A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers whose efforts often go unrecognized. AIDS Research and Therapy has been blessed by the support of highly qualified peer reviewers and would like to show its appreciation by thanking the following for their assistance with review of manuscripts for the journal in 2012.
Intestinal parasites are a major concern in most developing countries where HIV/AIDS case are concentrate and almost 80% of AIDS patients die of AIDS-related infections. In the absence of ART, HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic parasites. But this prevalence has dramatically decreased in countries where antiretroviral agents are widely available. Therefore, the aim of this study was to assess the prevalence of intestinal parasite and risk factor among pre- ART and on ART adult HIV/ AIDS patients attending ART clinic in Dessie hospital.
A comparative cross-sectional study was conducted among pre-ART and on ART adult HIV/AIDS patients of Dessie Hospital. A total of 272 (136 from each group) study subjects were selected by using systematic random sampling. Stool sample was collected and processed using direct wet mount, formol-ether concentration technique and modified Ziehl-Neelson staining techniques. A structured questionnaire was used to collect data on Sociodemographic & associated risk factors. Data was entered and analyzed by using SPSS 16 software and logistic regressions were applied to assess any association between explanatory factors and outcome variables.
The overall prevalence of IP in pre-ART and on-ART was 39% and 17.6%, respectively with significant decrease of intestinal parasite in the ART era (p < 0.001). All Cryptosporidium spps infections were found in the pre-ART patients and significantly associated for lower CD4 <200cells/mm3. Absence of toilet (AOR = 7.57; 95% CI = 1.3,44.22), source of water (AOR = 6.03; 95% CI = 1.14,31.98), living condition (AOR = 13.29, 95% CI = 5.14, 34.35); WHO stage (AOR = 6.06; 95% CI = 2.49,14.74) and ART status (AOR = 7.55; 95% CI = 3.24,17.59) have significant association with prevalence of intestinal parasite.
The overall prevalence of IP was differ by ART status and opportunistic parasite like cryptosporidium spps were found in low CD4 counts in ART naive patients. This study identified some environmental and some clinical finding as determinant factor for IP infections. Therefore, public health measures and adherence to ART should be strengthened to improve the quality of life of these patients.
Intestinal parasite; ART; CD4
The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP). We compared the virological outcomes of (1) HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV); and (2) HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls).
This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a) two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b) a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation.
A total of 559 patients were stratified into three groups: (a) Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161); (b) Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI) backbone therapy for a median of 7 days (n=82); and (c) Control, in which the subjects were naïve to antiretroviral therapy (n=316). The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4) and Control (6.6). However, differences were not statistically significant.
Among the patients who had an acute allergic reaction to first-line NVP-based therapy and later began an EFV-based regimen, virological outcomes resulting from a staggered interruption of treatment (with a continuation of NRTI backbone therapy for 7 days after discontinuing NVP) did not differ from those of the patients who began an EFV-based regimen as their initial therapy (Control). However, the virological failure of Simultaneous Interruption was possibly higher than those of Control and Staggered Interruption.
Nevirapine hypersensitivity or allergy; Efavirenz; Simultaneous interruption; Staggered interruption; Thai
Despite progress in the development of combined antiretroviral therapies (cART), HIV infection remains a significant challenge for human health. Current problems of cART include multi-drug-resistant virus variants, long-term toxicity and enormous treatment costs. Therefore, the identification of novel effective drugs is urgently needed.
We developed a straightforward screening approach for simultaneously evaluating the sensitivity of multiple HIV gag-pol mutants to antiviral drugs in one assay. Our technique is based on multi-colour lentiviral self-inactivating (SIN) LeGO vector technology.
We demonstrated the successful use of this approach for screening compounds against up to four HIV gag-pol variants (wild-type and three mutants) simultaneously. Importantly, the technique was adapted to Biosafety Level 1 conditions by utilising ecotropic pseudotypes. This allowed upscaling to a large-scale screening protocol exploited by pharmaceutical companies in a successful proof-of-concept experiment.
The technology developed here facilitates fast screening for anti-HIV activity of individual agents from large compound libraries. Although drugs targeting gag-pol variants were used here, our approach permits screening compounds that target several different, key cellular and viral functions of the HIV life-cycle. The modular principle of the method also allows the easy exchange of various mutations in HIV sequences. In conclusion, the methodology presented here provides a valuable new approach for the identification of novel anti-HIV drugs.
HIV; Drug resistance; Drug screening; Lentiviral vectors
The relationship between HIV serostatus disclosure and sexual risk behavior is inconsistent across studies. As men who have sex with men (MSM) are emerging as the key affected population in Bangkok, Thailand with reported HIV prevalence of 30%, we assessed whether HIV disclosure is associated with protected sex in this population.
A risk behavior questionnaire was administered using Audio Computer-Assisted Self-Interviewing (ACASI) to determine whether HIV serostatus disclosure was associated with protected sex in 200 HIV-positive MSM in Bangkok. HIV serostatus disclosure to the most recent sexual partner prior to or at the time of the sexual encounter was assessed. Protected sex was defined as insertive or receptive anal intercourse with a condom at the most recent sexual encounter.
The mean age was 30.2 years, CD4 was 353 cells/mm3, and one-third was on antiretroviral therapy. At the most recent sexual encounter, HIV serostatus disclosure rate was low (26%); 60.5% of subjects had not discussed their serostatus at all, while 5.5% had not revealed their true serostatus. Seventeen percent reported unprotected anal intercourse and about half had sex with their primary partners. The serostatus of the most recent sexual partner was HIV-positive in 19.2%, HIV-negative in 26.4%, and unknown in 54.4% of subjects. There was no association between disclosure and protected sex, with 41 of 48 (85.4%) disclosers and 104 of 126 (82.5%) of non-disclosers reported protected sex (p = .65). Subjects with HIV-positive partners were less likely to report protected sex overall (20 of 33, 60.6%) compared to those with HIV negative (82 of 96, 85.4%) or unknown (41 of 45, 91.1%) partners (p = .001). Age (27-32 years vs. ≤26 years, p = .008), primary partner status (p < .001), and HIV-positive serostatus of sexual partner (p < .001) were significantly associated with disclosure in the multivariate analyses.
Rates of HIV disclosure to sexual partners by HIV-positive MSM in Bangkok are low. Despite low rates of HIV serostatus disclosure, most HIV-positive MSM reported protected sex with their partners at risk for infection. Future studies should focus on understanding barriers to disclosure and factors driving risk behavior amongst MSM in Thailand.
HIV-positive; Serostatus disclosure; Men who have sex with men; Thailand
The benefits of antiretroviral therapy (ART) cannot be experienced if they are not taken as prescribed. Yet, not all causes of non-adherence are dependent on the patient. Having to pay for medication reduces adherence rates. Non- adherence has severe public health implications which must be addressed locally and globally. This paper seeks to describe the trends in adherence rates reported in Cameroon and to investigate the determinants of adherence to ART in the Cameroon Mobile Phone SMS (CAMPS) trial.
We conducted a systematic review of electronic databases (PubMed, Google Scholar, Web of Science, CINAHL, EMBASE and PSYCINFO) for publications on adherence to ART in Cameroon (from January 1999 to May 2012) and described the trend in reported adherence rates and the factors associated with adherence. Data were extracted in duplicate. We used multivariable analyses on the baseline data for 200 participants in the CAMPS trial to determine the factors associated with adherence in four models using different measures of adherence (more than 90% or 95% on the visual analogue scale, no missed doses and a composite measure: 100% on the visual analogue scale, no missed doses and all pills taken on time).
We identified nine studies meeting our inclusion criteria. Adherence to ART in Cameroon has risen steadily between 2000 and 2010, corresponding to reductions in the cost of medication. The factors associated with adherence to ART in Cameroon are grouped into patient, medication and disease related factors. We also identified factors related to the health system and the patient-provider relationship. In the CAMPS trial, education, side effects experienced and number of reminder methods were found to improve adherence, but only using multiple reminder methods was associated with better adherence in all the regression models (Adjusted Odds Ratio [AOR] 4.11, 95% Confidence Interval [CI] 1.89, 8.93; p<0.001; model IV).
Reducing the cost of ART is an important aspect of ensuring adequate adherence rates. Using multiple reminder methods may have a cumulative effect on adherence to ART, but should be investigated further.
Adherence; Antiretroviral therapy; Cameroon; Reminder methods; CAMPS
To investigate anti-infective treatments in HIV-infected surgical patients during the perioperative period.
A retrospective study of sepsis and surgical site infections (SSIs) was conducted in 266 HIV-infected patients. The patients were divided into 3 groups based on CD4+ T cells counts in the preoperative period: group A (0–199 cell/ul), group B (200–349 cell/ul) and group C ([greater than or equal to] 350 cell/ul). When the CD4 count was below 350 cells/uL, anti-retrovirus therapy was started. For patients whose preoperative CD4 counts were [less than or equal to] 200 cells/uL, preoperative antibiotic medication was started.
Patients in group A were more likely to get sepsis than patients in the other two groups (p0.01). Among 82 patients with clean wounds, only one patient got SSIs. All patients with dirty wounds had acquired SSIs after surgery. There were only 6 patients dead at 30 days after surgery, a death rate of 2.3%. Sepsis appeared in 110 patients (41%).
Complete evaluation of surgical risk and suitable perioperative anti-infective treatment may lead to better outcome for HIV-infected surgical patients.
HIV/AIDS; Surgical site infection; Sepsis; Anti-infective treatment
Peripheral neuropathy (PN) which is the most common neurological complication of HIV infection is under recognised and undertreated especially in resource limited settings. This ailment which has a negative impact on the quality of life of HIV/AIDS patients exists in different clinical patterns of which HIV-associated Sensory neuropathy (HIV-SN) is the most common affecting up to two thirds of patients with advanced disease in some settings. In Cameroon where HIV is a major public health problem, the burden of HIV-SN has not yet been well defined.
Using the Brief Peripheral Neuropathy Screening (BPNS) tool validated by the AIDS Clinical Trial Group (ACTG) we carried out a cross sectional study to determine the prevalence of HIV-SN and its associated factors among HIV-1 patients at the Douala General Hospital between 1st July and 31st October 2011. HIV-SN was defined as the presence of neuropathic symptoms and at least an abnormal perception of vibrations of a 128Hz tuning fork on the great toe or abnormal ankle reflexes or both and expressed as a percentage of the study population.
Out of 295 patients studied, 21% had HIV-SN. In HIV-SN patients the median duration of HIV infection was 79.8 months (IQR 46 – 107.5) and their median CD4 count 153cells/μL (IQR 80 – 280). Patient recall and clinical chart review showed that, 83.9% had neuropathic symptoms prior to HAART initiation and 16.1% after HAART initiation. Low CD4 count, history of alcohol intake and history of anti-tuberculosis treatment were strongly associated with HIV-SN (AOR 2.5, 2.8 and 2.9 respectively).
HIV-SN is common among patients with advanced HIV infection in Cameroon. This simple diagnostic tool (BPNS) should therefore be routinely used to detect those with HIV-SN or at risk so as to minimise the negative impact it has on their quality of life.
HIV-associated sensory neuropathy; HIV; CD4 count; Peripheral neuropathy
Human APOBEC3G is a host defense factor that potently inhibits HIV replication. We hypothesize that HIV-infected children with a genetic variant of APOBEC3G will have a more rapid disease progression.
Antiretroviral therapy (ART)-naïve children, aged 1–12 years old with CD4 15-24% and without severe HIV-related symptoms were enrolled. The children had CD4% and absolute CD4 counts every 12 weeks and HIV-RNA every 24 weeks until 144 weeks. ART was started when CD4% declined to < 15% or AIDS-related events developed.
APOBEC3G genetic variants were performed by PCR-based restriction fragment length polymorphism techniques from peripheral blood mononuclear cells. Random-effect linear regression analysis was performed to correlate APOBEC3G genotypes and disease progression.
147 children, 35% male, with a median (IQR) age of 6.5 (4.3-8.8) years were enrolled. CDC N:A:B were 1:63:36%. Median baseline values were 20% for CD4% 605 cells/mm3 for CD4 count and 4.7 log10copies/mL for HIV-RNA.
The frequencies of APOBEC3G genotypes AA (186H/H), AG (186H/R), GG (186R/R) were 86%, 12%, and 2% respectively. The APOBEC3G genotype GG was associated with a significant decline in CD4% -5.1% (−8.9 to −1.2%), p<0.001, and CD4 counts −226 (−415 to −34) cells/mm3, p<0.001 by random-effect liner regression analysis. No significant associations of APOBEC3G genotypes with HIV-RNA changes overtime (p=0.16) or progression to CDC B and C (p=0.49) were observed.
APOBEC3G genotype GG was significantly associated with a more rapid decline in CD4. APOBEC3G’s antiviral effects on HIV disease progression in children should be further explored.
APOBEC3G; Treatment-naïve; HIV-infected children; Disease progression; PREDICT
Whilst there have been studies on the risks and outcomes of MRSA colonization and infections in HIV-positive patients, local data is limited on the risk factors for MRSA colonization among these patients. We undertook this study in a tertiary HIV care centre to document the risk factors for colonization and to determine the prevalence of MRSA colonization among HIV-positive outpatients in Singapore.
This was a cross-sectional study in which factors associated with MRSA positivity among patients with HIV infection were evaluated. A set of standardized questionnaire and data collection forms were available to interview all recruited patients. Following the interview, trained nurses collected swabs from the anterior nares/axilla/groin (NAG), throat and peri-anal regions. Information on demographics, clinical history, laboratory results and hospitalization history were retrieved from medical records.
MRSA was detected in swab cultures from at least 1 site in 15 patients (5.1%). Inclusion of throat and/or peri-anal swabs increased the sensitivity of NAG screening by 20%. Predictors for MRSA colonization among HIV-positive patients were age, history of pneumonia, lymphoma, presence of a percutaneous device within the past 12 months, history of household members hospitalized more than two times within the past 12 months, and a most recent CD4 count less than 200.
This study highlights that a proportion of MRSA carriers would have been undetected without multiple-site screening cultures. This study could shed insight into identifying patients at risk of MRSA colonization upon hospital visit and this may suggest that a risk factor-based approach for MRSA surveillance focusing on high risk populations could be considered.
Methicillin-resistant Staphylococcus auerus; HIV; Risk factors; Colonization
Dyslipidaemia and dysglycaemia have been associated with exposure to ritonavir-boosted protease inhibitors. Lopinavir/ritonavir, the most commonly used protease inhibitor in resource-limited settings, often causes dyslipidaemia. There are contradictory data regarding the association between lopinavir concentrations and changes in lipids.
To investigate associations between plasma lopinavir concentrations and lipid and glucose concentrations in HIV-infected South African adults.
Participants stable on lopinavir-based antiretroviral therapy were enrolled into a cross-sectional study. After an overnight fast, total cholesterol, triglycerides, and lopinavir concentrations were measured and an oral glucose tolerance test was performed. Regression analyses were used to determine associations between plasma lopinavir concentrations and fasting and 2 hour plasma glucose, fasting cholesterol, and triglycerides concentrations.
There were 84 participants (72 women) with a median age of 36 years. The median blood pressure, body mass index and waist: hip ratio were 108/72 mmHg, 26 kg/m2 and 0.89 respectively. The median CD4 count was 478 cells/mm3. Median duration on lopinavir was 18.5 months. The median (interquartile range) lopinavir concentration was 8.0 (5.2 to 12.8) μg/mL. Regression analyses showed no significant association between lopinavir pre-dose concentrations and fasting cholesterol (β-coefficient −0.04 (95% CI −0.07 to 0.00)), triglycerides (β-coefficient −0.01 (95% CI −0.04 to 0.02)), fasting glucose (β-coefficient −0.01 (95% CI −0.04 to 0.02)), or 2-hour glucose concentrations (β-coefficient −0.02 (95% CI −0.09 to 0.06)). Lopinavir concentrations above the median were not associated with presence of dyslipidaemia or dysglycaemia.
There was no association between lopinavir plasma concentrations and plasma lipid and glucose concentrations.
Lopinavir; Hypercholesterolaemia; Hypertriglyceridaemia; Impaired glucose metabolism; Antiretroviral therapy; Pharmacokinetics
Data on lipid profile abnormalities among patients receiving highly active antiretroviral treatment in Ethiopia are very limited. The aim of this study was to determine the prevalence of dyslipidemia and characteristics of lipid profiles among patients living with human immunodeficiency virus (HIV) using first-line highly active antiretroviral therapy (HAART) in Southern Ethiopia.
This cross sectional comparative group study was conducted between March and May 2012, and included 113 HIV infected patients treated for a minimum of one year with first-line HAART regimens that included Efavirenz and Nevirapine (HAART group) and others 113 who had never received HAART (pre-HAART group). Serum lipid profiles were determined after overnight fasting and dyslipidemia was assessed according to the United State National Cholesterol Education program-III guideline. For statistical analysis Chi-square, student’s t-test, and logistic regression were used using Statistical Package for Social Sciences (SPSS) Version 20.
Ninety-three (82.3%) of HAART and 87 (76.9%) pre-HAART patients had at least one laboratory abnormality, which is compatible with a diagnosis of dyslipidemia. Total cholesterol ≥ 200 mg/dl occurred in 43.4% of HAART and 15.9% pre-HAART patients (p=<0.0001), whereas HDL-cholesterol below 40 mg/dl occurred in 43.4% and in 63.7% respectively, (p=0.002). The LDL-cholesterol ≥ 130 mg/dl occurred in 33.6% of HAART and 15% pre-HAART patients (p=0.001), while triglycerides ≥ 150 mg/dl occurred in 55.8% and 31.0% respectively, (p=0.001). Receiving of HAART was significantly and positively associated with raised total cholesterol, LDL-cholesterol, and triglycerides. The adjusted odds ratio (95% CI) of HAART-treated vs. pre-HAART was 3.80 (1.34-6.55) for total cholesterol ≥ 200 mg/dl; 2.64 (1.31-5.32) for LDL- cholesterol ≥ 130 mg/dl and 2.50 (1.41-4.42) for triglycerides ≥150 mg/dl.
Use of first-line antiretroviral therapy regimens that contain Efavirenz and Nevirapine were associated with raised total cholesterol, LDL-cholesterol, and triglycerides, an established atherogenic lipid profiles. Lipid profiles should be performed at baseline before commencement of antiretroviral therapy and then periodically through treatment follow-up to monitor any rising trends.
Dyslipidemia; HIV/AIDS; Antiretroviral therapy; Ethiopia
Opiate substitution treatment has been associated with better adherence to lifesaving antiretroviral medications, but the impact of other substance abuse treatment on adherence is unknown.
In this study, 215 patients who had been in adherence-focused research studies provided electronically-measured adherence data and a measure of whether the patient had recently been in substance abuse treatment. Recent engagement in substance abuse treatment was independently associated with significantly higher adherence, after covarying for recent substance use and other factors potentially affecting adherence.
The findings suggest that substance abuse treatment is associated with better adherence. Potential mechanisms by which substance abuse treatment improves adherence, such as more stability or more future-orientation, require further study.
Medication adherence; AIDS; Substance abuse; Treatment
Metabolic Syndrome (MetS) is based on the same individual components, but has received several amendments to the original definition. In this study, we verified the prevalence of metabolic syndrome according to different criteria, and the impact of each component on the diagnostic.
This cross-sectional study enrolled HIV infected patients from a HIV/AIDS reference Center in southern Brazil. Metabolic syndrome was identified according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII), the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, and using a standardized questionnaire and blood testing.
A sample of 1240, out of 1295, HIV-infected patients was enrolled. Males were on average older, more educated, and had shorter time since the HIV diagnosis. The population attributable risk (PAR) for waist circumference explained 80% of the prevalence among men and women (AHA/NHLBI criteria). Triglycerides had the highest impact on prevalence of metabolic syndrome according to all criteria, independently of age, skin color and HAART use, among men.
In this large sample of HIV infected patients, the overall prevalence of metabolic syndrome, under either classification, was noticeable and the AHA/NHLBI definition accounted for the highest prevalence.
Metabolic syndrome; Population attributable risk; HIV/AIDS; NCEP-ATPIII; IDF; AHA/NHLBI; Waist circumference
HIV infection among children, particularly those under 24 months of age, is often rapidly progressive; as a result guidelines recommend earlier access to combination antiretroviral therapy (cART) for HIV infected children. Losses to follow-up (LTFU) and death in the interval between diagnosis and initiation of ART profoundly limit this strategy. This study explores correlates of LTFU and death prior to ART initiation among children.
The study is based on 337 HIV-infected children enrolled into care at an urban centre in The Gambia, including those alive and in care when antiretroviral therapy became available and those who enrolled later. Children were followed until they started ART, died, transferred to another facility, or were LTFU. Cox proportional hazards regression models were used to determine the hazard of death or LTFU according to the baseline characteristics of the children.
Overall, 223 children were assessed as eligible for ART based on their clinical and/or immunological status among whom 73 (32.7%) started treatment, 15 (6.7%) requested transfer to another health facility, 105 (47.1%) and 30 (13.5%) were lost to follow-up and died respectively without starting ART. The median survival following eligibility for children who died without starting treatment was 2.8 months (IQR: 0.9 - 5.8) with over half (60%) of all deaths occurring at home. ART-eligible children less than 2 years of age and those in WHO stage 3 or 4 were significantly more likely to be LTFU when compared with their respective comparison groups. The overall pre-treatment mortality rate was 25.7 per 100 child-years of follow-up (95% CI 19.9 - 36.8) and the loss to programme rate was 115.7 per 100 child-years of follow-up (95% CI 98.8 - 137). In the multivariable Cox proportional hazard model, significant independent predictors of loss to programme were being less than 2 years of age and WHO stage 3 or 4. The Adjusted Hazard Ratio (AHR) for loss to programme was 2.06 (95% CI 1.12 – 3.83) for being aged less than 2 years relative to being 5 years of age or older and 1.92 (95% CI 1.05 - 3.53) for being in WHO stage 3 or 4 relative to WHO stage 1 or 2.
Earlier enrolment into HIV care is key to achieving better outcomes for HIV infected children in developing countries. Developing strategies to ensure early diagnosis, elimination of obstacles to prompt initiation of therapy and instituting measures to reduce losses to follow-up, will improve the overall outcomes of HIV-infected children.
Paediatrics; HIV; Pre-antiretroviral therapy; Loss to follow-up; Mortality; Retention; Sub-Saharan Africa
The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009.
There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02).
Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.
HIV; Intensive care; HAART
In resource limited settings non-availability of CD4 count facility at the site could adversely affect the ART roll out programme. Point of care CD4 enumerating equipments can make the CD4 count available at the site of care and improve the patients’ management considerably. This study is aimed at determining the utility of a Point of Care PIMA CD4 analyzer (Alere, Germany) in the field settings in India.
The blood samples were collected from 1790 participants at 21 ART centers from different parts of the country and tested using PIMA and the reference methods (FACSCalibur, FACSCount and CyFlow SL3). The paired finger prick and venous blood samples from 175 participants were tested by the PIMA CD4 Analyzer and then by FACSCalibur.
The CD4 counts obtained by PIMA CD4 analyzer showed excellent correlation with the counts obtained by the reference methods; for venous blood the Pearson’s r was 0.921, p < 0.001 and the relative bias was 0.2% (range: -42 to 42%) and for finger prick samples, the Pearson’s r was 0.856 and the relative bias was −9.1% (range: -46% to 27%). For CD4 ranges; <250, 251–350, 351–500 and >500 cells/mm3, the differences in the median CD4 counts obtained by the reference method and the PIMA analyzer were not significant (P > 0.05) and the relative bias were low (−7 to 5.1%). The Intermachine comparison showed variation within the acceptable limit of%CV of 10%.
In the field settings, the POC PIMA CD4 analyzer gave CD4 counts comparable to the reference methods for all CD4 ranges. The POC equipment could identify the patients eligible for ART in 91% cases. Adequate training is necessary for finger prick sample collection for optimum results. Decentralization of CD4 testing by making the CD4 counts available at primary health centers, especially in remote areas with minimum or no infrastructure would reduce the missed visits and improve adherence of the patients.
CD4+ T-cell count; HIV; Point-of-care; PIMA CD4 analyzer
The true prevalence of HIV and other sexually transmitted diseases among street children in Nepal is virtually unknown while information on related behavioural risk factors in this population is non-existent. The risk of HIV infection among street children and adolescents may be especially high due to their marginalized social and economic conditions. This study was conducted to determine the prevalence of HIV infection among a sample of street children and youth of Kathmandu and to identify risk factors associated with HIV infection in this group.
A sample of street children and youth was recruited based on the purposive sampling of ten streets in Kathmandu, Nepal, known to have a high density of street children and youth. A total of 251 street children (aged 11–16 years) and youth (aged 17–24 years) were enrolled, with informed consent, from November, 2008 through June, 2009. Most of the participants (95%) were male. Case status was determined by serological assessment of HIV status; data on risk factors were obtained using structured survey interviews. HIV prevalence and rates of a number of behavioural risk factors suspected to play a role in HIV transmission among street children and youth were determined, including unprotected sex, intravenous drug use, and other risky sex and substance use behaviours.
Among the 251 children and youth, we found an overall HIV prevalence of 7.6%. As the sample size of females was small (n = 13) and the behavioural risk factors are likely to be quite different for boys and girls, we conducted separate analyses by gender. As our small sample of females is unlikely to be representative and lacks power for statistical testing, our report focuses on the results for the males surveyed.The strongest behavioural risk factor to emerge from this study was intravenous drug use; 30% of the male subjects were injecting drug users and 20% of those were HIV positive. Furthermore, frequency of drug injection was a highly significant predictor with a dose–response relationship; males reporting occasional injection drug use were nearly 9 times more likely to be HIV positive than never users, while weekly drug injectors had over 46 times the risk of non-users, controlling for exposure to group sex, the only other significant risk factor in the multivariate model.
This sample of street children and youth of Kathmandu has a nearly 20-fold higher prevalence of HIV infection than the general population of Nepal (0.39%). The children and youth engage in number of high risk behaviours, including intravenous drug use, putting them at significant risk of contracting HIV and other sexually transmitted infections.
HIV prevalence; Behavioural risk factors; Intravenous drug use; Street children; Kathmandu; Nepal
This study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam.
We conducted a retrospective chart review of all patients with laboratory confirmed Penicilliummarneffei infection admitted to the National Hospital for Tropical Diseases in Hanoi, Vietnam, between July 2006 and September 2009.
127 patients with P. marneffei infection were identified. All were HIV-infected; median CD4+ T-cell count was 24 cells/μl (IQR:12-48); 76% were men. Common clinical features were fever (92.9%), skin lesions (82.6%), hepatomegaly (61.4%), lymphadenopathy (40.2%), weight loss (59.1%) and cough (49.6%). Concurrent opportunistic infections were present in 22.0%; half of those had tuberculosis. Initial treatment regimens were: itraconazole or ketoconazole capsule (77.2%), amphotericin B (20.5%), and fluconazole (1.6%). In-hospital mortality was 12.6% and showed no significant difference in patients treated with itraconazole (or ketoconazole) and amphotericin B (p = 0.43). Dyspnea, ascites, and increased LDH level were independent predictors of mortality. No seasonality was observed.
The clinical features, treatments and outcomes of HIV-associated P. marneffei infection in northern Vietnam are similar to those reported in other endemic regions. Dyspnea was an important predictor of mortality. More patients were treated with itraconazole than amphotericin B and no significant difference in treatment outcome was observed. It would be of clinical value to compare the efficacy of oral itraconazole and amphotericin B in a clinical trial.
Penicillium Marneffei; Penicillosis; HIV; Opportunistic Infections
The 2012 International Symposium on HIV and Emerging Infectious Diseases (ISHEID) provided a forum for investigators to hear the latest research developments in the clinical management of HIV and HCV infections as well as HIV-1 reservoirs and cure research. Combined anti-retroviral therapy (c-ART) has had a profound impact on the disease prognosis of individuals living with HIV-1 infection. However, although these anti-retroviral regimens are able to reduce plasma viremia to below the limits of detection for sustained periods of time, there is a rapid recrudescence in plasma viremia if treatment is interrupted. Therefore, despite this potent anti-retroviral suppression, HIV-1 is able to persist within the infected individual. The main 2012 ISHEID theme was, hence “searching for an HIV cure”. In this report we not only give details on this main topic of the 2012 ISHEID but also summarize what has been discussed in the areas of HIV epidemiology, access to care, antiretroviral therapy management and recent progress in the therapy of HCV infection in patients with HIV.
HIV pandemic; HIV cure; HIV reservoirs; Antiretroviral therapy; HCV coinfection; Access to care; New anti-HCV drugs
CCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS. Countries in Sub-Saharan Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of a country’s circulating HIV strains to guide the impending use of CCR5 antagonists.
To determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya.
Blood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIV env fragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of the env sequences was done using Geno2pheno
[co-receptor], and phylogenetic relationships determined using CLUSTALW and Neighbor Joining method.
A total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistical significant associations were observed between cell tropism and CD4+ status, patient gender, age, or treatment option. There was a tendency for more X4 tropic strains being in the treatment experienced group than the naive group: Of 46 treatment experiencing participants, 14(30%) harboured X4, compared with 4(19%) of 21 of the treatment-naïve participants, the association is however not statistically significant (p = 0.31). However, a strong association was observed between subtype D and CXCR4 co- receptor usage (p = 0.015) with 6(60%) of the 10 subtype D being X4 tropic and 4(40%) R5 tropic.
HIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.
Co-receptor usage; HIV-1; Sub-type D
The high cost of CD4 count estimation in resource-limited countries is a major challenge in initiating patients on highly active antiretroviral therapy (HAART). Therefore, assessment of inexpensive and simple laboratory diagnostic marker is mandatory to diagnose immuno-suppression.
To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected patients.
Materials and Methods
In this cross sectional study, 400 ART-naive HIV-positive patients enrolled in Gondar University Hospital, from March 2011 to May 2011, were tested for CD4 count & TLC. The cutoffs were determined as: 200 cells/μL for CD4 count and 1200 cells/μL for TLC by using BD FACS count and CELL DYN 1800 Flow Cytometrys respectively. Spearman correlation between TLC and CD4 cell count were assessed. Sensitivity, specificity, positive and negative predictive values for different age a group, TLC ≤1200 was computed for CD4 count ≤200 cells/cu.mm.
Among 400 ART naive HIV infected patients, 278 (69.5%) were females. The mean age of the study participants was 33.7. TLC and CD4 count were positively correlated (r = 0.33, p = 0.001). A TLC of ≤1200 cells/m m3 was found to have a sensitivity (32.86%), specificity (95.33%), PPV (79.7%), and NPV (71.9%) for predicting a CD4 count of <200 cells/mm3.
This study showed that low sensitivity and specificity of TLC as a surrogate measure for CD4 count. Moreover, CD4 cell counts of < 200 cells/mm3 were found in 96 cases (24%) with TLCs of ≤1200 cells/mm3. Thus, 1 in 4 individuals would have been deprived of needed treatment. Therefore, we recommend keep on expansion of access to CD4 counter.
Total lymphocyte count; CD4 counts; HAART; Surrogate marker
Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens.
A retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks.
Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002).
Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.
Pediatric HIV; Drug resistance; Second-line antiretroviral therapy; Protease-inhibitors; Resource limited settings
The aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART.
We performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4–8 months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ≥100/mm3 from baseline to month 4–8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome.
The early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p = 0.01) or NNRTI (88.5% versus 84.7%; p = 0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ≥100/mm3 CD4+ increase within 8 months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p = 0.003) and NNRTI (63.7% versus 74.7%; p < 0.001). Regarding late CD4+ increase, positive HCV Ab appeared to impair immune reconstitution in terms of absolute CD4+ T-cell count increase both in patients treated with PI/r (p = 0.013) and in those treated with NNRTI (p = 0.002). This was confirmed at a multivariable analysis up to 12 months of follow-up.
In this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12 months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.
HIV; HCV; HAART