HIV dominates T-cell immune responses in HIV-HBV co-infection and is associated with increased HIV reservoir transcription.

Due to the effectiveness of antiretroviral therapy (ART), Human Immunodeficiency Virus (HIV) infection is now managed as a chronic condition. However, people with HIV (PWH) remain susceptible to co-infections, including Hepatitis B virus (HBV), with 15% of PWH in Africa being co-infected. While co-infections may accelerate disease progression and increase AIDS-related mortality, their effects on T-cell responses and HIV reservoir size are unclear. This study compared T-cell responses in people with HIV-HBV co-infection, HIV or HBV alone, and assessed the effects of HBV on the HIV reservoir size. We screened 390 archived samples from virologically suppressed (viral load < 50 copies/mL) PWH and identified 31 individuals with HIV-HBV co-infection. Peripheral blood mononuclear cells (PBMCs) were analyzed at baseline and following stimulation to assess activation and exhaustion markers (CD25, CD38, CD69, HLA-DR, and PD-1) by flow cytometry. Inflammatory cytokines were quantified using a 12-plex Luminex panel. HIV reservoir size was determined by RT-PCR measurements of proviral DNA and unspliced RNA. The prevalence of HIV-HBV co-infection was 7.9% (31/390). At baseline, unstimulated T cells showed increased CD38+HLA-DR- expression on both CD4+ and CD8+ T cells in people with HIV-HBV co-infection and HIV alone compared with HBV mono-infection. PD-1 expression on CD4+ T cells was also higher in the HIV-HBV and HIV mono-infection groups than with HBV alone. After stimulation, CD69 expression on both CD4+ and CD8+ T cells was higher in the HIV-HBV and HIV-only groups than in HBV alone. CD8+ T cells from individuals with co-infection showed higher PD-1 expression, while CD4+ PD-1 expression was similar across groups. CD38⁺HLA-DR⁺ co-expression on CD4⁺ T cells was increased in the HIV-HBV and HIV mono-infection groups but was similar on CD8⁺ T cells across groups. Pro- and anti-inflammatory cytokine levels were highest in the co-infected group. The usRNA reservoir transcriptional activity level was significantly higher in HIV-HBV co-infection (p = 0.022) while cell-associated DNA remained the same for both groups. Among individuals with HIV-HBV co-infection who have achieved virological suppression, while HIV appears to be the main driver of T cell responses, HBV can result in a more active reservoir.