Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China

Abstract

In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15–20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV.

Treatment advantage in HBV/HIV coinfection compared to HBV monoinfection in a South African cohort

“…We identified a patient with phenotypic evidence of 3TC-resistant HBV in our cohort, congruent with evidence for the consistent selection of resistance among individuals on 3TC monotherapy [42], and in keeping with another African study that documented a high prevalence of 3TC resistance among coinfected patients [4]. Tenofovir resistance is less well substantiated, and can be difficult to confirm phenotypically due to the slow rate of HBV DNA suppression after institution of therapy [26]; however, there are reports confirming the potential for resistance to this agent (as previously reviewed [8,34]).…”

Hepatitis B infection in HIV-1-infected patients receiving highly active antiretroviral therapy in Lomé, Togo: Prevalence and molecular consequences

“…It is known that the HBV viral load is related to the presence of HBeAg, [4] and lamivudine alone is less effective in reducing the HBV viral load. [26,27] We also found that a higher level of education was associated with active HBV replication. This may be because patients with a lower level of education tend to acquire HBV infection earlier during childhood, through horizontal transmission among toddlers, and have therefore lost HBeAg, whereas patients with a higher level of education tend to acquire HBV later in life through sexual exposure.…”

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

“…This is compared to other HIV/HBV co-infection studies, which did not stratify by baseline HBV DNA, that have shown approximately 30-60% achieving HBV DNA suppression with 3TC monotherapy at 48 weeks 19-21 . A recent study from China with a small number of HIV/HBV co-infected subjects demonstrated that 3TC monotherapy was associated with higher rates of 3TC-resistant HBV compared to TDF+3TC 22 , but in this study, the authors did not stratify their analyses with baseline HBV DNA levels. 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.…”