Several of the nucleos(t)ide analogues used to treat HIV also inhibit hepatitis B virus (HBV) replication, with lamivudine being the oldest of this group. Thus, prior to licensing of tenofovir, many HIV-HBV co-infected subjects received lamivudine as the only active drug against HBV as part of the anti-HIV regimen setting the stage for emergence of drug-resistant HBV. In co-infected persons, lamivudine-resistant HBV develops more rapidly than in HBV moninfected persons, but it is not known if this is true for the newer agents. Due to overlapping reading frames of the HBV Polymerase and Surface antigens, drug-resistant changes in HBV Pol can lead to mutations in the envelope. This review will discuss studies of drug-resistant HBV in HIV-infected persons including drug-resistant mutations that have been identified and clinical sequelae of these mutations.
The isolated hepatitis B core antibody (anti-HBc) pattern was generally stable, associated with human immunodeficiency virus and hepatitis C virus infection, and most commonly transitioned to or from a pattern of past infection. The isolated anti-HBc pattern likely represents resolved hepatitis B virus infection with low or undetected anti-HBs.
Background. The significance of hepatitis B core antibody (anti-HBc) without hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (anti-HBs) is unclear.
Methods. This cohort study included men enrolled in the Multicenter AIDS Cohort to determine clinical and laboratory predictors of isolated anti-HBc.
Results. A total of 2286 subjects (51% human immunodeficiency virus [HIV]–infected) were followed over 3.9 years. Overall, 16.9% (387) had at least 1 visit with isolated anti-HBc. The isolated anti-HBc pattern was stable 84% of the time, and transitioned to or from a pattern of past infection (anti-HBc and anti-HBs). Isolated anti-HBc was associated with HIV infection (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.73–2.79) and hepatitis C virus (HCV; OR, 4.21; 95% CI; 2.99–5.91). The HCV association was stronger for chronic HCV infection (OR, 6.76; 95% CI, 5.08–8.99) than for cleared HCV (OR, 3.03; 95% CI, 1.83–5.03). HIV infection, chronic HCV, and cleared HCV infection all remained associated with isolated anti-HBc in multivariable models (OR, 1.74; 95% CI, 1.33–2.29; OR, 6.24; 95% CI, 4.62–8.42; and OR, 2.77; 95% CI, 1.65–4.66, respectively). Among HIV-infected subjects, highly active antiretroviral therapy was negatively associated (OR, 0.79; 95% CI, .66–.95) with isolated anti-HBc.
Conclusions. Isolated anti-HBc is associated with HIV and HCV coinfection, especially active HCV replication, and most commonly occurs as a transition to or from the pattern of natural immunity (anti-HBc and anti-HBs). The isolated anti-HBc pattern likely represents resolved HBV infection with low or undetected anti-HBs.
hepatitis B core antibody; human immunodeficiency virus; hepatitis C; highly active antiretroviral therapy
The effect of HCV on ART response in patients in sub-Saharan Africa is unknown. We studied 1431 HIV-infected ART initiators in Jos, Nigeria of whom 6% were HCV co-infected. A similar proportion of HIV-HCV co-infected and HIV-mono-infected patients achieved HIV RNA <400 cp/ml after 24 and 48 weeks of ART (p values >0.05). Hepatotoxicity was uncommon (0.8% and 0.33% at 24 and 48 weeks, respectively), but was more common in the HIV-HCV co-infected group at 24 (aOR=19.3; 95% CI: 4.41–84.4) and 48 weeks (aOR=56.7; 95% CI: 5.03–636.92). HCV did not significantly impact ART response in this Nigerian cohort.
Hepatitis C; HIV; antiretroviral therapy; Africa
Human genome variations explain some of the heterogeneity in the immune response to antigenic stimuli. Such differences in response to hepatitis C virus (HCV) antigens can account for the ability of the immune response to clear HCV after an acute infection or to develop more rapidly progressive liver disease. Several studies have examined polymorphisms in several candidate immune-response genes for their relationship to these HCV outcomes. Results of some of these studies complement knowledge gained from immunology studies and others offer new insights into HCV biology. This review summarizes published studies on variation in immune-response genes and HCV outcomes.
human; genetics; polymorphisms; hepatitis C; fibrosis
To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multi-national cohort.
Methods and design
HIV-infected subjects enrolled in two international studies were classified as HIV-HBV co-infected or HIV monoinfected prior to ART. HIV-HBV co-infected subjects were tested for HBV characteristics, hepatitis D virus (HDV), a novel non-invasive marker of liver disease, and drug-resistant HBV. Comparisons between discrete covariates used chi-square or Fisher’s exact tests (and Jonchkheere-Terpstra for trend tests) while continuous covariates were compared using Wilcoxon Rank-Sum Test.
Of the 2105 HIV-infected subjects from 11 countries, the median age was 34 years and 63% were Black. The 115 HIV-HBV co-infected subjects had significantly higher ALT and AST values, lower body mass index, and lower CD4+ T-cell counts than HIV monoinfected subjects (median 159 cells/mL and 137 cells/mL, respectively, P=0.04). In the co-infected subjects, 49.6% had HBeAg-negative HBV, 60.2% had genotype A HBV, and 13% were HDV positive. Of the HBeAg-negative subjects, 66% had HBV DNA ≤2000 IU/ml compared to 5.2% of the HBeAg-positive subjects. Drug-resistant HBV was not detected.
Screening for HBV in HIV-infected patients in resource-limited settings is important since it is associated with lower CD4+ T-cell counts. In settings where HBV DNA is not available, HBeAg may be useful to assess the need for HBV treatment. Screening for drug-resistant HBV is not needed prior to starting ART in settings where this study was conducted.
HIV; HBV; coinfection; global
Human leukocyte antigen (HLA) genotype has been associated with probability of spontaneous clearance of hepatitis C virus (HCV). However, no prior studies have examined whether this relationship may be further characterized by grouping HLA alleles according to their supertypes, defined by their binding capacities. There is debate regarding the most appropriate method to define supertypes. Therefore, previously reported HLA supertypes (46 class I and 25 class II) were assessed for their relation with HCV clearance in a population of 758 HCV-seropositive women. Two HLA class II supertypes were significant in multivariable models that included: (i) supertypes with significant or borderline associations with HCV clearance after adjustment for multiple tests, and (ii) individual HLA alleles not part of these supertypes, but associated with HCV clearance in our prior study in this population. Specifically, supertype DRB3 (prevalence ratio (PR)=0.4; p=0.004) was associated with HCV persistence while DR8 (PR=1.8; p=0.01) was associated with HCV clearance. Two individual alleles (B*57:01 and C*01:02) associated with HCV clearance in our prior study became non-significant in analysis that included supertypes while B*57:03 (PR=1.9; p=0.008) and DRB1*07:01 (PR=1.7; p=0.005) retained significance. These data provide epidemiologic support for the significance of HLA supertypes in relation to HCV clearance.
hepatitis C virus; HLA; human leukocyte antigen; supertype
Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person’s lifetime risk of cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and in persons with a genetic variant near IL28B, the genetic basis is not well understood.
To evaluate the host genetic basis for spontaneous resolution of HCV infection.
Two-stage genome wide association study (GWAS).
13 international multicenter study sites.
919 individuals with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 individuals with serum HCV antibodies and RNA (persistence).
Frequencies of 792,721 SNPs.
Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL28B and included rs12979860 (overall per-allele OR = 0.45, P = 2.17 × 10−30) and 10 additional SNPs spanning 55,000 bases. On chromosome 6, allele frequency differences localized near genes for class II human leukocyte antigens (HLA) and included rs4273729 (overall per-allele OR= 0.59, P = 1.71 × 10−16) near DQB1*03:01 and an additional 116 SNPs spanning 1,090,000 base pairs. The associations in chromosomes 19 and 6 were independent, additive, and explain an estimated 14.9% (95% CI: 8.5–22.6%) of the variation in HCV resolution in those of European-Ancestry, and 15.8% (95% CI:4.4–31.0%) in individuals of African-Ancestry. Replication of the chromosome 6 SNP, rs4272729 in an additional 746 individuals confirmed the findings (p=0.015).
Epigenetic effects were not studied.
IL28B and HLA class II are independently associated with spontaneous resolution of HCV infection and SNPs marking IL28B and DQB1*03:01 may explain ~15% of spontaneous resolution of HCV infection.
In a cohort of men who have sex with men, most of whom were infected with human immunodeficiency virus, men chronically infected with hepatitis B were 2-fold more likely to die a liver-related death than those chronically infected with hepatitis C.
Background. It is not known whether chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C) carries a greater risk of liver-related mortality. This study compared rates of liver-related mortality between these 2 groups in the Multicenter AIDS Cohort Study (MACS).
Methods. Six hundred eighty men with CH-B (n = 337) or CH-C (n = 343) at study entry into the MACS were prospectively followed to death, last follow-up visit, or 30 March 2010, whichever came first. Four hundred seventy-two (69.4%) of these men were infected with human immunodeficiency virus type 1 (HIV-1). Causes of death were obtained from death registry matching and death certificates. Liver-related and all-cause mortality rates (MRs) were compared between groups using Poisson regression and adjusted for potential confounders and competing risks.
Results. In 6728 person-years (PYs) of follow-up, there were 293 deaths from all causes (43.5 per 1000 PYs), of which 51 were liver-related (7.6 per 1000 PYs). The all-cause MR was similar between those with CH-B and CH-C; however, the liver-related MR was significantly higher in those with CH-B (9.6 per 1000 PYs; 95% confidence interval [CI], 6.9–13.2) than those with CH-C (5.0 per 1000 PYs; 95% CI, 3.0–8.4). In the HIV-infected subgroup, which had 46 (90.2%) of the liver-related deaths, the liver-related MR remained higher from CH-B after adjusting for potential confounders (incidence rate ratio, 2.2; P = .03) and competing risks (subhazard rate ratio, 2.4; P = .02). Furthermore, among HIV-infected subjects, CD4 cell counts <200 cells/mm3 were associated with a 16.2-fold (95% CI, 6.1–42.8) increased risk of liver-related death compared with CD4 cell counts >350 cell/mm3.
Conclusions. Chronic hepatitis B carries a higher risk of death from liver disease than does CH-C, especially in HIV-infected men with greater immunosuppression.
The −1G mutant HBV is more prevalent in individuals co-infected with HIV/HBV than in individuals infected with HBV alone and in some cases is the dominant virus in circulation. This mutant is created by the deletion of a dGMP (−1G) from the guanine rich homopolymer sequence located at nts 2,085–2,090 (numbering from EcoRI site as position 1) in the HBV core gene. This deletion causes a frameshift generating a premature stop codon at 64Asn in the HBV core gene (codon 93 in the precore gene), that truncates the precore protein, precursor of the secreted hepatitis B “e” antigen (HBeAg), and the core protein which forms the viral nucleocapsid. However, the replication phenotype of the −1G mutant HBV is unknown. An in vitro cell culture model in which hepatoma cells were transiently transfected with infectious cDNAs was used to show that the −1G mutant HBV is incapable of autonomous replication and, as expected, replication was restored to wild-type (wt) levels by supplying HBV core protein in trans. Although the −1G mutation had no deleterious effect on intracellular HBV-DNA levels, high levels of −1G mutant HBV relative to wt HBV reduced virus secretion and HBeAg secretion relative to empty vector controls. Importantly, the −1G mutant HBV also caused intracellular retention of truncated precore protein in the endoplasmic reticulum (ER) and Golgi apparatus. Together, these effects may be contributing to the increased pathology observed in the setting of HIV/HBV co-infection.
HBV; HIV; co-infection; precore; HBeAg; virus replication; ER stress
To describe the safety and tolerability of zidovudine, lamivudine, and efavirenz in a low-income setting.
We conducted a prospective cohort study in a workplace HAART programme in South Africa, which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring 6-monthly pre-HAART and at 2, 6, 12, 24, 36, 48 weeks during HAART.
We assessed the incidence of specified clinical and laboratory events (AIDS Clinical Trials Group grade 3 or higher) and associated regimen changes, hospitalizations, and deaths one year before HAART initiation and one year on-HAART using person-year analysis.
Between November 2002 and October 2005, 853 subjects (98% male, median age 40 years, and median CD4 cell count at HAART initiation 186 cells/μl) met enrollment criteria. The incidence of events on-HAART was higher than pre-HAART for neutropenia and nausea/vomiting. Dizziness was common early after HAART initiation (not evaluated pre-HAART). Of those with neutropenia, 88% had no apparent clinical consequences. The incidence of anemia, hepatotoxicity, peripheral neuropathy, and rash was similar or higher pre-HAART than on-HAART. Mean hemoglobin rose during the time on-HAART and was higher at 24 and 48 weeks than at baseline (P < 0.001).
This regimen was well tolerated with a short-term increase in neutropenia, nausea, and probably neurocerebellar events. Most significantly, in contrast to reports from high-income countries, we observed a long-term improvement in the hemoglobin concentration.
Background. Although liver disease commonly causes morbidity and mortality among human immunodeficiency virus (HIV)–infected individuals, data are limited on its prevalence in HIV monoinfection. We used the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of hepatic fibrosis to characterize liver disease in the Multicenter AIDS Cohort Study.
Methods. Men were categorized based on their HIV and viral hepatitis status: uninfected (n = 1170), HIV monoinfected (n = 509), viral hepatitis monoinfected (n = 74), and HIV–viral hepatitis coinfected (n = 66).
Results. The median APRI in the HIV-monoinfected group was similar to that in the hepatitis-monoinfected group (0.42 vs 0.43; P > .05), higher than in the uninfected group (0.42 vs 0.27; P < .001) but lower than in the coinfected group (0.42 vs 1.0; P < .001). On multivariable analysis, HIV infection (1.39-fold increase [FI]; P < .001), viral hepatitis infection (1.52-FI; P < .001), and the interaction between HIV and viral hepatitis infections were independently associated with a higher APRI (1.57-FI; P < .001). Among the HIV-infected men, viral hepatitis coinfection (2.34-FI; P < .001), HIV RNA ≥100 000 copies/mL (1.26-FI; P = .007), and CD4 count ≤200 cells/mL (1.23-FI; P = .022) were independently associated with a higher APRI.
Conclusions. HIV and viral hepatitis are independently associated with an increased APRI. Further studies are needed to understand the biological basis for the association between HIV and liver disease.
(See the editorial commentary by Peters and Marston, on pages 166–8.)
Background. Understanding the impact of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) coinfection has been limited by heterogeneity of HIV disease. We evaluated HBV coinfection and HIV-related disease progression in a cohort of HIV seroconverters.
Methods. Participants with HIV diagnosis seroconversion window of ≤3 years and serologically confirmed HBV infection (HB) status were classified at baseline into 4 HB groups. The risk of clinical AIDS/death in HIV seroconverters was calculated by HB status.
Results. Of 2352 HIV seroconverters, 474 (20%) had resolved HB, 82 (3%) had isolated total antibody to hepatitis B core antigen (HBcAb), and 64 (3%) had chronic HB. Unadjusted rates (95% confidence intervals [CIs]) of clinical AIDS/death for the HB-negative, resolved HB, isolated HBcAb, and chronic HB groups were 2.43 (2.15–2.71); 3.27 (2.71–3.84); 3.75 (2.25–5.25); and 5.41 (3.41–7.42), respectively. The multivariable risk of clinical AIDS/death was significantly higher in the chronic HB group compared to the HB-negative group (hazard ratio [HR], 1.80; 95% CI, 1.20–2.69); while the HRs were increased but nonsignificant for those with resolved HB (HR, 1.17; 95% CI, .94–1.46) and isolated HBcAb (HR, 1.14; 95% CI, .75–1.75).
Conclusions. HBV coinfection has a significant impact on HIV outcomes. The hazard for an AIDS or death event is almost double for those with chronic HB compared, with HIV-monoinfected persons.
Variants near the HLA-DP gene show the strongest genome-wide association with chronic hepatitis B virus (HBV) infection and HBV recovery/persistence in Asians. To test the effect of the HLA-DP region on outcomes to HBV infection, we sequenced the polymorphic HLA-DPB1 and DPA1 coding exons and the corresponding 3′ untranslated regions (3′UTRs) in 662 individuals of European-American and African-American ancestry. The genome-wide association study (GWAS) variant (rs9277535; 550A/G) in the 3′UTR of the HLA-DPB1 gene that associated most significantly with chronic hepatitis B and outcomes to HBV infection in Asians had a marginal effect on HBV recovery in our European- and African-American samples (odds ratio [OR] = 0.39, P = 0.01, combined ethnic groups). However, we identified a novel variant in the HLA-DPB1 3′UTR region, 496A/G (rs9277534), which associated very significantly with HBV recovery in both European and African-American populations (OR = 0.37, P = 0.0001, combined ethnic groups). The 496A/G variant distinguishes the most protective HLA-DPB1 allele (DPB1*04:01) from the most susceptible (DPB1*01:01), whereas 550A/G does not. 496A/G has a stronger effect than any individual HLA-DPB1 or DPA1 allele and any other HLA alleles that showed an association with HBV recovery in our European-American cohort. The 496GG genotype, which confers recessive susceptibility to HBV persistence, also associates in a recessive manner with significantly higher levels of HLA-DP surface protein and transcript level expression in healthy donors, suggesting that differences in expression of HLA-DP may increase the risk of persistent HBV infection.
Single-nucleotide polymorphisms (SNPs) around IL28B are associated with spontaneous hepatitis C virus (HCV) clearance of genotypes 1 and 3 in white and African-American populations. This study investigated whether the IL28B SNP (rs12979860) is associated with spontaneous clearance of HCV, principally genotype 4, in 162 Egyptians (80 with clearance). The protective C allele was more common in those with spontaneous clearance (76.3% vs 57.9%; P = .0006). Individuals with clearance were 3.4 (95% confidence interval, 1.8–6.5) times more likely to have C/C genotype. Thus, IL28B plays a role in spontaneous clearance of HCV genotype 4 in North Africa.
Screening with hepatitis B surface antigen (HBsAg) is highly recommended for at-risk individuals. Mutations in the HBsAg can result in an inability to detect the virus during routine screening. We describe a hemodialysis patient found to have high levels of hepatitis B virus (HBV) DNA and HBV antibody but negative HBsAg on two routine assays.
Since 2003, U.S. organizations have recommended universal screening, rather than targeted screening, of HIV-infected persons for gonorrhea (NG) and Chlamydia (CT). Our objective was to determine whether wider testing resulting from these guidelines would produce an increase in NG/CT diagnoses.
We studied 3,283 patients receiving HIV care 1999–2007 in the Johns Hopkins Hospital HIV clinic. The two primary outcomes were: 1) the occurrence of any NG/CT testing in each year of care and 2) the occurrence of any positive result(s) in years of testing. The proportion of all patients in care who were diagnosed with NG/CT was defined as the number of patients with positive results divided by the number of patients in care. Trends were analyzed with repeated measures logistic regression.
The proportion of patients tested for NG/CT increased steadily from 0.12 in 1999 to 0.33 in 2007 (OR per year for being tested, 1.17 [1.15, 1.19]). The proportion positive among those tested decreased significantly after 2003 (OR per year 0.67 [0.55, 0.81]). The proportion of all patients in care diagnosed with NG/CT therefore remained generally stable 1999–2007 (OR per year 0.97 [0.91, 1.04]).
Universal annual screening, as implemented, did not increase the proportion of all patients in care who were diagnosed with NG/CT. Similarly low implementation rates have been reported in cross-sectional studies. If future efforts to enhance implementation do not yield increases in diagnoses, then guidelines focusing on targeted screening of high risk groups rather than universal screening may be warranted.
HIV prevention; health service research; Neisseria gonorrhoeae; Chlamydia trachomatis; screening; guidelines
Background. Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection.
Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV)–seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively.
Results. DQB1*0301 was associated with low baseline HCV load (β = −.4; 95% confidence interval [CI], −.6 to −.3; P < .00001), as well as with low odds of FIB-4–defined (odds ratio [OR], .5; 95% CI, .2–.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3–1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0–3.7; P = .04).
Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
We tested the hypothesis that a single nucleotide polymorphism (SNP) located near the interleukin-28B gene is associated with the control of hepatitis C virus and HIV-1 replication in elite controllers/suppressors. We show here that the protective genotype is not overrepresented in elite controllers/suppressors compared with HIV-1-seronegative patients and HIV-1-infected patients with viral loads more than 10 000 copies/ml. Thus, it appears that this SNP is not associated with the elite control of HIV-1 infection.
An IL28B haplotype strongly determines the outcome of natural and interferon-α treated HCV infection. To assess if the polymorphism marking the haplotype (rs12979860) also affects other interferon-α responsive chronic viral illnesses, namely hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV), we genotyped 226 individuals with HBV persistence, 384 with HBV recovery, and 2548 with or at high-risk for HIV infection. The C/C genotype of rs12979860 was not associated with HBV recovery (OR 0.99), resistance to HIV infection (0.97), or HIV disease progression (P>0.05). This IL28B SNP affects the immune response to HCV but not to HBV or HIV.
IL28B; HIV; HBV; genetics; polymorphism
Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases.
human immunodeficiency virus; liver disease; hepatitis C virus; hepatitis B virus
Treatment-induced and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-γ3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFNγ3 upregulates interferon-stimulated genes (ISGs), similar to interferon-α and β, but via a different receptor. There is also evidence that IFNγ3 affects the adaptive immune response. The IL28B genotype can be considered, along with other factors, in predicting patient responses to therapy with pegylated interferon-α and ribavirin. We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFNγ3, the clinical implications of the genetic association, and areas of future research.
IL28B; Hepatitis C Virus; Interferon Lambda; Interferon Sensitivity; HCV Treatment
An IL28B haplotype strongly determines the outcome of natural and interferon-α treated hepatitis C virus (HCV) infection. To assess whether the polymorphism marking the haplotype (rs12979860) also affects other interferon-α responsive chronic viral illnesses, namely hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 infections, we genotyped 226 individuals with HBV persistence, 384 with HBV recovery, and 2548 with or at high risk for HIV infection. The C/C genotype of rs12979860 was not associated with HBV recovery (odds ratio, 0.99), resistance to HIV infection (odds ratio, 0.97), or HIV disease progression (P>.05). This IL28B single-nucleotide polymorphism affects the immune response to HCV but not to HBV or HIV.
There are currently seven approved therapies for chronic hepatitis B infection, an increase from just three agents five years ago. This review will focus on the pharmacology, potency, and adverse events associated with immunomodulatory agents and nucleos(t)ide analogs, with an emphasis on targets of therapy within the hepatitis B lifecycle. We will also offer guidelines for the use of available anti-HBV agents and review the emerging challenges in hepatitis B management, including HBV drug resistance, its management, and the potential role of combination therapy.
Hepatitis B; Therapy; Pharmacology; Side Effects; Drug Resistance
Screening HIV-infected men for gonorrhea (GC) and Chlamydia (CT) may decrease HIV transmission and reduce the incidence of pelvic inflammatory disease in female partners. This study determined GC/CT testing rates in a clinical HIV cohort before and after 2003 when the U.S. Centers for Disease Control and Prevention issued guidelines for GC/CT screening.
First GC/CT testing episodes were identified for all men enrolling in a Baltimore HIV clinic 1999–2007. Multivariate Cox and logistic regression were used to assess clinical and demographic factors associated with being tested and with having a positive result.
Among 1110 men, the rate of GC/CT testing upon clinic enrollment increased from 4.0% prior to 2003 to 16.5% afterward, and the rate of ever being tested increased from 34.2% to 49.1% (P <0.001 for both comparisons). Among men with same sex contact, 10% of first testing episodes included extragenital sites. Among the 342 men ever-tested, 5.2% had positive results on first testing. Predictors of testing included enrolling after 2003, younger age, frequent visits, and black race. Predictors of a positive test result included CD4 count ≥200 cells/mm3 and younger age.
GC/CT testing rates among men increased substantially after the 2003 guidelines but remain low. Disseminating existing evidence for GC/CT screening and promoting operational interventions to facilitate it are warranted.
health service research; gonorrhea; Chlamydia; screening; HIV secondary prevention