Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model

Objectives Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.Methods We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA<300 copies/mL to >106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).Results Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.Conclusions We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management

Trends in HIV Testing, the Treatment Cascade, and HIV Incidence among Men Who Have Sex with Men in Africa: A Systematic Review and Meta-Regression Analysis

Background Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment including socio-economic disadvantages, stigma, and criminalization that increase their vulnerability to HIV acquisition and transmission and undermine progress towards ending AIDS. This systematic review explores progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa. Methods We searched Embase, Medline, Global Health, Scopus, and Web of Science from January 1980-March 2022 for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and/or HIV incidence among MSM in Africa. We pooled surveys using Bayesian generalized linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men. Findings Of 8,992 articles identified, we included 148 unique studies published from 2005-2022. HIV testing increased over time in Central/Western and Eastern Africa and in 2020, we estimate that 88% (95% credible interval (CrI) 57-97%) of MSM had tested in the past 12 months, but 66% (19-94%) of MSM living with HIV knew their HIV status, although this is probably underestimated given non-disclosure. Current ART use increased over time in Central/Western (ORyear=1.4, 95%CrI 1.1-2.0, N=8) and Eastern/Southern Africa (ORyear=1.4, 1.0-1.8, N=17) and in 2020 we estimate that 75% (18-98%) of MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence viral suppression increased, and in 2020 we estimate that only 62% (12-95%) of MSM living with HIV were virally suppressed. HIV incidence among MSM did not decrease over time (IRRyear=1.0, 0.7-1.3, N=38) and remained high in 2020 (5.4 per 100 person-years, 0.9-33.9) and substantially higher (27-150 times higher) than among all men. Interpretation No decreases in HIV incidence have been observed among MSM in Africa over time, despite some increases in HIV testing and ART use. Achieving the UNAIDS 95-95-95 targets for diagnosis, treatment, and viral suppression equitably for all requires renewed focus on this key population. Combination interventions for MSM are urgently required to reduce disparities in HIV incidence and tackle the social, structural, and behavioural factors that make MSM vulnerable to HIV acquisition. Funding US National Institutes of Health, UK Medical Research Council, Canadian Institutes of Health Research, Fonds de Recherche du Quebec - Sante

Higher Risk of Mortality in HIV-HBV Co-Infected Patients from Sub-Saharan Africa Is Observed at Lower CD4 \textsuperscript+ Cell Counts

International audienceBackground Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 + cell counts in this association is poorly defined. We aimed to determine whether HIV\textendash HBV co-infection influences changes in CD4 + cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4 + . Methods 2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4 + cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4 + counts ≤q350, 351\textendash 500, >500/mm 3 and were compared between HBV-status groups as incidence rate ratios (IRR). Results At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA 500/mm 3 (adjusted-IRR = 1.07, 95% CI = 0.01\textendash 4.91). Conclusion Despite no effect of HBV-infection on CD4 + levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4 + is <500/mm 3

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial

Background: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. Methods: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. Findings: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3–5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9–5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1–9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39–0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. Interpretation: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. Funding: National Research Agency on AIDS and Viral Hepatitis (ANRS)