Immunological Efficacy of Tenofovir Disproxil Fumarate-Containing Regimens in Patients with HIV-HBV Co-Infection: A Meta-Analysis

Abstract

Background: Hepatitis B virus (HBV) co-infection is common in HIV patients. HIV infection modifies the natural course of HBV infection, leading to a faster progression of liver-related morbidity and mortality than for HBV mono-infection. This systematic review and meta-analysis evaluates current clinical evidence for the use of oral TDF-based treatments in patients with HIV-HBV co-infection. Methods: We performed a comprehensive literature search in PubMed and Web of Science. Supplementary searches were conducted in Google Scholar and Clinicaltrials.gov. We conducted a random-effects meta-analysis, using the event rate (ER) to estimate the incidence of HBV seroconversion. Subgroup meta-analysis was performed to assess the moderate effects of demographic and disease-related variables on HBsAg loss. This review is registered in the PROSPERO database (CRD42018092379). Findings: We included 11 studies in the review. The immunological effects of oral Tenofovir Disproxil Fumarate (TDF)-based PrEP treatment in patients with HIV-HBV co-infection were 0.249 (95% CI: 0.155-0.376, p<0.001) for HBeAg loss, 0.237 (95% CI 0.145-0.362, p<0.001) for HBeAg conversion, 0.073 (95% CI 0.044-0.119, p<0.001) for HBsAg loss and 0.055 (95% CI 0.02-0.142, p<0.001) for HBsAg conversion, respectively. The factors associated with HBsAg loss were baseline HBV viral load, participant location and history of exposure to LAM/FTC (all p<0.05). A trend toward a negative relationship baseline CD4+ T-cell count and HBsAg loss was observed (p=0.078). Interpretation: Oral TDF-containing regimens are effective for seroconversion in patients with HIV-HBV co-infection. Well-designed prospective cohort studies and large randomized clinical trials (RCTs) are now required to investigate potential predictors and biological markers of HBV remission in patients with HIV-HBV co-infection. Funding Statement: This work was supported by the National 13th 287 Five-Year Grand Program on Key Infectious Disease Control (2018ZX10301407-005-001 to T.Y., 2017ZX10202102-005-003 to B.S., 2017ZX10202101-004-001 to T.Z.), the National Natural Science Foundation of China (NSFC, 81772165 to B.S., 81571973 to H.W.), the NSFC-NIH Biomedical collaborative research program (81761128001 to H.W.), the Beijing Municipal of Science and Technology Major Project (D161100000416003 to H.W.), the Funding for Chinese overseas talents returning to China in 2016 (to B.S.), the Beijing Key Laboratory for HIV/AIDS Research (BZ0089). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This review is registered in the PROSPERO database CRD42018092379).