Comparison of HBV-active HAART regimens in an HIV–HBV multinational cohort

Abstract

Objectives To explore factors associated with short and long-term HBV DNA suppression in a multinational cohort of HIV-HBV co-infected subjects receiving HBV-active antiretrovirals. Methods 115 HIV-HBV co-infected subjects participating in one of two global ACTG randomized clinical trials of different antiretroviral regimens received either HBV-monotherapy with either lamivudine or emtricitabine (N=56) or HBV-dual therapy with TDF plus lamivudine or emtricitabine (N=59). Associations of pre-treatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound. Results The proportion with HBV DNA<200 IU/ml was 60% (95% CI 50%–69%) at 24 weeks and 79% (95% CI 69%–88%) at 144 weeks. Pre-treatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and AST, but only pre-treatment HBV DNA remained associated with long-term suppression (P<0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual therapy group achieved HBV DNA<200 IU/mL (P=0.007). A higher proportion of hepatitis B e antigen negative subjects (n=57) achieved HBV DNA <200 IU/ml at any point, regardless of therapy group. All 12 subjects with emergence of lamivudine-resistant mutants were in the monotherapy group. Conclusions TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings where TDF may not be universally available, lamivudine or emtricitabine HBV-monotherapy is a reasonable option in patients with low HBV replication.

Lamivudine Monotherapy-Based cART Is Efficacious for HBV Treatment in HIV/HBV Coinfection When Baseline HBV DNA <20,000 IU/mL

“…This finding is similar to other developing countries where 30 to 50% had baseline HBV DNA <20,000 IU/ml 6, 15, 18 . It is in these people with HBV DNA < 20,000 IU/ml that our study demonstrates >95% HBV suppression rates for 48 weeks in both the 3TC and the TDF+3TC HIV/HBV co-infected groups.…”

“…Our multivariable analysis demonstrates that TDF is associated with HBV DNA suppression when HBV DNA ≥ 20,000 IU/ml (Table 2) or when HBeAg is negative (Supplementary Table S2) at baseline. In a recent multicenter study, Thio et al reported that in subjects with baseline HBV DNA <20,000IU/ml, monotherapy (3TC or FTC) and dual therapy (TDF+3TC or FTC) had similar efficacy in terms of HBV DNA suppression during 144 weeks of follow-up 15 . Taken together, these studies suggest that 3TC-based monotherapy might be considered in patients with HBV DNA <20,000 IU/ml or HBeAg negative when TDF cannot be safely used or accessed.…”

“…Categorical variables were analyzed by Chi square test or Fisher's exact test. To determine whether TDF+3TC is superior to 3TC-based regimen at lower HBV DNA levels, we stratified statistical analyses by baseline HBV DNA (<20,000 vs. ≥20,000 IU/ml), a level chosen based on prior studies 15 . Relative risks (RR) of factors associated with HBV DNA suppression (HBV DNA <20 IU/ml) were determined by Poisson regression with a robust error variance 16 .…”

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

“…In addition, HBV‐DNA viral loads and transaminase levels were for the most part low at treatment initiation. These conditions might have been ideal to abate the emergence of LAM resistance and have appeared to be associated with low LAM resistance rates in other treated, co‐infected populations from SSA . Considering that only one patient in this study had LAM resistance, there was an insufficient number of events to appropriately address this question.…”

Prevalence and Evolution of Renal Impairment in People Living With HIV in Rural Tanzania

“…Contributing factors to renal impairment are the high rate of patients with hypertension and diabetes mellitus, as well as co-infections [ 10 ] and chronic use of nephrotoxic drugs such as tenofovir disoproxil fumarate (TDF), atazanavir/ritonavir (ATV/r), and lopinavir/ritonavir (LPV/r) [ 11–13 ]. TDF is widely used in SSA as a first line ART due to its high efficacy and low side effects and its simultaneous effect against hepatitis B infection [ 14 , 15 ].…”