Effect of hepatitis B virus (HBV) surface‐gene variability on markers of replication during treated human immunodeficiency virus‐HBV infection in Western Africa

Abstract

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.

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

“…Indeed, several studies have demonstrated that decreased genetic complexity, less frequent or specific mutations, and less frequent deletions in the “a” determinant are correlated with clearing HBsAg [ 60 , 61 , 62 ]. One study has examined the broader spectrum of S -gene mutations in co-infected individuals prior to initiating anti-HBV containing ART, including mutations on the “a” determinant, and failed to find any mutations linked to HBsAg-seroclearance [ 63 ]. Hence, S -gene mutations might not affect rates of HBsAg-seroclearance during treatment.…”

Mortality in relation to hepatitis B virus (HBV) infection status among HIV‐HBV co‐infected patients in sub‐Saharan Africa after immediate initiation of antiretroviral therapy

“…In cohort studies of people with HIV in the U.S., where HBV is not endemic, the most common HBV subgroup noted was non‐immune/vaccinated (66–74%) followed by resolved HBV infection (20–23%) and isolated anti‐HBcAb (3.5–6%) 6,17 . Possible explanations for these observed subgroup differences among people with past or present HBV infection include: (1) timing of HBV infection, with co‐infected individuals in sub‐Saharan Africa being mostly infected with HBV long before HIV infection and co‐infected individuals in the U.S. more likely to be in the ‘window phase’ of acute HBV infection; (2) immunologic differences, which may produce a different proportion of individuals due to the timing of waning anti‐HBsAb levels following resolved HBV infection; and to a lesser extent (3) genetic differences in HBV, which may result in HBsAg that escapes detection due to mutations on the surface gene 37 …”