Helen M. Chun

Hepatitis B Virus Coinfection Negatively Impacts HIV Outcomes in HIV Seroconverters

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.

Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study

BackgroundTo examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007.MethodsOutcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes.ResultsAmong patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF.ConclusionsIn this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality.

Epidemiology of Hepatitis B Virus Infection in a US Cohort of HIV-Infected Individuals during the Past 20 Years

BACKGROUND The epidemiologic trends of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV)-infected patients over the past 20 years are largely unknown. METHODS Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and after HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of diagnosis of HIV infection were evaluated using logistic regression, and risk of incident HBV infection after diagnosis of HIV infection was evaluated using Cox proportional hazards models. RESULTS Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of whom 117 (11%) had chronic HBV infection. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (P < .001). The prevalence of HBV infection at the time of diagnosis of HIV infection decreased during 1989-2008 from 34% to 9% (P < .001). The incidence of HBV infection after diagnosis of HIV infection decreased from 4.0 cases per 100 person-years during the pre-highly active antiretroviral therapy (HAART) era to 1.1 cases per 100 person-years during the HAART era (P < .001); however, this incidence remained unchanged during 2000-2008 (P = .49), with >20% of HBV infections occurring after HIV infection being chronic. Decreased risk of HBV infection after diagnosis of HIV infection was associated with higher CD4 cell count and the use of HBV-active HAART. Receipt of 1 dose of HBV vaccine was not associated with reduced risk of HBV infection after diagnosis of HIV infection. CONCLUSIONS Although the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection after diagnosis of HIV infection raises concern that more-effective prevention strategies may be needed to significantly reduce the prevalence of HBV infection in this patient population.

Hepatitis B vaccination and risk of hepatitis B infection in HIV-infected individuals

Objective:To assess the association of hepatitis B virus (HBV) vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees. Design:Observational cohort study. Methods:Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan–Meier survival curves and Cox proportional hazards models. Results:During 11 632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75–2.27)/100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted hazard ratio 0.86, 95% CI 0.7–1.1; adjusted hazard ratio 1.08, 95% CI 0.8–1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (hazard ratio 0.96; 95% CI 0.56–1.64). Among 409 vaccinees with HBsAb less than 10 IU/l, 46 (11.2%) developed HBV infection compared with 11 of 217 (5.1%) vaccinees with HBsAb ≥10 IU/l (hazard ratio 0.51; 95% CI 0.3–1.0). In participants with initial HBsAb less than 10 IU/l, 16 of 46 (35%) infections were chronic, compared with none of 11 in those with initial HBsAb at least 10 IU/l (P = 0.02). Conclusion:Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.

Unusual presentations of coccidioidomycosis: a case series and review of the literature.

Abstract: Coccidioidomycosis is an emerging fungal infection of the southwestern United States. Although Coccidioides species infections are usually asymptomatic or result in a mild, flu-like illness, disseminated disease may occur in 1% of cases. While extrapulmonary disease usually involves the skin, central nervous system, bones, or joints, coccidioidomycosis is a great imitator, with the ability to infect any tissue or organ. Cases may be diagnosed outside of endemic areas, hence providers worldwide should be aware of the broad range of manifestations of coccidioidomycosis. We present a case series of unusual presentations of coccidioidomycosis including serous cavity infections with cases of pericarditis, empyema, and peritonitis, as well as unusual abscesses involving the retropharyngeal space and gluteal musculature. We provide a complete review of the literature and summarize the clinical presentations, diagnoses, and treatments of these rare forms of disseminated coccidioidomycosis. Abbreviations: CF = complement fixation, CT = computed tomography.

The Effect of Human Immunodeficiency Virus on Hepatitis B Virus Serologic Status in Co-Infected Adults

Background Factors associated with serologic hepatitis B virus (HBV) outcomes in HIV-infected individuals remain incompletely understood, yet such knowledge may lead to improvements in the prevention and treatment of chronic HBV infection. Methods and Findings HBV-HIV co-infected cohort participants were retrospectively analyzed. HBV serologic outcomes were classified as chronic, resolved, and isolated-HBcAb. Chronic HBV (CHBV) was defined as the presence of HBsAg on two or more occasions at least six months apart. Risk factors for HBV serologic outcome were assessed using logistic regression. Of 2037 participants with HBV infection, 281 (14%) had CHBV. Overall the proportions of HBV infections classified as CHBV were 11%, 16%, and 19% for CD4 cell count strata of ≥500, 200–499, and <200, respectively (p<0.0001). Risk of CHBV was increased for those with HBV infection occurring after HIV diagnosis (OR 2.62; 95% CI 1.78–3.85). This included the subset with CD4 count ≥500 cells/µL where 21% of those with HBV after HIV diagnosis had CHBV compared with 9% for all other cases of HBV infection in this stratum (p = 0.0004). Prior receipt of HAART was associated with improved HBV serologic outcome overall (p = 0.012), and specifically among those with HBV after HIV (p = 0.002). In those with HBV after HIV, HAART was associated with reduced risk of CHBV overall (OR 0.18; 95% CI 0.04–0.79); including reduced risk in the subsets with CD4 ≥350 cells/µL (p<0.001) and CD4 ≥500 cells/µL (p = 0.01) where no cases of CHBV were seen in those with a recent history of HAART use. Conclusions Clinical indicators of immunologic status in HIV-infected individuals, such as CD4 cell count, are associated with HBV serologic outcome. These data suggest that immunologic preservation through the increased use of HAART to improve functional anti-HBV immunity, whether by improved access to care or earlier initiation of therapy, would likely improve HBV infection outcomes in HIV-infected individuals.

HIV outcomes in Hepatitis B virus coinfected individuals on HAART

Background:Understanding the impact of hepatitis B virus (HBV) coinfection on HIV outcomes in the highly active antiretroviral therapy (HAART) era continues to be a critical priority given the high prevalence of coinfection and the potential for impaired immunologic, virologic, and clinical recovery. Methods:Participants from the US Military HIV Natural History Study with an HIV diagnosis on HAART and serologically confirmed HBV infection status at HAART initiation (HI) were classified into 4 HBV infection (HB) groups. HIV virologic, immunologic, and clinical outcomes were evaluated by HB status. Results:Of 2536 HIV-positive HAART recipients, with HBV testing results available to determine HB status in the HI window, HB status at HI was classified as HB negative (n = 1505; 66%), resolved HB (n = 518; 23%), isolated hepatitis B core antigen (n = 139; 6%), or chronic HB (n = 131; 6%). HIV virologic suppression and failure at 6 months or 1 year were not significantly different by HB status. A significantly faster rate of increase in CD4 cell count during the period between 4 and 12 years was observed for chronic HB relative to HB negative. Chronic and resolved HB were associated with an increased risk of AIDS/death compared with HB-negative individuals (chronic HB—hazard ratio = 1.68, 95% confidence interval: 1.05 to 2.68; resolved HB—hazard ratio = 1.61, 95% confidence interval: 1.15 to 2.25). Conclusions:HB status did not have a significant impact on HIV virologic outcomes, however, CD4 cell count reconstitution after HI and the risk of an AIDS event or death after HI may be associated with HB status.

The Timing of Hepatitis B Virus (HBV) Immunization Relative to Human Immunodeficiency Virus (HIV) Diagnosis and the Risk of HBV Infection Following HIV Diagnosis

To assess associations between the timing of hepatitis B virus (HBV) immunization relative to human immunodeficiency virus (HIV) diagnosis and vaccine effectiveness, US Military HIV Natural History Study cohort participants without HBV infection at the time of HIV diagnosis were grouped by vaccination status, retrospectively followed from HIV diagnosis for incident HBV infection, and compared using Cox proportional hazards models. A positive vaccine response was defined as hepatitis B surface antibody level ≥ 10 IU/L. Of 1,877 participants enrolled between 1989 and 2008, 441 (23%) were vaccinated prior to HIV diagnosis. Eighty percent of those who received vaccine doses only before HIV diagnosis had a positive vaccine response, compared with 66% of those who received doses both before and after HIV and 41% of those who received doses only after HIV (P < 0.01 for both compared with persons vaccinated before HIV only). Compared with the unvaccinated, persons vaccinated only before HIV had reduced risk of HBV infection after HIV diagnosis (hazard ratio = 0.38, 95% confidence interval: 0.20, 0.75). No reduction in HBV infection risk was observed for other vaccination groups. These data suggest that completion of the vaccine series prior to HIV infection may be the optimal strategy for preventing this significant comorbid infection in HIV-infected persons.

The Role of Sexually Transmitted Infections in HIV-1 Progression: A Comprehensive Review of the Literature

Due to shared routes of infection, HIV-infected persons are frequently coinfected with other sexually transmitted infections (STIs). Studies have demonstrated the bidirectional relationships between HIV and several STIs, including herpes simplex virus-2 (HSV-2), hepatitis B and C viruses, human papilloma virus, syphilis, gonorrhea, chlamydia, and trichomonas. HIV-1 may affect the clinical presentation, treatment outcome, and progression of STIs, such as syphilis, HSV-2, and hepatitis B and C viruses. Likewise, the presence of an STI may increase both genital and plasma HIV-1 RNA levels, enhancing the transmissibility of HIV-1, with important public health implications. Regarding the effect of STIs on HIV-1 progression, the most studied interrelationship has been with HIV-1/HSV-2 coinfection, with recent studies showing that antiherpetic medications slow the time to CD4 <200 cells/µL and antiretroviral therapy among coinfected patients. The impact of other chronic STIs (hepatitis B and C) on HIV-1 progression requires further study, but some studies have shown increased mortality rates. Treatable, nonchronic STIs (i.e., syphilis, gonorrhea, chlamydia, and trichomonas) typically have no or transient impacts on plasma HIV RNA levels that resolve with antimicrobial therapy; no long-term effects on outcomes have been shown. Future studies are advocated to continue investigating the complex interplay between HIV-1 and other STIs.

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Background Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. Methods and Findings From a large HIV cohort, we evaluated those who received HBV vaccine only after HIV diagnosis and had anti-HBs determination 1–12 months after the last vaccine dose. Non-response and positive response were defined as anti-HBs <10 and ≥10 IU/L, respectively. Participants were followed from date of last vaccination to clinical AIDS, death, or last visit. Univariate and multivariable risk of progression to clinical AIDS or death were evaluated with Cox regression models. A total of 795 participants vaccinated from 1986–2010 were included, of which 41% were responders. During 3,872 person-years of observation, 122 AIDS or death events occurred (53% after 1995). Twenty-two percent of non-responders experienced clinical AIDS or death compared with 5% of responders (p<0.001). Non-response to HBV vaccine was associated with a greater than 2-fold increased risk of clinical AIDS or death (HR 2.47; 95% CI, 1.38–4.43) compared with a positive response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed type hypersensitivity skin test responses (an in vivo marker of cell-mediated immunity). This association remained evident among those with CD4 count ≥500 cells/mm3 (HR 3.40; 95% CI, 1.39–8.32). Conclusions HBV vaccine responses may have utility in assessing functional immune status and risk stratificating HIV-infected individuals, including those with CD4 count ≥500 cells/mm3.