Background:  In a Nigerian HIV/hepatitis B virus (HBV) -co-infected cohort, we showed that hepatitis B was associated with lower CD4 counts and higher HIV RNA prior to ART. We hypothesized that high HBV DNA levels would influence pre-ART HIV stage and ART-related hepatotoxicity, but that it would not affect ART response.

Methods: We tested our hypothesis in HIV⁺/HCV^– patients who initiated ART through PEPFAR in Nigeria. We compared HIV parameters between a control group of HIV⁺/HBV^–/HCV^– (HIV only) patients and several HIV/HBV-co-infected (hepatitis B surface antigen [HBsAg]⁺) groups stratified according to HBV DNA levels (≥20,000 IU/mL) and HBeAg status. Comparisons were made at baseline and after months 3 and 6 of ART using nonparametric tests for continuous variables and Fisher's exact tests for categorical variables. Hepatotoxicity was defined according to AIDS Clinical Trials Group (ACTG) definitions.

Results:  There were 1305 HIV-only and 264 HIV/HBV patients, of which 263 (99.6%) and 232 (87.9%) were tested for hepatitis B virus e antigen (HBeAg) and HBV DNA, respectively. Median baseline CD4 count (cells/mm³) was lower in the HIV/HBV group with high HBV DNA (85) than in the HIV only or the HIV/HBV with low HBV DNA (130 and 127, respectively; p = 0.0005). Stratification by HBeAg revealed that the median baseline CD4 count in the HBeAg^–, low HBV DNA was similar to the HIV only group (129 and 130 cells, respectively); all other groups had lower median baseline counts. The median baseline HIV RNA was similar between the HIV/HBV groups with high and low HBV DNA (91,413 and 90,435 copies/mL), which was significantly higher than the HIV only group (55,947 copies/mL; p = 0.002). After 6 months of ART, neither HBV DNA nor HBeAg status altered the percent with HIV RNA <400 copies/mL. CD4 counts increased in all groups at 6 months, but those with high HBV DNA had lower median CD4 counts (216 vs 250 for low HBV DNA and 247 for HIV only, p = 0.03). HBeAg status did not alter this relationship. The high HBV DNA group had significantly higher median baseline alanine aminotransferase (ALT) (p = 0.0002) and the greatest cumulative hepatotoxicity by month 6 (5.6% vs 1.4 to 1.5%, p = 0.03).

Conclusions:  In this HIV/HBV-co-infected Nigerian cohort, high HBV DNA levels were associated with lower baseline CD4 counts and increased risk for hepatotoxicity on ART. High HBV DNA levels did not impair immunological and virological responses with 6 months of ART, but CD4 counts remained lower in those with high HBV DNA. Further studies are needed to understand the impact of HBV on HIV therapy and management.