Hepatitis B virus clinical and virologic characteristics in an HIV perinatal transmission study in sub-Saharan Africa.

OBJECTIVES: To describe the clinical and virologic characteristics of HIV-HBV coinfection, including the predictors of high maternal HBV viral load in pregnant women with HIV in sub-Saharan Africa (SSA). METHODS: HPTN 046 was a HIV perinatal transmission clinical trial evaluating infant nevirapine vs. placebo. Women-infant pairs ( n  = 2016) were enrolled in SSA from 2007 to 2010; 1579 (78%) received antiretrovirals (ARV). Maternal delivery samples were retrospectively tested for hepatitis B surface antigen (HBsAg), and if positive, were tested for hepatitis B e antigen (HBeAg) and HBV viral load (VL). High HBV VL was defined as ≥10 6  IU/ml. RESULTS: Overall, 4.4% (88/2016) had HBV co-infection, with geographic variability ranging from 2.4% to 8.7% ( P  < 0.0001); 25% (22/88) were HBeAg positive with prevalence in countries ranging from 10.5% to 39%. Fifty-two percentage (40/77) of those with HBV received ARV, the majority (97%) received 3TC as the only HBV active agent. HBeAg positivity was associated with high maternal HBV VL, odds ratio (OR) 37.0, 95% confidence interval (CI) 5.4-252.4. Of those with high HBV VL, 40% (4/10) were receiving HBV active drugs (HBV-ARV). HBV drug resistance occurred in 7.5% (3/40) receiving HBV-ARV. CONCLUSIONS: In SSA, HBV co-infection is common in pregnant women with HIV. HBsAg and HBeAg prevalence vary widely by country in this clinical trial cohort. HBeAg is a surrogate for high HBV viral load. HBV drug resistance occurred in 7.5% receiving HBV-ARV with lamivudine as the only HBV active agent. These findings reinforce the importance of HBsAg screening and early treatment with two active agents for HBV.

Evaluation of and implications for a novel hepatitis C e-consult direct-to-treatment pilot program.

A Hepatitis C (HCV) e-Consult Direct-To-Treatment (DTT) program managed by midlevel providers was developed at the Veteran Affairs Greater Los Angeles Healthcare System (VAGLAHS) which provided remote referral and, in some, remote management of HCV. DTT patients were more likely to be initiated on HCV treatment compared to standard of care (SOC), lending support for similar programs of remote engagement in HCV care.

Comparison of Antiretroviral Therapies in Pregnant Women Living With Human Immunodeficiency Virus and Hepatitis B Virus: A Randomized Controlled Trial.

OBJECTIVE: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01061151.

Patient acceptability of, and attitudes towards, hepatitis B cure research - A scoping review and identification of knowledge gaps.

Functional cure, defined as durable loss of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA suppression off therapy, is an increasingly important goal in the treatment of chronic hepatitis B. Although novel treatments aimed at achieving functional cure are being developed and tested in clinical trials, it is important to assess the perspectives of people living with HBV towards these potential treatments and their participation in HBV functional cure research. We have performed a scoping review that revealed that there is limited knowledge regarding patient perspectives of HBV functional cure research and then identified gaps in knowledge for further investigation. Our work highlights the need for further studies in patient perspectives in HBV functional cure research.

Brief Report: Impact of Antiretroviral Regimen on Pregnancy and Infant Outcomes in Women With HIV/ HBV Coinfection.

BACKGROUND: There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV. METHODS: The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly. RESULTS: Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ). CONCLUSION: With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.

Hepatotoxicity and Liver-Related Mortality in Women of Childbearing Potential Living With Human Immunodeficiency Virus and High CD4 Cell Counts Initiating Efavirenz-Containing Regimens.

BACKGROUND: Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens. METHODS: In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/µL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation. RESULTS: Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]). CONCLUSIONS: Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.

Maternal HBV Viremia and Association With Adverse Infant Outcomes in Women Living With HIV and HBV.

BACKGROUND: There is limited information on perinatal outcomes in HIV-hepatitis B virus (HBV) coinfection. METHODS: HIV Prevention Trials Network (HPTN) 046 was a randomized double-blind placebo-controlled trial of perinatal transmission that evaluated 6 months of infant nevirapine versus placebo among breast-fed infants. Women living with HIV and their infants enrolled in sub-Saharan Africa from 2007 to 2010; 78% received antiretroviral therapy (ART). Maternal samples were tested for hepatitis B surface antigen (HBsAg). High and low HBV viral load (VL) was defined as ≥106 IU/mL and <106 IU/mL. The association between HIV-HBV coinfection and maternal and infant outcomes was assessed using multivariate (MV) logistic and Cox regression. RESULTS: Among 2025 women, 88 (4.3%) had HBV. HIV-HBV women with high HBV VL had lower median CD4, versus HIV alone or HIV-HBV women with low HBV VL [320, 490 and 434 cells/mm3, respectively (P < 0.007)]. In MV analysis, adjusted for maternal CD4, age and maternal ART, infants born to women with high HBV VL were more likely to be low birth weight (LBW), versus HIV+/HBV- and low HBV VL women: [30% (3/10) vs. 10% (194/1953) vs. 6% (5/78), respectively, P = 0.03). High HBV VL was associated with HIV perinatal transmission [(hazard ratio 6.75 (95% confidence interval (CI): 1.86 - 24.50)]. There was no impact on infant mortality or maternal outcomes at 18 months. CONCLUSIONS: In HIV-HBV women, high HBV viral loads increase the risk of LBW and potentially HIV perinatal transmission. Reduction of antepartum HBV viremia may have beneficial effects beyond the prevention of HBV perinatal transmission.

Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era.

PURPOSE OF REVIEW: The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. RECENT FINDINGS: The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.