Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.

Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Vinikoor MJ ，Hamusonde K ，Muula G ，Asombang M ，Riebensahm C ，Chitundu H ，Sunkuntu-Sichizya V ，Bhattacharya D ，Sinkala E ，Lauer G ，Chung R ，Mbewe W ，Egger M ，Bosomprah S ，Wandeler G ... -  《-》

Hepatic Flare Following Effective Antiretroviral Therapy Is Associated With HBsAg Seroclearance in HBV/HIV-1 Co-Infection.

Little is known about the clinical significance of hepatic flare following effective antiretroviral therapy (ART) on HBsAg seroclearance and prognosis in HBV/HIV co-infection. This observational cohort study recruited HBV/HIV-1 co-infected patients from the China National Free Antiretroviral Treatment Program. We obtained longitudinal information on demographic characteristics, clinical indicators, and treatment outcomes. Hepatic flare was defined as an elevation of ALT of more than five times the upper limit of the normal range without an upsurge of HBV DNA or HBsAg at any time point between ART initiation and 12 months. Among the 1354 enrolled patients, 98.7% received two anti-HBV drugs containing ART and 95.1% achieved good viral control. Hepatic flare was observed in 88 (6.5%) patients and was more frequent in those with lower baseline immune function but subsequently enhanced immune reconstitution. Over a median follow-up of 4.7 years, we observed 99 HBsAg seroclearance, 9 hepatic events, 6 HIV-associated malignancy, 3 non-HIV-associated malignancy, and 3 all-cause mortality. The 3-, 5-, and 10-year cumulative incidence of HBsAg seroclearance was 6.4%, 8.9%, and 12.9%, respectively. Compared to patients without hepatic flare, patients with hepatic flare had significantly higher rates of HBsAg seroclearance (13.6% vs. 6.9%, p = 0.018) but had no recorded adverse outcome. Multivariate analysis with different models indicated that hepatic flare was independently associated with HBsAg seroclearance especially in patients with low immune function, normal ALT, and high levels of HBV DNA and HBsAg at baseline. In HBV/HIV-1 co-infection, hepatic flare following effective ART is associated with HBsAg seroclearance. HBV-specific T cells immune reconstitution may represent a potential mechanism which deserves further investigation.

Lin W ，He Y ，Gu F ，Hu F ，Yu H ，Li H ，Liu C ，Tang X ，Cai W ，Li L ... -  《-》

Clinical outcomes of untreated adults living with chronic hepatitis B in The Gambia: an analysis of data from the prospective PROLIFICA cohort study.

Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis. Between Dec 7, 2011, and Jan 24, 2014, we implemented the prospective PROLIFICA cohort study in The Gambia. Participants with chronic hepatitis B aged 16 years or older were recruited after large-scale, community-based HBV screening; blood bank-based HBV screening in Edward Francis Small Teaching Hospital, Banjul; and prospective follow-up of HBsAg-positive individuals via historical, population-based HBsAg serosurveys in two rural villages (Keneba and Manduar). Participants underwent HBV serology and other laboratory tests, fasting FibroScan, and abdominal ultrasound. Survival data were collected between Dec 7, 2011, and Aug 17, 2021. Between Oct 9, 2018, and Aug 17, 2021, all HBsAg-positive participants enrolled in the 2011-14 cohort were invited for a reassessment. For this analysis, we included HBsAg-positive people and excluded all participants who were eligible for treatment according to the 2012 European Association for the Study of the Liver (EASL) criteria at baseline and those who were treated irrespective of treatment eligibility. The primary outcome was all-cause mortality, assessed in all treatment-ineligible and treatment-naive participants with follow-up data. The secondary outcome, analysed in those who were reassessed, was disease progression, defined as becoming eligible for antivirals per 2017 EASL criteria; having an increase in liver fibrosis of at least one stage; or having a clinical diagnosis of hepatic decompensation or hepatocellular carcinoma. 943 HBsAg-positive people with chronic hepatitis B were recruited to the PROLIFICA study. Of these 943, 58 (6%) fulfilled 2012 EASL treatment eligibility criteria at baseline, 35 (4%) were ineligible for treatment but received antiviral therapy, and 44 (5%) were immediately lost to follow-up. Thus, 806 (85%) participants were analysed for the primary outcome (486 [60%] were male and 320 [40%] were female). After a median follow-up of 6·11 years (IQR 5·34-6·80), 708 (88%) participants were confirmed to be alive at last surveillance, 71 (9%) were lost to follow-up and were censored, and 27 (3%) died, giving an all-cause mortality rate of 582 per 100 000 person-years (95% CI 399-849). Of the 27 people who died, five (19%) had liver-related deaths. Of 708 participants confirmed to be alive, 544 (77%) attended follow-up and were assessed for the secondary outcome. Disease progression occurred in 36 (7%) participants: five (1%) became newly eligible for antiviral therapy per EASL 2017 criteria without liver fibrosis progression; 18 (3%) had liver fibrosis progression alone; 13 (2%) had liver fibrosis progression and newly fulfilled the treatment criteria; and none had hepatic decompensation or developed hepatocellular carcinoma. In multivariable analysis adjusted for sex and age, only a baseline HBV DNA of 20 000 IU/mL or more, compared with the baseline HBV DNA of 2000 IU/mL or lower as the reference, was significantly associated with liver disease progression (odds ratio 5·39, 95% CI 1·37-21·23). Among people with chronic hepatitis B who were ineligible for antiviral therapy in The Gambia, all-cause mortality and liver disease progression were low. The clinical benefit of expanding antiviral therapy in this subgroup of patients remains uncertain. European Commission, Medical Research Council UK Research and Innovation, and Gilead Sciences.

Ndow G ，Shimakawa Y ，Leith D ，Bah S ，Bangura R ，Mahmoud I ，Bojang L ，Ceesay A ，Drammeh S ，Bola-Lawal Q ，Lambert G ，Hardy P ，Ingiliz P ，Haddadin Y ，Vo-Quang E ，Chevaliez S ，Cloherty G ，Bittaye SO ，Lo G ，Toure-Kane C ，Mendy M ，Njie R ，Chemin I ，D'Alessandro U ，Thursz M ，Lemoine M ... -  《The Lancet Gastroenterology & Hepatology》

Hepatitis B virus (HBV) viremia despite tenofovir disoproxil fumarate-containing antiretroviral therapy in persons with HBV/HIV coinfection.

The goal of treatment of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is suppression of both viruses; yet incomplete HBV suppression on tenofovir (TFV) disoproxil fumarate (TDF)-based antiretroviral therapy (ART) is common. This study investigated TFV resistance-associated mutations (RAMs) in individuals with HBV/HIV coinfection with viremia on TDF/lamivudine (3TC)-containing ART. Samples from individuals with HBV DNA levels ≥20 IU/mL in a cross-sectional study of 138 persons with HBV/HIV coinfection in Ghana were analyzed in the present study. HBV was sequenced for RAM analysis. TFV-diphosphate (TFV-DP) concentration in peripheral blood mononuclear cells (PBMCs) was used to assess ART adherence level. Nine of 138 participants (6.5 %) had detectable HBV DNA levels ≥20 IU/mL while on ART. Seven of the nine participants had TFV-DP concentrations commensurate with 7 doses per week, and six had suppressed HIV RNA. Phylogenetic analysis revealed that eight sequences were HBV genotype E, with one genotype E/A recombinant. Ten previously-reported TFV RAMs were present in the study samples; eight were wild-type for HBV genotype E. The non-genotype-E-wild-type point mutations M267L and K333Q were found in two and one patients, respectively. No 3TC RAMs were found. HBV viremia despite high adherence to TDF/3TC-based ART may be associated with the presence of TFV RAMs. These findings highlight the need for enhanced resistance monitoring and further research to examine the clinical significance of reported TFV RAMs. Individuals with HBV/HIV coinfection and TFV resistance on TDF-based ART may need alternative treatment strategies.

Ryan P ，Odegard E ，Meeds H ，Lartey M ，Ganu VJ ，Tachi K ，Yang H ，Ojewale O ，Boamah I ，Obo-Akwa A ，Antwi K ，Anderson PL ，Blackard JT ，Kwara A ... -  《-》

Frequent hepatitis B surface antigen (HBsAg) clearance during tenofovir therapy in persons with HIV/hepatitis B virus coinfection.

Hepatitis B surface antigen (HBsAg) loss is a rare event among persons with hepatitis B virus (HBV) monoinfection but seems to happen more frequently in people with HIV (PWH). We assessed the proportion of PWH/HBV coinfection who experienced HBsAg loss during long-term tenofovir-therapy and evaluated its association with quantitative HBsAg (qHBsAg) levels at tenofovir start. All Swiss HIV Cohort Study participants with two or more positive HBsAg measurements more than 6 months apart, and at least 4 years of tenofovir-containing antiretroviral therapy (ART), were considered. Our main outcomes were the loss of HBsAg during the first 2 years of tenofovir therapy and until the last available follow-up. We explored the association between qHBsAg levels at tenofovir start and HBsAg loss using multivariable logistic regression adjusted for potential confounders. A total of 272 PWH and HBV coinfection were included. Median age was 41 years (IQR 36-46) and 81% (221) were men. At tenofovir start, 62% (169/272) received prior HBV active therapy, 49% (110/224) were hepatitis B e antigen (HBeAg)-positive, 82% (222/272) had detectable HBV DNA (median 4.0 log10 IU/mL, IQR 2.1-7.5) and 19% (46/242) had low qHBsAg, defined as <1000 IU/mL. HBsAg loss was observed in 7% (19/272) of participants during the first 2 years of tenofovir-containing ART and in 16% (43/272) after a median follow-up time of 8.4 years (IQR 2.6-15.8). At the last follow-up, 59% (16/27) of those with HBsAg loss had seroconverted for detectable anti-HBs antibodies. In multivariable analyses, low qHBsAg at tenofovir start (OR 5.3, 95% CI 1.6-17.8) was a significant predictor of HBsAg loss. We found high rates of HBsAg loss in PWH and HBV coinfection on long-term tenofovir-containing ART, most of whom had low qHBsAg at tenofovir start.

Béguelin C ，Surial B ，Hofmann E ，Begré L ，Munting A ，Günthard HF ，Stöckle M ，Bernasconi E ，Schmid P ，Calmy A ，Suter-Riniker F ，Rauch A ，Wandeler G ，Swiss HIV Cohort Study (SHCS) ... -  《-》