Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda

Abstract

Objective: Antiretroviral therapy (ART) may interfere with replication of hepatitis B virus (HBV), raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.

Methods: We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-hepatitis B core-negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals (CIs), whereas Cox proportional regression methods were used to estimate hazard ratios (HRs).

Results: Thirty-nine HBV infections occurred over 3342 person-years, incidence 1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.49/100 person-years with ART and 2.3/100 person-years without ART [adjusted HR (aHR) 0.25, 95% CI 0.1-0.5, P < 0.001], and with lamivudine (3TC) use: 0.58/100 person-years) with 3TC and 2.25/100 person-years without 3TC (aHR 0.32, 95% CI 0.1-0.7, P = < 0.007). No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: 0.6/100 person-years with 400 copies/ml or less and 4.0/100 person-years with more than 400 copies/ml (aHR, 6.4, 95% CI 2.2-19.0, P < 0.001); and with age: 15-29 years versus 40-50 years (aHR 3.2, 95% CI 1.2-9.0); 30-39 years versus 40-50 years (aHR 2.1, 95% CI 0.9-5.3).

Conclusion: HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.

Figure 1. Flowchart of selected participants

Participant selection process: A total of 944 patients met the inclusion criteria described in the methods sections. Of these, 447 were excluded because of they had been previously been infected with HBV in their baseline samples. The remaining individuals were enrolled. The results of the laboratory tests are as summarized above. Anti-HBc = antibody to HBV core antigen; HBsAg = hepatitis B surface antigen

Fig. 2

Kaplan Meier curves for hepatitis B survival-free survival in relation to ART use. The blue and red lines represent hazards for individuals when not on ART and when on ART respectively.