the HIV Epidemiology Research Study (HERS) 
PLoS ONE  2014;9(6):e99109.
Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p<10−6). A variant (rs1633038) in HLA-G were also significantly associated in African American. Results from this study support associations of immune-related genes, having potential biological mechanism, with differential cervical HR-HPV infection outcomes.
PMCID: PMC4053382  PMID: 24918582
17.  The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study 
PLoS Medicine  2012;9(8):e1001295.
Janet Turan and colleagues examined the role of the perception of women in rural Kenya of HIV-related stigma during pregnancy on their subsequent utilization of maternity services.
Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services.
Methods and Findings
From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88).
Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families.
Please see later in the article for the Editors' Summary.
Editors' Summary
Every year, nearly 350,000 women die from pregnancy- or childbirth-related complications. Almost all these “maternal” deaths occur in developing countries. In sub-Saharan Africa, for example, the maternal mortality ratio (the number of maternal deaths per 100,000 live births) is 500 whereas in industrialized countries it is only 12. Most maternal deaths are caused by hemorrhage (severe bleeding after childbirth), post-delivery infections, obstructed (difficult) labor, and blood pressure disorders during pregnancy. All these conditions can be prevented if women have access to adequate reproductive health services and if trained health care workers are present during delivery. Notably, in sub-Saharan Africa, infection with HIV (the virus that causes AIDS) is an increasingly important contributor to maternal mortality. HIV infection causes maternal mortality directly by increasing the occurrence of pregnancy complications and indirectly by increasing the susceptibility of pregnant women to malaria, tuberculosis, and other “opportunistic” infections—HIV-positive individuals are highly susceptible to other infections because HIV destroys the immune system.
Why Was This Study Done?
Although skilled delivery attendants reduce maternal mortality, there are many barriers to their use in developing countries including cost and the need to travel long distances to health facilities. Fears and experiences of HIV-related stigma and discrimination (prejudice, negative attitudes, abuse, and maltreatment directed at people living with HIV) may also be a barrier to the use of skilled childbirth service. Maternity services are prime locations for HIV testing and for the provision of interventions for the prevention of mother-to-child transmission (PMTCT) of HIV, so pregnant women know that they will have to “deal with” the issue of HIV when visiting these services. In this prospective mixed-methods study, the researchers examine the role of pregnant women's perceptions of HIV-related stigma in their subsequent use of maternity services in Nyanza Province, Kenya, a region where 16% women aged 15–49 are HIV-positive and where only 44.2% of mothers give birth in a health facility. A mixed-methods study combines qualitative data—how people feel about an issue—with quantitative data—numerical data about outcomes.
What Did the Researchers Do and Find?
In the Maternity in Migori and AIDS Stigma (MAMAS) study, pregnant women with unknown HIV status living in rural regions of Nyanza Province answered questions about their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal clinic visit. After delivery, the researchers asked the women who tested HIV positive or were not tested for HIV and a sample of HIV-negative women where they had delivered their baby. They also gathered qualitative information about barriers to maternity and HIV service use by interviewing childbearing women, family members, and community health workers. The qualitative data indicate that labor in a health facility is commonly viewed as being most appropriate for women with pregnancy complications such as HIV infection. Thus, women delivering at health facilities risk being labeled as HIV positive, a label that the community associates with promiscuity. The quantitative data indicate that women with more negative attitudes about HIV-positive people (higher perceptions of HIV-related stigma) at baseline were about half as likely to deliver in a health facility with a skilled attendant as women with more positive attitudes about people living with HIV.
What Do These Findings Mean?
These findings suggest that HIV-related stigma is associated with the low rate of delivery by skilled attendants in rural areas of Nyanza Province and possibly in other rural regions of sub-Saharan Africa. Community mobilization efforts aimed at increasing the use of PMTCT services may be partly responsible for the strong perception that delivery in a health facility is most appropriate for women with HIV and other pregnancy complications and may have inadvertently strengthened the perception that women who give birth in such facilities are likely to be HIV positive. The researchers suggest, therefore, that health messages should stress that delivery in a health facility is recommended for all women, not just HIV-positive women or those with pregnancy complications, and that interventions should be introduced to reduce HIV-related stigma. This combined strategy has the potential to increase the use of maternity services by all women and the use of HIV and PMTCT services, thereby reducing some of the most pressing health problems facing women and their children in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at
The United Nations Children's Fund (UNICEF) provides information on maternal mortality, including the WHO/UNICEF/UNFPA/World Bank 2008 country estimates of maternal mortality; a UNICEF special report tells the stories of seven mothers living with HIV in Lesotho
The World Health Organization provides information on maternal health, including information about Millennium Development Goal 5, which aims to reduce maternal mortality (in several languages); the Millennium Development Goals, which were agreed by world leaders in 2000, are designed to eradicate extreme poverty worldwide by 2015
Immpact is a global research initiative for the evaluation of safe motherhood intervention strategies
Maternal Death: The Avoidable Crisis is a briefing paper published by the independent humanitarian medical aid organization Médecins Sans Frontières (MSF) in March 2012
Information is available from Avert, an international AIDS charity on all aspects of HIV/AIDS, including information on women, HIV and AIDS, on HIV and pregnancy, on HIV and AIDS stigma and discrimination, and on HIV in Kenya (in English and Spanish); Avert also has personal stories from women living with HIV
The Stigma Action Network (SAN) is a collaborative endeavor that aims to comprehensively coordinate efforts to develop and expand program, research, and advocacy strategies for reducing HIV stigma worldwide, including mobilizing stakeholders, delivering program and policy solutions, and maximizing investments in HIV programs and services globally
The People Living with Stigma Index aims to address stigma relating to HIV and advocate on key barriers and issues perpetuating stigma; it has recently published Piecing it together for women and girls, the gender dimensions of HIV-related stigma
The Health Policy Project has prepared a review of the academic and programmatic literature on stigma and discrimination as barriers to achievement of global goals for maternal health and the elimination of new child HIV infections (see under Resources)
More information on the MAMAS study is available from the UCSF Center for AIDS Prevention Studies
PMCID: PMC3424253  PMID: 22927800
18.  Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand 
PLoS Medicine  2013;10(8):e1001494.
Using a randomized controlled trial, Marc Lallemant and colleagues ask if a CD4-based monitoring and treatment switching strategy provides a similar clinical outcome compared to the standard viral load-based strategy for adults with HIV in Thailand.
Please see later in the article for the Editors' Summary
Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.
Methods and Findings
The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50–250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6–11.4) in VL versus 7.4% (5.1–10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2–8.4) in VL versus 7.5% (5.0–11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7–19.4) in VL and 24.7 months (15.9–35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8–8.0) in VL versus 15.8 months (8.5–20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.
The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.
Trial registration NCT00162682
Please see later in the article for the Editors' Summary
Editors' Summary
About 34 million people (most of them living in low-and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV infection leads to the destruction of immune system cells (including CD4 cells, a type of white blood cell), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (HAART)—combined drugs regimens that suppress viral replication and allow restoration of the immune system—became available. For people living in affluent countries, HIV/AIDS became a chronic condition but, because HAART was expensive, HIV/AIDS remained a fatal illness for people living in resource-limited countries. In 2003, the international community declared HIV/AIDS a global health emergency and, in 2006, it set the target of achieving universal global access to HAART by 2010. By the end of 2011, 8 million of the estimated 14.8 million people in need of HAART in low- and middle-income countries were receiving treatment.
Why Was This Study Done?
At the time this trial was conceived, national and international recommendations were that HIV-positive individuals should start HAART when their CD4 count fell below 200 cells/mm3 and should have their CD4 count regularly monitored to optimize HAART. In 2013, the World Health Organization (WHO) recommendations were updated to promote expanded eligibility for HAART with a CD4 of 500 cells/mm3 or less for adults, adolescents, and older children although priority is given to individuals with CD4 count of 350 cells/mm3 or less. Because HIV often becomes resistant to first-line antiretroviral drugs, WHO also recommends that viral load—the amount of virus in the blood—should be monitored so that suspected treatment failures can be confirmed and patients switched to second-line drugs in a timely manner. This monitoring and switching strategy is widely used in resource-rich settings, but is still very difficult to implement for low- and middle-income countries where resources for monitoring are limited and access to costly second-line drugs is restricted. In this randomized non-inferiority trial, the researchers compare the performance of a CD4-based treatment monitoring and switching strategy with the standard viral load-based strategy among HIV-positive adults in Thailand. In a randomized trial, individuals are assigned different interventions by the play of chance and followed up to compare the effects of these interventions; a non-inferiority trial investigates whether one treatment is not worse than another.
What Did the Researchers Do and Find?
The researchers assigned about 700 HIV-positive adults who were beginning HAART for the first time to have their CD4 count (CD4 arm) or their CD4 count and viral load (VL arm) determined every 3 months. Participants were switched to a second-line therapy if their CD4 count declined by more than 30% from their peak CD4 count (CD4 arm) or if a viral load of more than 400 copies/ml was recorded (VL arm). The 3-year cumulative risk of clinical failure (defined as death, a new AIDS-defining event, or a CD4 count of less than 50 cells/mm3) was 8% in the VL arm and 7.4% in the CD4 arm. This difference in clinical failure risk met the researchers' predefined criterion for non-inferiority. The probability of a treatment switch was similar in the two arms, but the average time from treatment initiation to treatment switch and the average duration of a high viral load after treatment switch were both longer in the CD4 arm than in the VL arm. Finally, the future-drug-option score, a measure of viral drug resistance profiles, was similar in the two arms at the time of treatment switch.
What Do These Findings Mean?
These findings suggest that, in Thailand, a CD4 switching strategy is non-inferior in terms of clinical outcomes among HIV-positive adults 3 years after beginning HAART when compared to the recommended viral load-based switching strategy and that there is no difference between the strategies in terms of viral suppression and immune restoration after 3-years follow-up. Importantly, however, even though patients in the CD4 arm spent longer with a high viral load than patients in the VL arm, the emergence of HIV mutants resistant to antiretroviral drugs was similar in the two arms. Although these findings provide no information about the long-term outcomes of the two monitoring strategies and may not be generalizable to routine care settings, they nevertheless provide reassurance that using CD4 counts alone to monitor HAART in HIV treatment programs in resource-limited settings is an appropriate strategy to use as viral load measurement becomes more affordable and feasible in these settings.
Additional Information
Please access these websites via the online version of this summary at
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2010 recommendations for antiretroviral therapy for HIV infection in adults and adolescents are available as well as the June 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV and AIDS in Thailand, on universal access to AIDS treatment, and on starting, monitoring and switching HIV treatment (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
More information about this trial (the PHPT-3 trial) is available
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about HIV treatment
PMCID: PMC3735458  PMID: 23940461
19.  Association of Single Nucleotide Polymorphisms in the Lens Epithelium-Derived Growth Factor (LEDGF/p75) with HIV-1 Infection Outcomes in Brazilian HIV-1+ Individuals 
PLoS ONE  2014;9(7):e101780.
The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1 gene, is an important host co-factor that interacts with HIV-1 integrase to target integration of viral cDNA into active genes. The aim of this study was to investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV-1 infected patients. We performed a genetic association study in a cohort of 171 HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n = 69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n = 23). The exonic SNP rs61744944 and 9 tag SNPs were genotyped. A group of 192 healthy subjects was analyzed to determine the frequency of SNPs and haplotypes in the general population. Linkage disequilibrium (LD) analyses indicated that the SNPs analyzed were not in high LD (r2<0.8). Logistic regression models suggested that patients carrying the T allele rs61744944 (472L) were more likely to develop a LTNP phenotype (OR = 4.98; p = 0.05) as compared to TP group. The same trend was observed when LTNPs were compared to the RP group (OR = 3.26). Results of haplotype analyses reinforced this association, since the OR values obtained for the haplotype carrying allele T at rs61744944 also reflected an association with LTNP status (OR = 6.05; p = 0.08 and OR = 3.44; p = 0.12 for comparisons to TP and RP, respectively). The rare missense variations Ile436Ser and Thr473Ile were not identified in the patients enrolled in this study. Gene expression analyses showed lower LEDGF/p75 mRNA levels in peripheral blood mononuclear cells obtained from HIV-1 infected individuals. However, these levels were not influenced by any of the SNPs investigated. In spite of the limited number of LTNPs, these data suggest that the PSIP1 gene could be associated with the outcome of HIV-1 infection. Further analyses of this gene may guide the identification of causative variants to help predict disease course.
PMCID: PMC4105638  PMID: 25047784
20.  A Randomized Controlled Trial Comparing the Effects of Counseling and Alarm Device on HAART Adherence and Virologic Outcomes 
PLoS Medicine  2011;8(3):e1000422.
Michael Chung and colleagues show that intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure, whereas use of an alarm device had no effect.
Behavioral interventions that promote adherence to antiretroviral medications may decrease HIV treatment failure. Antiretroviral treatment programs in sub-Saharan Africa confront increasing financial constraints to provide comprehensive HIV care, which include adherence interventions. This study compared the impact of counseling and use of an alarm device on adherence and biological outcomes in a resource-limited setting.
Methods and Findings
A randomized controlled, factorial designed trial was conducted in Nairobi, Kenya. Antiretroviral-naïve individuals initiating free highly active antiretroviral therapy (HAART) in the form of fixed-dose combination pills (d4T, 3TC, and nevirapine) were randomized to one of four arms: counseling (three counseling sessions around HAART initiation), alarm (pocket electronic pill reminder carried for 6 months), counseling plus alarm, and neither counseling nor alarm. Participants were followed for 18 months after HAART initiation. Primary study endpoints included plasma HIV-1 RNA and CD4 count every 6 months, mortality, and adherence measured by monthly pill count. Between May 2006 and September 2008, 400 individuals were enrolled, 362 initiated HAART, and 310 completed follow-up. Participants who received counseling were 29% less likely to have monthly adherence <80% (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.49–1.01; p = 0.055) and 59% less likely to experience viral failure (HIV-1 RNA ≥5,000 copies/ml) (HR 0.41; 95% CI 0.21–0.81; p = 0.01) compared to those who received no counseling. There was no significant impact of using an alarm on poor adherence (HR 0.93; 95% CI 0.65–1.32; p = 0.7) or viral failure (HR 0.99; 95% CI 0.53–1.84; p = 1.0) compared to those who did not use an alarm. Neither counseling nor alarm was significantly associated with mortality or rate of immune reconstitution.
Intensive early adherence counseling at HAART initiation resulted in sustained, significant impact on adherence and virologic treatment failure during 18-month follow-up, while use of an alarm device had no effect. As antiretroviral treatment clinics expand to meet an increasing demand for HIV care in sub-Saharan Africa, adherence counseling should be implemented to decrease the development of treatment failure and spread of resistant HIV.
Trial registration
ClinicalTrials gov NCT00273780
Please see later in the article for the Editors' Summary
Editors' Summary
Adherence to HIV treatment programs in poor countries has long been cited as an important public health concern, especially as poor adherence can lead to drug resistance and inadequate treatment of HIV. However, two factors have recently cast doubt on the poor adherence problem: (1) recent studies have shown that adherence is high in African HIV treatment programs and often better than in Western HIV clinics. For example, in a meta-analysis of 27 cohorts from 12 African countries, adequate adherence was noted in 77% of subjects compared to only 55% among 31 North America cohorts; (2) choice of antiretroviral regimens may impact on the development of antiretroviral resistance. In poor countries, most antiretroviral regimens contain non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as nevirapine or efavirenz, which remain in the patient's circulation for weeks after single-dose administration. This situation means that such patients may not experience antiretroviral resistance unless they drop below 80% adherence—contrary to the more stringent 95% plus adherence levels needed to prevent resistance in regimens based on unboosted protease inhibitors—ultimately, off-setting some treatment lapses in resource-limited settings where NNRTI-based regimens are widely used.
Why Was This Study Done?
Given that adherence may not be as crucial an issue as previously thought, antiretroviral treatment programs in sub-Saharan Africa may be spending scarce resources to promote adherence to the detriment of some potentially more effective elements of HIV treatment and management programs. Although many treatment programs currently include adherence interventions, there is limited quality evidence that any of these methods improve long-term adherence to HIV treatment. Therefore, it is necessary to identify adherence interventions that are inexpensive and proven to be effective in resource-limited settings. As adherence counseling is already widely implemented in African HIV treatment programs and inexpensive alarm devices are thought to also improve compliance, the researchers compared the impact of adherence counseling and the use of an alarm device on adherence and biological outcomes in patients enrolled in HIV programs in rural Kenya.
What Did the Researchers Do and Find?
The researchers enrolled 400 eligible patients (newly diagnosed with HIV, never before taken antiretroviral therapy, aged over 18 years) to four arms: (1) adherence counseling alone; (2) alarm device alone; (3) both adherence counseling and alarm device together; and (4) a control group that received neither adherence counseling nor alarm device. The patients had blood taken to record baseline CD4 count and HIV-1 RNA and after starting HIV treatment, returned to the study clinic every month with their pill bottles for the study pharmacist to count and recorded the number of pills remaining in the bottle, and to receive another prescription. Patients were followed up for 18 months and had their CD4 count and HIV-1 RNA measured at 6, 12, and 18 months.
Patients receiving adherence counseling were 29% less likely to experience poor adherence compared to those who received no counseling. Furthermore, those receiving intensive early adherence counseling were 59% less likely to experience viral failure. However, there was no significant difference in mortality or significant differences in CD4 counts at 18 months follow-up between those who received counseling and those who did not. There were no significant differences in adherence, time to viral failure, mortality, or CD4 counts in patients who received alarm devices compared to those who did not.
What Do These Findings Mean?
The results of this study suggest that intensive adherence counseling around the time of HIV treatment initiation significantly reduces poor adherence and virologic treatment failure, while using an alarm device has no effect. Therefore, investment in careful counseling based on individual needs at the onset of HIV treatment initiation, appears to have sustained benefit, possibly through strengthening the relationship between the health care provider and patient through communication, education, and trust. Interactive adherence counseling supports the bond between the clinic and the patient and may result in fewer patients needing to switch to expensive second-line medications and, possibly, may help to decrease the spread of resistant HIV. These findings define an adherence counseling protocol that is effective and are highly relevant to other HIV clinics caring for large numbers of patients in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at
UNAIDS provides information about HIV treatment strategies
The American Public Health Association has information about adherence to HIV treatment regimens
The US Department of Health and Human Services has information for patients about adherence to HIV treatment
The World Health Organization provides information about HIV treatment pharmacovigilance
PMCID: PMC3046986  PMID: 21390262
21.  The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference 
Niculae, Cristian-Mihail | Manea, Eliza | Jipa, Raluca | Merisor, Simona | Moroti, Ruxandra | Benea, Serban | Hristea, Adriana | Neguț, Alina Cristina | Săndulescu, Oana | Streinu-Cercel, Anca | Mărculescu, Dana | Andrei, Magdalena Lorena | Ilie, Veronica | Popa, Marcela | Bleotu, Coralia | Chifiriuc, Carmen | Popa, Mircea Ioan | Streinu-Cercel, Adrian | Orfanu, Alina | Popescu, Cristina | Leuștean, Anca | Catană, Remulus | Negru, Anca | Badea, Alexandra | Orfanu, Radu | Tilișcan, Cătălin | Aramă, Victoria | Aramă, Ştefan Sorin | Vișan, Constanța-Angelica | Drăgănescu, Anca-Cristina | Bilașco, Anuța | Kouris, Camelia | Merișescu, Mădălina | Vasile, Magdalena | Slavu, Diana-Maria | Vintilă, Sabina | Osman, Endis | Oprea, Alina | Sandu, Sabina | Luminos, Monica | Orfanu, Alina | Aramă, Victoria | Aramă, Ştefan Sorin | Leuştean, Anca | Catană, Remulus | Negru, Anca | Popescu, Gabriel Adrian | Popescu, Cristina | Stanculete, Ramona Georgiana | Enoiu, Ana Vaduva | Marinescu, Adelina Raluca | Lazureanu, Voichita | Marinescu, Adelina-Raluca | Crișan, Alexandru | Lăzureanu, Voichița | Musta, Virgil | Nicolescu, Narcisa | Laza, Ruxandra | Negru, Anca-Ruxandra | Munteanu, Daniela-Ioana | Mihăilescu, Raluca | Catană, Remulus | Dorobăț, Olga | Rafila, Alexandru | Căpraru, Emilia | Niculescu, Marius | Marinescu, Rodica | Lupescu, Olivera | Predescu, Vlad | Streinu-Cercel, Adrian | Aramă, Victoria | Tălăpan, Daniela | Popescu, Ramona Ștefania | Bradu, Luminița | Florea, Dragoș | Streinu-Cercel, Adrian | Leca, Daniela Anicuta | Bunea, Elena | Teodor, Andra | Miftode, Egidia | Merișescu, Mădălina | Jugulete, Gheorghiță | Streinu-Cercel, Adrian | Florea, Dragoș | Luminos, Monica | Popescu, Ramona Ștefania | Dobrotă, Anamaria | Ilie, Adina | Preoțescu, Liliana Lucia | Hristea, Adriana | Jipa, Raluca | Irimescu, Nicoleta | Panait, Irina | Manea, Eliza | Merisor, Simona | Niculae, Cristian | Tălăpan, Daniela | Gavriliu, Liana Cătălina | Benea, Otilia Elisabeta | Benea, Șerban | Rafila, Alexandru | Dorobăț, Olga | Popoiu, Mona | Dragonu, Livia | Cupşa, Augustin | Diaconescu, Iulian | Niculescu, Irina | Giubelan, Lucian | Dumitrescu, Florentina | Stoian, Andreea Cristina | Guţă, Camelia | Puiu, Simona | Irina, Bunescu | Vallée, Marilyse | Huletsky, Ann | Boudreau, Dominique K. | Bérubé, Ève | Giroux, Richard | Longtin, Jean | Longtin, Yves | Bergeron, Michel G. | Roșculeț, Cleo Nicoleta | Toma, Dalila-Ana | Ciuca, Catrinel | Tălăpan, Daniela | Apostolescu, Cătălin | Rogoz, Andrei | Stangaciu, Andrei | Mitescu, Viorica | Vladoiu, Tudor | Iovănescu, Doina | Oana, Michaela | Costin, Simona | Neguț, Alina Cristina | Săndulescu, Oana | Streinu-Cercel, Anca | Moțoi, Maria Magdalena | Popa, Mircea Ioan | Streinu-Cercel, Adrian | Tălăpan, Daniela | Dorobăț, Olga Mihaela | Popoiu, Mona | Mihai, Alexandru | Iovănescu, Doina | Roşculeț, Cleo | Apostolescu, Cătălin | Popescu, Gabriel-Adrian | Abagiu, Adrian | Moroti-Constantinescu, Ruxandra | Hristea, Adriana | Aramă, Victoria | Benea, Otilia | Simoiu, Mădălina | Bacruban, Rodica | Streinu-Cercel, Adrian | Rafila, Alexandru | Dorobăț, Olga Mihaela | Tălăpan, Daniela | Mihai, Alexandru | Bădicuț, Ioana | Popoiu, Mona | Borcan, Alina | Rafila, Alexandru | Popescu, Gabriel Adrian | Hurmuzache, Mihnea | Enache, Georgiana | Ciocan, Alexandra | Bararu, Mircea | Popazu, Madalina | Iovănescu, Doina Viorica | Roșculeț, Cleo Nicoleta | Rogoz, Andrei | Apostolescu, Cătălin Gabriel | Mitescu, Viorica | Vladoiu, Tudor | Toma, Dalila | Ciuca, Catrinel | Iliescu, Laura | Minzala, Georgiana | Toma, Letitia | Baciu, Mihaela | Tanase, Alina | Orban, Carmen | Pantea, Victor | Placinta, Gheorghe | Cebotarescu, Valentin | Cojuhari, Lilia | Jimbei, Paulina | Popescu, Cristina | Leuștean, Anca | Dragomirescu, Cristina | Orfanu, Alina | Murariu, Cristina | Stratan, Laurențiu | Badea, Alexandra | Tilișcan, Cătălin | Munteanu, Daniela | Năstase, Raluca | Molagic, Violeta | Rădulescu, Mihaela | Catană, Remulus | Aramă, Victoria | Popescu, Cristina | Stratan, Laurențiu | Catană, Remulus | Leuștean, Anca | Dragomirescu, Cristina | Badea, Alexandra | Murariu, Cristina | Năstase, Raluca | Molagic, Violeta | Munteanu, Daniela | Tilișcan, Cătălin | Rădulescu, Mihaela | Orfanu, Alina | Diaconu, Ioan | Negru, Anca | Bodosca, Iulia | Niță, Violeta | Aramă, Victoria | Leuștean, Anca | Aramă, Victoria | Orfanu, Alina | Catană, Remulus | Stratan, Laurențiu | Dragomirescu, Cristina | Murariu, Cristina | Badea, Alexandra | Tilișcan, Cătălin | Munteanu, Daniela | Molagic, Violeta | Năstase, Raluca | Rădulescu, Mihaela | Popescu, Cristina | Popescu, Cristina | Dragomirescu, Cristina | Leuștean, Anca | Murariu, Cristina | Stratan, Laurențiu | Badea, Alexandra | Catană, Remulus | Orfanu, Alina | Năstase, Raluca Mihaela | Molagic, Violeta | Munteanu, Daniela | Tilișcan, Cătălin | Aramă, Victoria | Aramă, Victoria | Catană, Remulus | Dragomirescu, Cristina | Murariu, Cristina | Leuștean, Anca | Stratan, Laurențiu | Badea, Alexandra | Orfanu, Alina | Negru, Anca | Năstase, Raluca | Molagic, Violeta | Munteanu, Daniela | Tilișcan, Cătălin | Rădulescu, Mihaela | Diaconu, Ioan | Niță, Violeta | Bodoșca, Iulia | Popescu, Cristina | Popescu, Cristina | Badea, Alexandra | Leuștean, Anca | Orfanu, Alina | Negru, Anca | Stratan, Laurențiu | Dragomirescu, Cristina | Catană, Remulus | Murariu, Cristina | Molagic, Violeta | Năstase, Raluca | Tilișcan, Cătălin | Munteanu, Daniela | Rădulescu, Mihaela | Diaconu, Ioan | Niță, Violeta | Bodoșca, Iulia | Aramă, Victoria | Popescu, Cristina | Orfanu, Alina | Leuștean, Anca | Badea, Alexandra | Stratan, Laurențiu | Catană, Remulus | Tilișcan, Cătălin | Aramă, Victoria | Popescu, Cristina | Murariu, Cristina | Dragomirescu, Cristina | Leuștean, Anca | Stratan, Laurențiu | Orfanu, Alina | Badea, Alexandra | Catană, Remulus | Negru, Anca | Tilișcan, Cătălin | Munteanu, Daniela | Rădulescu, Mihaela | Molagic, Violeta | Năstase, Raluca Mihaela | Diaconu, Ioan Alexandru | Bodoșca, Iulia | Niță, Violeta | Aramă, Victoria | Erturk, Yagmur | Săndulescu, Oana | Neguț, Alina Cristina | Șchiopu, Claudiu Mihai | Streinu-Cercel, Adrian | Streinu-Cercel, Anca | Molagic, Violeta | Tilișcan, Cătălin | Popescu, Cristina | Mihăilescu, Raluca | Munteanu, Daniela | Năstase, Raluca | Negru, Anca | Tenita, Angelica | Aramă, Victoria | Aramă, Ștefan Sorin | Iacob, Simona Alexandra | Iacob, Diana Gabriela | Luminos, Monica | Streinu-Cercel, Anca | Săndulescu, Oana | Predescu, Mioara | Mărdărescu, Alexandra | Tilișcan, Cătălin | Săndulescu, Mihai | Șchiopu, Claudiu Mihai | Streinu-Cercel, Adrian | Roșculeț, Cleo Nicoleta | Ciuca, Catrinel Olimpia | Toma, Dalila Ana | Apostolescu, Cătălin Gabriel | Rogoz, Andrei | Mitu, Cristina Elena | Stangaciu, Andrei | Mitescu, Viorica Daniela | Vladoiu, Tudor Gheorghe | Iovănescu, Doina Viorica | Săndulescu, Oana | Streinu-Cercel, Anca | Stoica, Monica Andreea | Preoțescu, Liliana Lucia | Manolache, Daniela | Ceapraga, Gabriela Jana | Moțoi, Maria Magdalena | Bradu, Luminița | Ilie, Adina | Mircea, Gabriela | Durbală, Ionel | Streinu-Cercel, Adrian | Russu, Irina | Holban, Tiberiu | Pantilimonov, Tatiana | Chiriacov, Galina | Macvovei, Arcadie | Scorohodico, Elena | Dmitriev, Oleg | Costache, Diana Alexandra | Benea, Anca | Manea, Eliza | Niculae, Cristian | Jipa, Raluca | Hristea, Adriana | Benea, Elisabeta | Moroti, Ruxandra | Benea, Șerban | Mitran, Mihai | Georgescu, Carmen | Mitran, Loredana | Vladareanu, Simona | Magirescu, Andreea Ioana | Andreev, Viorica | Nicolau, Cristina | Largu, Alexandra | Dorobat, Carmen | Manciuc, Carmen | Andreev, Viorica | Magirescu, Andreea Ioana | Isac, Ina | Nicolau, Cristina | Largu, Alexandra | Dorobat, Carmen | Manciuc, Carmen | Șerban, Iulia Gabriela | Resul, Ghiulendan | Marcaș, Consuela | Marincu, Iosif | Poptelecan, Patricia | Trincă, Bogdan | Mitrescu, Sorina | Tudor, Anca | Vlad, Daliborca | Tirnea, Livius | Baydaroglu, Nurcan | Neguț, Alina Cristina | Săndulescu, Oana | Manolache, Daniela | Ceapraga, Gabriela | Stoica, Monica Andreea | Streinu-Cercel, Anca | Streinu-Cercel, Adrian | Manciuc, Carmen | Pagute, Mariana | Nicolau, Cristina | Dorobăț, Carmen | Largu, Alexandra | Diaconu, Ioan-Alexandru | Stratan, Laurențiu | Ion, Daniela | Nichita, Luciana | Popescu, Cristina | Năstase, Raluca | Munteanu, Daniela | Molagic, Violeta | Tilișcan, Cătălin | Rădulescu, Mihaela | Diaconu, Alexandra | Negru, Anca | Orfanu, Alina | Dragomirescu, Cristina | Catană, Remulus | Leuștean, Anca | Duport-Dodot, Irina | Murariu, Cristina | Bodoșca, Iulia | Niță, Violeta | Badea, Alexandra | Aramă, Victoria | Mărdărescu, Mariana | Petre, Cristina | Iancu, Marieta | Ungurianu, Rodica | Cibea, Alina | Drăghicenoiu, Ruxandra | Tudor, Ana Maria | Vlad, Delia | Petrea, Sorin | Matei, Carina | Oțelea, Dan | Crăciun, Carmen | Anghelina, Cristian | Mărdărescu, Alexandra | Dumea, Elena | Streinu-Cercel, Adrian | Rugină, Sorin | Petcu, Lucian Cristian | Halichidis, Stela | Cambrea, Simona Claudia | Chiriac, Carmen | Bodnar, Nina-Ioana | Zaharia-Kezdi, Iringo-Erzsebet | Gîrbovan, Cristina | Incze, Andrea | Georgescu, Anca Meda | Iacob, Simona Alexandra | Iacob, Diana Gabriela | Panaitescu, Eugenia | Luminos, Monica | Cojocaru, Manole | Iacob, Simona Alexandra | Iacob, Diana Gabriela | Luminos, Monica | Laurențiu, Vochita | Andreia, Vochita | Radu, Opreanu | Bogdan, Trinca | Ovidiu, Rosca | Iosif, Marincu | Zamfir, Ramona | Angelescu, Alina | Popa, Alena Andreea | Jipa, Raluca | Moroti, Ruxandra | Hristea, Adriana | Gavriliu, Liana | Benea, Șerban | Benea, Elisabeta | Popa, Alena-Andreea | Ducu, Georgeta | Camburu, Daniela | Cozma, Alina | Podani, Manuela | Dumitriu, Roxana | Gavriliu, Liana | Benea, Șerban | Benea, Elisabeta | Stoian, Andreea Cristina | Dumitrescu, Florentina | Cupșa, Augustin | Giubelan, Lucian | Niculescu, Irina | Ionescu, Loredana | Dragonu, Livia | Abagiu, Adrian Octavian | Stoica, Loredana Nicoleta | Blaga, Catrinel | Koulosousas, Archontis | Ștefănescu, Roxana | Atomoaie, Alice | Paraschiv, Florentina | Duna, Florin Matache | Olteanu, Rodica | Ion, Roxana | Zota, Alexandra | Jaballah, Isra Ennour | Mahfoud, Lara | Preda, Georgeta | Constantin, Magda | Nicolae, Ilinca | Ene, Corina Daniela | Mitran, Mădălina Irina | Benea, Vasile | Tampa, Mircea | Georgescu, Simona Roxana | Bodoșca, Iulia Cristina | Murariu, Cristina | Tilișcan, Cătălin | Aramă, Victoria | Popescu, Cristina | Munteanu, Daniela | Rădulescu, Mihaela | Molagic, Violeta | Năstase, Raluca | Orfanu, Alina | Leuștean, Anca | Catană, Remulus | Negru, Anca | Streinu-Cercel, Adrian | Aramă, Sorin | Caramăngiu, Iuliana | Rosca, Ovidiu | Cialma, Monica | Opreanu, Radu | Vochita, Laurențiu | Marincu, Iosif | Murărescu, Vlad | Palaghiță, Marilena | Neguț, Alina Cristina | Camburu, Cornel | Streinu-Cercel, Adrian | Duşan, Irina | Poptelecan, Patricia | Trincă, Bogdan | Mitrescu, Sorina | Tirnea, Livius | Marincu, Iosif | Nicolescu, Narcisa | Crișan, Alexandru | Lăzureanu, Voichița | Laza, Ruxandra | Musta, Virgil | Marinescu, Adelina-Raluca | Bîrlad, Andreea | Miron, Victor Daniel | Drăgănescu, Anca Cristina | Vișan, Constanța-Angelica | Bilașco, Anuța | Pițigoi, Daniela | Săndulescu, Oana | Luminos, Monica Luminița | Luminos, Monica | Osman, Endis | Vasile, Magdalena | Drăgănescu, Anca Cristina | Vișan, Constanța-Angelica | Bilașco, Anuța | Kouris, Camelia | Șchiopu, Sabina | Merișescu, Mădălina | Luminos, Monica | Drăgănescu, Anca Cristina | Vișan, Constanța-Angelica | Bilașco, Anuța | Kouris, Camelia | Osman, Endis | Vintilă, Sabina | Vasile, Magda | Merișescu, Mădălina | Gavriliu, Liana Cătălina | Benea, Otilia Elisabeta | Angelescu, Alina | Zamfir, Ramona | Camburu, Daniela | Ducu, Georgeta | Cozma, Alina | Dumitriu, Roxana | Podani, Manuela | Benea, Șerban | Ionică, Mihaela | Jugulete, Gheorghiță | Stăncescu, Adina | Popescu, Cristina Elena | Marin, Luminița | Zaharia, Diana | Dumitrescu, Cristina | Tudor, Lucia | Vintilă, Sabina | Vișan, Constanța-Angelica | Drăgănescu, Anca Cristina | Bilașco, Anuța | Vasile, Magda | Merișescu, Mădălina | Kouris, Camelia | Negulescu, Cristina | Osman, Endis | Slavu, Diana-Maria | Vintilă, Sabina | Pițigoi, Daniela | Luminos, Monica | Caliman-Sturdza, Olga Adriana | Roșculeț, Cleo | Ciuca, Catrinel Olimpia | Toma, Dalila | Apostolescu, Cătălin | Rogoz, Andrei | Stangaciu, Andrei | Mitescu, Viorica | Iovănescu, Doina | Camburu, Cornel | Manu, Bogdana | Vaduva-Enoiu, Ana | Stanculete, Ramona Georgiana | Marinescu, Adelina Raluca | Lazureanu, Voichita Elena | Niță, Elena-Violeta | Dumitru, Sînziana | Munteanu, Daniela-Ioana | Negru, Anca Ruxandra | Catană, Remulus | Diaconu, Ioan | Manu, Bogdana | Ionescu, Ligia | Ion, Liliana | Tilișcan, Cătălin | Aramă, Victoria | Iovănescu, Doina Viorica | Roșculeț, Cleo Nicoleta | Rogoz, Andrei | Apostolescu, Cătălin | Mitescu, Viorica | Vladoiu, Tudor | Toma, Dalila | Ciuca, Catrinel | Șerban, Iulia Gabriela | Neacșu, Marioara | Georgescu, Simona Roxana | Benea, Vasile | Ene, Corina Daniela | Tampa, Mircea | Mitran, Cristina Iulia | Nicolae, Ilinca | Pribac, George Ciprian | Prisca, Mirandolina | Ursoiu, Fulvia | Neamtu, Carmen | Totolici, Bogdan | Cotoraci, Coralia | Ardelean, Aurel | Albu, Simona Elena | Carsote, Mara | Miclăuș, Beatrice | Mihai, Diana | Săndulescu, Oana | Vasiliu, Cristina | Vasiliu, Cristina | Carsote, Mara | Gorgoi, Corina | Miclăuș, Beatrice | Mihai, Diana | Săndulescu, Oana | Albu, Simona Elena | Blescun, Amelia | Breaza, Gelu | Vintila, Sabina | Mihai, Felicia | Omer, Meilin | Dragan, Cornel | Pitigoi, Daniela | Ciucu, Mirela | Ionescu, Marius-Dan | Roskanovic, Cristina | Barbu, Valentina | Diaconescu, Iulian | Dumitrescu, Florentina | Niculescu, Irina | Ionică, Mihaela | Zamfir, Ramona-Alexandra | Cozma, Alina | Benea, Otilia Elisabeta | Dumitru, Alexandra-Sînziana | Munteanu, Daniela-Ioana | Niță, Violeta | Popescu, Cristina | Bodosca, Iulia | Tenita, Angelica | Ispas, Viorica | Aramă, Victoria | Benea, Vasile | Georgescu, Simona Roxana | Tampa, Mircea | Leahu, Diana Oana | Safta, Cristina Maria | Benea, Mihaela Anca | Săndulescu, Oana | Munteanu, Octavian | Bohâlțea, Roxana | Trașcă, Livia | Cîrstoiu, Monica | Iovănescu, Doina Viorica | Roșculeț, Cleo Nicoleta | Rogoz, Andrei | Apostolescu, Cătălin Gabriel | Mitescu, Viorica Daniela | Vladoiu, Tudor Gheorghe | Toma, Dalila | Ciuca, Catrinel | Georgescu, Mădălina | Pițigoi, Daniela | Ivanciuc, Alina Elena | Lazar, Mihaela | Ionescu, Teodora | Cherciu, Carmen Maria | Țecu, Cristina | Mihai, Maria Elena | Nițescu, Maria | Bacruban, Rodica | Azamfire, Delia | Dumitrescu, Aura | Ianosik, Elena | Leca, Daniela | Duca, Elena | Teodor, Andra | Bejan, Codrina | Ceaușu, Emanoil | Florescu, Simin-Aysel | Popescu, Corneliu | Târdei, Grațiela | Juganariu, Codrina | Lupulescu, Emilia | Rodina, Ligia | Cocuz, Maria Elena | Jugulete, Gheorghiță | Stăncescu, Adina | Popescu, Cristina Elena | Marin, Luminița | Zaharia, Diana | Dumitrescu, Cristina | Osman, Endis | Niculescu, Irina | Cupșa, Augustin | Diaconescu, Iulian | Dumitrescu, Florentina | Dragonu, Livia | Stoian, Andreea | Giubelan, Lucian | Roskanovic, Cristina | Zamfir, Ramona-Alexandra | Ionica, Mihaela | Benea, Otilia-Elisabeta | Sîrbu, Maria-Cristina | Dobrotă, AnaMaria | Neguț, Alina Cristina | Duda, Roxana | Bacruban, Rodica | Pițigoi, Daniela | Dragomirescu, Cristiana Cerasella | Tălăpan, Daniela | Dorobăț, Olga | Streinu-Cercel, Adrian | Streinu-Cercel, Anca | Ionica, Mihaela | Zamfir, Ramona-Alexandra | Cozma, Alina | Benea, Otilia Elisabeta | Fendrihan, Sergiu | Scortan, Ecaterina | Popa, Mircea Ioan | Popescu, Corneliu P. | Benea, Șerban N. | Petcu, Andra E. | Hristea, Adriana | Abagiu, Adrian | Podea, Iuliana A. | Jipa, Raluca E. | Ducu, Georgeta | Hrișcă, Raluca M. | Florea, Dragoș | Nica, Manuela | Manea, Eliza | Merișor, Simona | Nicolae, Cristian M. | Florescu, Simin A. | Dumitru, Irina M. | Ceaușu, Emanoil | Rugină, Sorin | Moroti, Ruxandra V. | Pițigoi, Daniela | Ionescu, Teodora | Săndulescu, Oana | Nițescu, Maria | Nițescu, Bogdan | Mustaţă, Iulia Monica | Boldeanu, Sorina Claudia | Furtunescu, Florentina | Streinu-Cercel, Adrian | Iacob, Diana Gabriela | Iacob, Simona Alexandra | Gheorghe, Mihaela | Slavcovici, Adriana | Tripon, Raluca | Iubu, Roxana | Marcu, Cristian | Sabou, Mihaela | Muntean, Monica | Chiriac, Ion | Holban, Tiberiu | Tazlavanu, Liviu | Jipa, Raluca | Manea, Eliza | Cernat, Roxana | Iringo, Kezdi | Vâță, Andrei | Arbune, Manuela | Moisil, Teodora | Hristea, Adriana | Ene, Corina-Daniela | Nicolae, Ilinca | Georgescu, Roxana Simona | Ene, Corina-Daniela | Ene, Cosmin-Victor | Georgescu, Roxana Simona | Ciortea, Marilena | Dulgheru, Lucreția | Nicolae, Ilinca | Luca, Mihaela Cătălina | Harja-Alexa, Ioana-Alina | Nemescu, Roxana | Popazu, Mădălina | Luca, Andrei Ștefan | Bancescu, Gabriela | Dabu, Bogdan | Bancescu, Adrian | Manea, Eliza | Jipa, Raluca | Hristea, Adriana | Ilie, Adina Elena | Pohrib, Săftica-Mariana | Neguț, Alina Cristina | Tache, Maria-Sabina | Moțoi, Maria Magdalena | Săndulescu, Oana | Iliescu, Ion Aurel | Streinu-Cercel, Adrian | Tecu, Cristina | Mihai, Maria-Elena | Lazăr, Mihaela | Cherciu, Carmen | Ivanciuc, Alina | Pițigoi, Daniela | Lupulescu, Emilia | Paliu, Mirela | Curescu, Manuela | Cerbu, Bianca | Marincu, Iosif | Mihai, Maria Elena | Cherciu, Carmen Maria | Ivanciuc, Alina Elena | Tecu, Cristina | Lupulescu, Emilia | Bunescu, Irina | Holban, Tiberiu | Pasnin, Ana | Semeniuc, Stela | Popovici, Raisa | Chiriacov, Galina
BMC Infectious Diseases  2016;16(Suppl 4):31-76.
Table of contents
A1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in Bucharest
Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea
A2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteria
Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel
A3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and future
Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă
A4 Etiologic and clinical features of bacterial meningitis in infants
Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos
A5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsis
Alina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina Popescu
A6 Whooping cough in a HIV positive patient
Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu
A7 Cronobacter sakazakii sepsis in varicella patient
Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza
A8 Anaerobes an underdiagnosed cause of prosthesis joint infection
Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela Tălăpan
A9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentation
Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-Cercel
A10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 cases
Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode
A11 The molecular diagnosis of severe bacterial sepsis in pediatric population
Mădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica Luminos
A12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentation
Ramona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu
A13 Is Streptococcus suis meningitis an under-diagnosed zoonosis?
Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela Tălăpan
A14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and present
Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona Popoiu
A15 Antibiotics resistance in Staphylococcus aureus isolated from blood cultures
Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu
A16 Predominance of CTX-M enzymes in extended-spectrum β-lactamase-producing Enterobacteriaceae in two hospitals of Quebec City
Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron
A17 Postoperative meningoencephalitis with Acinetobacter baumannii XDR – a therapeutic challenge - Case report
Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Daniela Tălăpan, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu
A18 Septic arthritis with Burkholderia cepacia
Michaela Oana, Simona Costin
A19 A novel approach for managing hard-to-treat infections
Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Maria Magdalena Moțoi, Mircea Ioan Popa, Adrian Streinu-Cercel
A20 Nineteen months surveillance for multidrug resistant organisms (MDRO) by detecting asymptomatic colonization
Daniela Tălăpan, Olga Mihaela Dorobăț, Mona Popoiu, Alexandru Mihai, Doina Iovănescu, Cleo Roşculeț, Cătălin Apostolescu, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Adriana Hristea, Victoria Aramă, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Adrian Streinu-Cercel, Alexandru Rafila
A21 Antimicrobial resistance of Gram-positive cocci isolated from clinical specimens in the National Institute of Infectious Diseases “Prof Dr. Matei Balș” between 2009–2015
Olga Mihaela Dorobăț, Daniela Tălăpan, Alexandru Mihai, Ioana Bădicuț, Mona Popoiu, Alina Borcan, Alexandru Rafila
A22 The high percentage of carbapenem-resistant Gram-negative bacilli in Romania: an analysis and some proposals
Gabriel Adrian Popescu
A23 Etiological, clinical and therapeutic considerations on 78 cases of healthcare associated meningitis or ventriculitis admitted in the “Sf. Parascheva” infectious diseases clinical hospital, Iași, from 2011 to 2015
Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu
A24 Nosocomial infection dynamics in an Intensive Care Department – an overview (epidemiological and clinical monitoring, advanced therapeutic intervention).
Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz Cătălin Gabriel Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca
A25 Safety and efficacy of interferon free treatment in patients with HCV chronic hepatitis- experience of a single Internal Medicine center
Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban
A26 Viusid in treatment of chronic viral hepatitis B and C
Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei
A27 The management of hyperbilirubinemia in HCV cirrhotic patients who underwent therapy with direct acting antivirals
Cristina Popescu, Anca Leuștean, Cristina Dragomirescu, Alina Orfanu, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Remulus Catana, Victoria Aramă
A28 The efficacy of ombitasvir-paritaprevir/ritonavir, dasabuvir and ribavirin in patients with genotype 1 HCV compensated cirrhosis
Cristina Popescu, Laurențiu Stratan, Remulus Catana, Anca Leuștean, Cristina Dragomirescu, Alexandra Badea, Cristina Murariu, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Alina Orfanu, Ioan Diaconu, Anca Negru, Iulia Bodosca, Violeta Niță, Victoria Aramă
A29 The efficacy of direct acting antivirals regimen without ribavirin in HCV genotype 1b infected patients with compensated cirrhosis
Anca Leuștean, Victoria Aramă, Alina Orfanu, Remulus Catana, Laurențiu Stratan, Cristina Dragomirescu, Cristina Murariu, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Violeta Molagic, Raluca Năstase, Mihaela Rădulescu, Cristina Popescu
A30 Liver decompensation during ombitasvir-paritaprevir/ritonavir-dasabuvir and ribavirin regimen in HCV infected patients with Child-Pugh A cirrhosis
Cristina Popescu, Cristina Dragomirescu, Anca Leuștean, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Remulus Catană, Alina Orfanu, Raluca Mihaela Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Victoria Aramă
A31 The safety of direct acting antivirals in HCV compensated cirrhotic patients - an interim analysis
Victoria Aramă, Remulus Catană, Cristina Dragomirescu, Cristina Murariu, Anca Leuștean, Laurențiu Stratan, Alexandra Badea, Alina Orfanu, Anca Negru, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Cristina Popescu
A32 The access of patients with HCV compensated cirrhosis to the National Program of therapy with direct acting antivirals
Cristina Popescu, Alexandra Badea, Anca Leuștean, Alina Orfanu, Anca Negru, Laurențiu Stratan, Cristina Dragomirescu, Remulus Catană, Cristina Murariu, Violeta Molagic, Raluca Năstase, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Victoria Aramă
A33 Severe reactivation of chronic hepatitis B after discontinuation of nucleos(t)ide analogues – a case series
Cristina Popescu, Alina Orfanu, Anca Leuștean, Alexandra Badea, Laurențiu Stratan, Remulus Catană, Cătălin Tilișcan, Victoria Aramă
A34 The dynamic of hematological disorders during direct acting antivirals therapy for HCV compensated cirrhosis
Cristina Popescu, Cristina Murariu, Cristina Dragomirescu, Anca Leuștean, Laurențiu Stratan, Alina Orfanu, Alexandra Badea, Remulus Catană, Anca Negru, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Mihaela Năstase, Ioan Alexandru Diaconu, Iulia Bodoșca, Violeta Niță, Victoria Aramă
A35 Behaviors, attitudes and risk factors for viral hepatitis in international medical students vs. the general population in Romania
Yagmur Erturk, Oana Săndulescu, Alina Cristina Neguț, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel, Anca Streinu-Cercel
A36 Characteristics of hepatitis C virus reactivation due to immunosuppressive therapy in Romanian HCV infected patients with hematological malignancies
Violeta Molagic, Cătălin Tilișcan, Cristina Popescu, Raluca Mihăilescu, Daniela Munteanu, Raluca Năstase, Anca Negru, Angelica Tenita, Victoria Aramă, Ștefan Sorin Aramă
A37 The dynamic IFN-gamma serum levels during successful peginterferon-a 2a/ribavirin therapy in HCV chronic infection
Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos
A38 Overlapping risk factors for transmission of HBV, HCV and HIV in the general population in Romania
Anca Streinu-Cercel, Oana Săndulescu, Mioara Predescu, Alexandra Mărdărescu, Cătălin Tilișcan, Mihai Săndulescu, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel
A39 Acute hepatitis - an uncommon neurological complication
Cleo Nicoleta Roșculeț, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cătălin Gabriel Apostolescu, Andrei Rogoz, Cristina Elena Mitu, Andrei Stangaciu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Doina Viorica Iovănescu
A40 Regression of liver fibrosis following sustained virological response in patients with chronic HCV infection and cirrhosis
Oana Săndulescu, Anca Streinu-Cercel, Monica Andreea Stoica, Liliana Lucia Preoțescu, Daniela Manolache, Gabriela Jana Ceapraga, Maria Magdalena Moțoi, Luminița Bradu, Adina Ilie, Gabriela Mircea, Ionel Durbală, Adrian Streinu-Cercel
A41 Preliminary results of treatment with sofosbuvir and daclatasvir of patients with chronic hepatitis C
Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev
A42 HIV-syphilis coinfection
Diana Alexandra Costache, Anca Benea, Eliza Manea, Cristian Niculae, Raluca Jipa, Adriana Hristea, Elisabeta Benea, Ruxandra Moroti, Șerban Benea
A43 Thrombophilia – additional risk factor for the evolution of pregnancy in HIV-positive patients
Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu
A44 The incidence of oropharyngeal candidiasis in hospitalized HIV infected pediatric Romanian cohort between 1 January - 31 December 2015
Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc
A45 TB incidence in HIV infected patients during the year of 2015
Viorica Andreev, Andreea Ioana Magirescu, Ina Isac, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc
A46 Retrospective analysis of HIV/AIDS deaths recorded in the Clinical Infectious Diseases Hospital, Constanța in the period 01 January 2014–30 June 2016. Epidemiological considerations.
Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș
A47 Acute liver failure with favorable evolution in an HIV-HBV coinfected patient
Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea
A48 Lifestyle impact on HIV management
Nurcan Baydaroglu, Alina Cristina Neguț, Oana Săndulescu, Daniela Manolache, Gabriela Ceapraga, Monica Andreea Stoica, Anca Streinu-Cercel, Adrian Streinu-Cercel
49. HIV positive mothers newborns - clinical experience from January 2012 to June 2016
Carmen Manciuc, Mariana Pagute, Cristina Nicolau, Carmen Dorobăț, Alexandra Largu
A50 Rediscovering HIV-associated progressive multifocal leukoencephalopathy and HIV encephalopathy: clinical suspicion and subsequent brain autopsies
Ioan-Alexandru Diaconu, Laurențiu Stratan, Daniela Ion, Luciana Nichita, Cristina Popescu, Raluca Năstase, Daniela Munteanu, Violeta Molagic, Cătălin Tilișcan, Mihaela Rădulescu, Alexandra Diaconu, Anca Negru, Alina Orfanu, Cristina Dragomirescu, Remulus Catană, Anca Leuștean, Irina Duport-Dodot, Cristina Murariu, Iulia Bodoșca, Violeta Niță, Alexandra Badea, Victoria Aramă
A51 Antenatal surveillance of pregnant women with risk behavior and its impact on mother-to-child HIV transmission in Romania
Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Alexandra Mărdărescu
A52 Noninvasive assessments (APRI, Fib-4, transient elastography) of fibrosis in patients with HIV and HIV/HBV infection
Elena Dumea, Adrian Streinu-Cercel, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea
A53 Undetectable HIV viral load – the main goal in the management of HIV-infected patients
Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu
A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients
Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru
A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection
Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos
A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient
Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif
A57 Evolution of antiretroviral regimens in naϊve patients in 2016
Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea
A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015
Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea
A59 Epidemiological aspects of HIV infection in Oltenia region
Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu
A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT) from Arena center, Bucharest
Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna
A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters
Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin
A62 Prevalence of autoantibodies against gangliosides in asymptomatic HIV-infected patients
Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu
A63 Subclinical inflammation in HIV-infected patients undergoing antiretroviral therapy – a cross sectional study
Iulia Cristina Bodoșca, Cristina Murariu, Cătălin Tilișcan, Victoria Aramă, Cristina Popescu, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Năstase, Alina Orfanu, Anca Leuștean, Remulus Catană, Anca Negru, Adrian Streinu-Cercel, Sorin Aramă
A64 Severe Guillain-Barré syndrome occurring after chickenpox with favorable evolution
Iuliana CAramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Iosif Marincu
A65 Echovirus 30 infection with pulmonary and cardiac complications – case report
Vlad Murărescu, Marilena Palaghiță, Alina Cristina Neguț, Cornel Camburu, Adrian Streinu-Cercel
A66 Herpetic encephalitis with favorable evolution in an adult immunocompetent patient
Irina Duşan, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Livius Tirnea, Iosif Marincu
A67 Clinical-evolutional aspects in present-day measles
Narcisa Nicolescu, Alexandru Crișan, Voichița Lăzureanu, Ruxandra Laza, Virgil Musta, Adelina-Raluca Marinescu, Andreea Bîrlad
A68 Pneumococcal superinfection in children with influenza
Victor Daniel Miron, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Daniela Pițigoi, Oana Săndulescu, Monica Luminița Luminos
A69 Varicella complicated with transverse myelitis - case presentation
Monica Luminos, Endis Osman, Magdalena Vasile, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Sabina Șchiopu, Mădălina Merișescu
A70 Clinical forms of enterovirus infections during the summer season of 2016
Monica Luminos, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Endis Osman, Sabina Vintilă, Magda Vasile, Mădălina Merișescu
A71 Face off – HIV and lymphoma – case series presentation
Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Alina Angelescu, Ramona Zamfir, Daniela Camburu, Georgeta Ducu, Alina Cozma, Roxana Dumitriu, Manuela Podani, Șerban Benea, Mihaela Ionică
A72 Coxsackie infection complicated by pancytopenia – pediatric case report
Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Sabina Vintilă
A73 Viral respiratory infections in children in the season 2015–2016
Constanța-Angelica Vișan, Anca Cristina Drăgănescu, Anuța Bilașco, Magda Vasile, Mădălina Merișescu, Camelia Kouris, Cristina Negulescu, Endis Osman, Diana-Maria Slavu, Sabina Vintilă, Daniela Pițigoi, Monica Luminos
A75 The severity of A H1N1 Influenza infection in the 2015–2016 season
Cleo Roșculeț, Catrinel Olimpia Ciuca, Dalila Toma, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Doina Iovănescu, Cornel Camburu, Bogdana Manu
A76 Acute respiratory distress syndrome in a child with measles
Ana Vaduva-Enoiu, Ramona Georgiana Stanculete, Adelina Raluca Marinescu, Voichita Elena Lazureanu
A77 Management challenges of right-sided infectious endocarditis in an HIV positive patient – case presentation
Elena-Violeta Niță, Sînziana Dumitru, Daniela-Ioana Munteanu, Anca Ruxandra Negru, Remulus Catană, Ioan Diaconu, Bogdana Manu, Ligia Ionescu, Liliana Ion, Cătălin Tilișcan, Victoria Aramă
A78 Bacterial infection in critical patients with severe A H1N1 influenza virus infection (epidemiology, development, therapeutic decisions)
Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca
A79 Epidemiological aspects of severe acute respiratory infection cases (SARI) in the season 2015–2016, in the Clinical Hospital of Infectious Diseases – Constanța, Romania
Iulia Gabriela Șerban, Marioara Neacșu
A80Overexpression of IL-6 trans signaling pathway in viral infections
Simona Roxana Georgescu, Vasile Benea, Corina Daniela Ene, Mircea Tampa, Cristina Iulia Mitran, Ilinca Nicolae
A81 Acute viral hepatitis B with persistent HBsAg – description and evolution
George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean
A82 Prevalence of cervical pathogens in a population of pregnant female patients monitored in a tertiary care hospital in Bucharest, Romania
Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Cristina Vasiliu
A83 Prevalence of group B Streptococcus during pregnancy in a cohort of patients monitored in a tertiary care hospital in Bucharest, Romania
Cristina Vasiliu, Mara Carsote, Corina Gorgoi, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Simona Elena Albu
A84 Infectious hematoma in the gastrocnemius muscle – case presentation
Amelia Blescun, Gelu Breaza
A85 Reflections towards the underexplored HTLV Romanian viral circulation - adult T‐cell leukemia/lymphomas, a case series
Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi
A86 A febrile confusion syndrome with acute onset – case presentation
Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Iulian Diaconescu, Florentina Dumitrescu, Irina Niculescu
A87 Retrobulbar optic neuritis in a HIV-positive patient - case report
Mihaela Ionică, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea
A88 A rare presentation of Q fever – case presentation
Alexandra-Sînziana Dumitru, Daniela-Ioana Munteanu, Violeta Niță, Cristina Popescu, Iulia Bodosca, Angelica Tenita, Viorica Ispas, Victoria Aramă
A89 Tinea incognita – case presentation
Vasile Benea, Simona Roxana Georgescu, Mircea Tampa, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea
A90 Incidence and risk factors associated with TORCH infections during pregnancy
Oana Săndulescu, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu
A91 Acute respiratory failure in critical patients with sepsis
Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Gabriel Apostolescu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Dalila Toma, Catrinel Ciuca
A92 Cochleo-vestibular deficit secondary to Granulicatella elegans meningitis
Mădălina Georgescu
A93 Influenza 2015/2016 – clinical, epidemiological and virological characteristics of cases admitted in three infectious diseases hospitals
Daniela Pițigoi, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Rodica Bacruban, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Andra Teodor, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu
A94 Severe complications of varicella requiring hospitalization in previously healthy children in Brașov county
Ligia Rodina, Maria Elena Cocuz
A95 Clinical forms of Clostridium difficile colitis in children
Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Endis Osman
A96 Community-acquired pneumonia – demographic, clinical and etiological aspects
Irina Niculescu, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Livia Dragonu, Andreea Stoian, Lucian Giubelan, Cristina Roskanovic
A97 Acute myocarditis in an adult patient with chickenpox - Case report
Ramona-Alexandra Zamfir, Mihaela Ionica, Otilia-Elisabeta Benea
A98 Caustic oropharyngeal wound with acute group F streptococcal superinfection mimicking diphtheria – case report and differential diagnosis
Maria-Cristina Sîrbu, AnaMaria Dobrotă, Alina Cristina Neguț, Roxana Duda, Rodica Bacruban, Daniela Pițigoi, Cristiana Cerasella Dragomirescu, Daniela Tălăpan, Olga Dorobăț, Adrian Streinu-Cercel, Anca Streinu-Cercel
A99 Clostridium difficile infection in HIV-positive patients admitted in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015
Mihaela Ionica, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea
A100 Title: Epidemiology of Candida oral infections (stomatitis) in Romania
Sergiu Fendrihan, Ecaterina Scortan, Mircea Ioan Popa
A101 Anthrax case series in south-eastern Romania
Corneliu P Popescu, Șerban N Benea, Andra E Petcu, Adriana Hristea, Adrian Abagiu, Iuliana A Podea, Raluca E Jipa, Georgeta Ducu, Raluca M Hrișcă, Dragoș Florea, Manuela Nica, Eliza Manea, Simona Merișor, Cristian M Nicolae, Simin A Florescu, Irina M Dumitru, Emanoil Ceaușu, Sorin Rugină, Ruxandra V Moroti
A102 Knowledge, risk perception and attitudes of healthcare workers at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” regarding Ebola
Daniela Pițigoi, Teodora Ionescu, Oana Săndulescu, Maria Nițescu, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Adrian Streinu-Cercel
A103 A case of abdominopelvic actinomycosis with successful short-term antibiotic treatment
Diana Gabriela Iacob, Simona Alexandra Iacob, Mihaela Gheorghe
A104 A case of pneumonia caused by Raoultella planticola
Iulian Diaconescu, Irina Niculescu, Floretina Dumitrescu, Lucian Giubelan
A105 Vitamin D deficiency and sepsis in childhood
Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean
A106 The clinical and epidemiological aspects and prophylaxis of Lyme disease among patients who presented with tick bites to the Clinical Infectious Disease Hospital “Toma Ciorbă”
Ion Chiriac, Tiberiu Holban, Liviu Tazlavanu
A107 Drug-resistant tuberculosis in HIV infected patients
Raluca Jipa, Eliza Manea, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Adriana Hristea
A108 Kidney injury molecule-1 and urinary tract infections
Corina-Daniela Ene, Ilinca Nicolae, Roxana Simona Georgescu
A109 The impact of microbiological agents on serum gangliosides in patients with benign prostate hyperplasia
Corina-Daniela Ene, Cosmin-Victor Ene, Roxana Simona Georgescu, Marilena Ciortea , Lucreția Dulgheru, Ilinca Nicolae
A110 Toxocariasis - the experience of the Iași Infectious Diseases Hospital between 2013–2015
Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca
A111 Species of anaerobic Gram-positive cocci involved in odontogenic abscesses
Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu
A112 Clostridium difficile infection recurrences
Eliza Manea, Raluca Jipa, Adriana Hristea
A113 Differential diagnosis of staphylococcal and tuberculous osteodiscitis – case report
Adina Elena Ilie, Săftica-Mariana Pohrib, Alina Cristina Neguț, Maria-Sabina Tache, Maria Magdalena Moțoi, Oana Săndulescu, Ion Aurel Iliescu, Adrian Streinu-Cercel
A114 Severe clinical forms of respiratory syncytial virus infections
Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Daniela Pițigoi, Emilia Lupulescu
A115 Acinetobacter baumannii postoperative sepsis associated with Clostridium difficile enterocolitis in an immune suppressed elderly patient
Mirela Paliu, Manuela Curescu, Bianca Cerbu, Iosif Marincu
A116 Risk factors and their impact on psychopathology and quality of life among people living with HIV/AIDS in Romania
Fulvia Ursoiu, Mirandolina Prișcă, George Ciprian Pribac
A117 Antivirals susceptibility of influenza viruses circulating in Romania
Maria Elena Mihai, Carmen Maria Cherciu, Alina Elena Ivanciuc, Cristina Tecu, Emilia Lupulescu
A118 Retrospective study of hospitalized cases of sepsis at the Hospital Clinic of Infectious Diseases “Toma Ciorbă”
Irina Bunescu, Tiberiu Holban, Ana Pasnin, Stela Semeniuc, Raisa Popovici, Galina Chiriacov
PMCID: PMC5103241
22.  Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans 
Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment.
To identify genetic loci associated with late-onset Alzheimer disease in African Americans.
Design, Setting, and Participants
The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci.
Main Outcomes and Measures
Presence of Alzheimer disease according to standardized criteria.
Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8
Conclusions and Relevance
In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.
PMCID: PMC3667653  PMID: 23571587
BMJ Open  2012;2(3):e000873.
Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans—a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population.
To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR, MC4R, NPY2R and POMC genes.
A genetic association study.
990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans).
The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population for FTO, LEP and NPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life.
Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI.
The study highlighted SNPs in FTO and MC4R as potential genetic markers of obesity risk in South Africans. The association with two SNPs in the 3′ untranslated region of the LEP gene is novel.
Article summary
Article focus
This is a replication study aiming to reproduce BMI association findings from European cohorts in a South African population.
This study focused on genes linked to appetite control that were previously reported to show association with BMI or obesity and included FTO, LEP, LEPR, MC4R, NPY2R and POMC.
Adolescent data were used to facilitate the identification of genetic loci that predispose to obesity early in life, as it is known that overweight/obese children have an elevated risk of becoming obese adults.
Key messages
We found four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045).
Together the four SNPs account for 2.1% of the variation in log(BMI).
We also demonstrated that an accumulation of risk alleles is linked to a significant increase in BMI—individuals with seven risk alleles had an 11.0% increase in median BMI compared with those with two risk alleles.
Strengths and limitations of this study
This study provides the first preliminary evidence of the role of genetic variants in obesity risk in an adolescent black South African population.
This study was only moderately powered to detect association with BMI, and not all genes were exhaustively investigated.
TagSNP selection would have been enhanced if South African data were available for this approach.
PMCID: PMC3358621  PMID: 22614171
Genome Medicine  2010;2(3):17.
More than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology. Thus, this study employed a genome-wide association approach to identify novel variants associated with HIV MTCT.
We conducted a nested case-control study of HIV MTCT using infants of HIV(+) mothers, drawn from a cohort study of malaria and HIV in pregnancy in Blantyre, Malawi. Whole genome scans (650,000 SNPs genotyped using Illumina genotyping assays) were obtained for each infant. Logistic regression was used to evaluate the association between each SNP and HIV MTCT.
Genotype results were available for 100 HIV(+) infants (at birth, 6, or 12 weeks) and 126 HIV(-) infants (at birth, 6, and 12 weeks). We identified 9 SNPs within 6 genes with a P-value < 5 × 10-5 associated with the risk of transmission, in either unadjusted or adjusted by maternal HIV viral load analyses. Carriers of the rs8069770 variant allele were associated with a lower risk of HIV MTCT (odds ratio = 0.27, 95% confidence interval = 0.14, 0.51), where rs8069770 is located within HS3ST3A1, a gene involved in heparan sulfate biosynthesis. Interesting associations for SNPs located within or near genes involved in pregnancy and development, innate immunological response, or HIV protein interactions were also observed.
This study used a genome-wide approach to identify novel variants associated with the risk of HIV MTCT in order to gain new insights into HIV MTCT etiology. Replication of this work using a larger sample size will help us to differentiate true positive findings.
PMCID: PMC2873795  PMID: 20487506
PLoS Medicine  2007;4(12):e335.
The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) consists of DNA polymerase, connection, and ribonuclease H (RNase H) domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre) genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance.
Methods and Findings
The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. N348I increased in prevalence from below 1% in 368 treatment-naïve individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 × 10−12). N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs) M41L and T215Y/F (p < 0.001), the lamivudine resistance mutations M184V/I (p < 0.001), and non-nucleoside RTI (NNRTI) resistance mutations K103N and Y181C/I (p < 0.001). The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43–4.81). The appearance of N348I was associated with a significant increase in viral load (p < 0.001), which was as large as the viral load increases observed for any of the TAMs. However, this analysis did not account for the simultaneous selection of other RT or protease inhibitor resistance mutations on viral load. To delineate the role of this mutation in RT inhibitor resistance, N348I was introduced into HIV-1 molecular clones containing different genetic backbones. N348I decreased zidovudine susceptibility 2- to 4-fold in the context of wild-type HIV-1 or when combined with TAMs. N348I also decreased susceptibility to nevirapine (7.4-fold) and efavirenz (2.5-fold) and significantly potentiated resistance to these drugs when combined with K103N. Biochemical analyses of recombinant RT containing N348I provide supporting evidence for the role of this mutation in zidovudine and NNRTI resistance and give some insight into the molecular mechanism of resistance.
This study provides the first in vivo evidence that treatment with RT inhibitors can select a mutation (i.e., N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class resistance. Its emergence, which can happen early during therapy, may significantly impact on a patient's response to antiretroviral therapies containing zidovudine and nevirapine. This study also provides compelling evidence for investigating the role of other mutations in the connection and RNase H domains in virological failure.
Analyzing HIV sequences from a Canadian cohort, Gilda Tachedjian and colleagues identify a common mutation in a little-studied domain of reverse transcriptase that confers resistance to two drug classes.
Editors' Summary
In the 1980s, infection with the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), was a death sentence. Although the first antiretroviral drugs (compounds that block HIV's life cycle) were developed quickly, single antiretrovirals only transiently suppress HIV infection. HIV rapidly accumulates random changes (mutations) in its genetic material, some of which make it drug resistant. Nowadays, there are many different antiretrovirals. Some inhibit the viral protease, an enzyme used to assemble new viruses. Others block reverse transcriptase (RT), which makes replicates of the genes of the virus. Nucleoside/nucleotide RT inhibitors (NRTIs; for example, zidovudine—also called AZT—and lamivudine) and non-nucleoside RT inhibitors (NNRTIs; for example, nevirapine and efavirenz) interfere with the activity of RT by binding to different sites in its so-called “DNA polymerase domain,” the part of the enzyme that constructs copies of the viral genes. Highly active antiretroviral therapy (HAART), which was introduced in the mid 1990s, combines several antiretrovirals (usually a protease inhibitor and two NRTIs or an NNRTI and two NRTIs) so that the replication of any virus that develops resistance to one drug is inhibited by the other drugs in the mix. When treated with HAART, HIV infection is usually a chronic, stable condition rather than a fatal disease.
Why Was This Study Done?
Unfortunately, HIV that is resistant to drugs still develops in some patients. To improve the prevention and management of drug resistance, a better understanding of the mutations that cause resistance is needed. Resistance to RT inhibitors usually involves mutations in the DNA polymerase domain that reduce the efficacy of NRTIs (including thymidine analogue mutations—also known as TAMs—and lamivudine-resistance mutations) and NNRTIs. Blood tests that detect these resistance mutations (genotype tests) have been used for several years to guide individualized selection of HIV drugs. Recently, however, mutations outside the DNA polymerase domain have also been implicated in resistance to RT inhibitors. In this study, the researchers have used data and samples collected since the mid 1990s by Canada's British Columbia Centre for Excellence in HIV/AIDS to investigate the clinical relevance of a mutation called N348I. This mutation changes an asparagine (a type of amino acid) to an isoleucine in a region of RT known as the connection domain. The researchers have also investigated how this mutation causes resistance to RT inhibitors in laboratory tests.
What Did the Researchers Do and Find?
The researchers analyzed the first two-thirds of the RT gene in viruses isolated from a large number of the Centre's patients. Virus carrying the N348I mutation was present in less than one in 100 patients whose HIV infection had never been treated, but in more than one in 10 treatment-experienced patients. The mutation appeared early in therapy, often in viruses that had TAMs, a lamivudine-resistance mutation called M184V/I, and/or NNRTI resistance mutations. Patients treated with zidovudine and nevirapine were 2.6 times more likely to have the N348I mutation than patients not treated with these drugs. Furthermore, the appearance of the N348I mutation often coincided with an increase in viral load, although other mutations that appeared at a similar time could have contributed to this increase. When the researchers introduced the N348I mutation into HIV growing in the laboratory, they found that it decreased the susceptibility of the virus to zidovudine and to NNRTIs.
What Do These Findings Mean?
These findings show that the treatment of patients with RT inhibitors can select a drug-resistant HIV variant that has a mutation outside the enzyme's DNA polymerase domain. Because this N348I mutation, which is commonly selected in vivo and has also been seen in other studies, confers resistance to two classes of RT inhibitors and can emerge early during therapy, it could have a large impact on patient responses to antiviral regimens that contain zidovudine and nevirapine. Although these findings do not show that the N348I mutation alone causes treatment failure, they may have implications for genotypic and phenotypic resistance testing, which is often used to guide treatment decisions. At present, genotype tests for resistance to RT inhibitors look for mutations only in the DNA polymerase domain of RT. This study is the first to demonstrate that it might be worth looking for the N348I mutation (and for other mutations outside the DNA polymerase domain) to improve the ability of genotypic and phenotypic resistance tests to predict treatment outcomes.
Additional Information.
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including links to fact sheets (in English, French, and Spanish) about antiretrovirals, and chapters explaining antiretroviral resistance testing
NAM, a UK registered charity, provides information about all aspects of HIV and AIDS, including fact sheets on types of HIV drugs, drug resistance, and resistance tests (in English, Spanish, French, Portuguese, and Russian)
The US Centers for Disease Control and Prevention provides information on HIV/AIDS and on treatment (in English and Spanish)
AIDSinfo, a service of the US Department of Health and Human Services provides information for patients on HIV and its treatment
PMCID: PMC2100143  PMID: 18052601

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