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Background & Aims: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa., Methods: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated., Results: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log 10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log 10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5)., Conclusion: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In human immunodeficiency virus (HIV)-infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults., Methods: The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIV-infected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression., Results: A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/μL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26-5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36-2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality., Conclusions: African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population., Clinical Trials Registration: NCT00495651., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Most research in sub-Saharan Africa establishes hepatitis B infection via one-time hepatitis B surface antigen (HBsAg) testing. Of 237 HIV-infected patients from two clinical trials testing HBsAg positive (MiniVidas®), 206 (86.9%) had validated serological tests using another assay (Architect). Discrepancies could be due to inactive infection, highlighting the importance of assessing hepatitis B virus infection phase., (Copyright © 2015 Elsevier Inc. All rights reserved.)

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir‐based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub‐Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)‐positive with HBV DNA ≥ 2,000 IU/ml; HBsAg‐positive with HBV DNA < 2,000 IU/ml; isolated HBcAb‐positive; resolved infection (HBsAb‐positive/HBcAb‐positive); and HBV non‐immune/vaccinated (HBcAb‐negative). We compared square‐root CD4‐cell count increases using mixed‐effect, non‐linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all‐cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti‐HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non‐immune/vaccinated. We found no significant difference in CD4 cell increases between HBV‐infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all‐cause mortality (1.9/100 person‐years, 95% Credibile Interval [CrI] = 1.0–3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = −79%, −13%), 60% (95%CrI = −82%, −12%) and 66% (95%CrI = −84%, −23%) in those who had isolated anti‐HBcAb‐positive, resolved HBV infection and HBV non‐immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti‐HBcAb‐positive serology, much like HBV non‐immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV‐related management would not be necessary for these individuals. [ABSTRACT FROM AUTHOR]

Background In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent. Methods A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d'Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as 'infection' (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or 'hepatitis' (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression. Results During a median 25 months (IQR 19–31), 17 (40%) patients consistently had 'infection', 5 (12%) consistently had 'hepatitis' and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02). Conclusions HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation. [ABSTRACT FROM AUTHOR]

Background & Aims: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S‐gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Methods: Seventy‐three antiretroviral treatment (ART)‐naïve human immunodeficiency virus (HIV)‐HBV co‐infected patients from Côte d'Ivoire, initiating anti‐HBV‐containing ART, had available HBV S‐gene sequences. S‐gene MUPIQHs were screened at ART initiation based on lower HBV‐DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Results: Genotype E was predominant (95.9%). At ART initiation, median HBV‐DNA was 7.27 log10 copies/mL (IQR = 5.26‐8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49‐4.61). Twelve S‐gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S‐gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti‐hepatitis B "e" antibody‐positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time‐to‐undetectable HBV‐DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Conclusion: Several novel S‐gene mutations were associated with reductions in replication markers among West African co‐infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification. [ABSTRACT FROM AUTHOR]