Abacavir/Lamivudine versus Tenofovir/Emtricitabine with Atazanavir/Ritonavir for Treatment-naive Japanese Patients with HIV-1 Infection: A Randomized Multicenter Trial

Abstract

Objective To compare the efficacy and safety of fixed-dose abacavir/lamivudine (ABC/3TC) and tenofovir/ emtricitabine (TDF/FTC) with ritonavir-boosted atazanavir (ATV/r) in treatment-naïve Japanese patients with HIV-1 infection. Methods A 96-week multicenter, randomized, open-label, parallel group pilot study was conducted. The endpoints were times to virologic failure, safety event and regimen modification. Results 109 patients were enrolled and randomly allocated (54 patients received ABC/3TC and 55 patients received TDF/FTC). All randomized subjects were analyzed. The time to virologic failure was not significantly different between the two arms by 96 weeks (HR, 2.09; 95% CI, 0.72-6.13; p=0.178). Both regimens showed favorable viral efficacy, as in the intention-to-treat population, 72.2% (ABC/3TC) and 78.2% (TDF/ FTC) of the patients had an HIV-1 viral load <50 copies/mL at 96 weeks. The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms (adverse event: HR 0.66; 95% CI, 0.25-1.75, p=0.407) (regimen modification: HR 1.03; 95% CI, 0.33-3.19, p=0.964). Both regimens were also well-tolerated, as only 11.1% (ABC/3TC) and 10.9% (TDF/FTC) of the patients discontinued the allocated regimen by 96 weeks. Clinically suspected abacavir-associated hypersensitivity reactions occurred in only one (1.9%) patient in the ABC/3TC arm. Conclusion Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC, this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients, such as the Japanese population.

Raltegravir and Abacavir/Lamivudine in Japanese Treatment-Na&iuml;ve and Treatment-Experienced Patients with HIV Infection: a 48-Week Retrospective Pilot Analysis

“…The HEAT study showed that the antiviral effect of ABC/3TC was not inferior to that of TDF/FTC (3). In a report comparing ABC/3TC with TDF/FTC in Japanese HIV-infected patients, ABC/3TC was found to be a safe and efficacious initial regimen for Japanese population (9). In the SHIELD trial, the number of cases was small to make any conclusions about the efficacy of ABC/3TC for the HIV-infected patients with viral loads ＞100,000 copies/mL; our study is the first report on the efficacy and safety of ABC/3TC for Japanese patients with high viral loads.…”

Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment‐naïve HIV‐1‐infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

“…The limited number of randomized trials in ART‐naïve patients showed inconsistent responses to 3TC or FTC in combination with a boosted PI. These trials were all confounded because the second NRTI combined with either 3TC or FTC also differed (TDF, abacavir or zidovudine) . The evidence to support the equivalent recommendation of 3TC and FTC with TDF in HIV‐1 treatment guidelines appears insufficient.…”

Early Virologic Response to Abacavir/Lamivudine and Tenofovir/Emtricitabine During ACTG A5202

“…5 In a small study of 109 subjects with ATV/r as the third drug, the time to virologic failure was not significantly different in those randomized to ABC/3TC versus TDF/FTC (HR=2.1; 95% CI: 0.7, 6.1), although nearly 100% of patients had a baseline viral load of <100,000 copies/mL. 15 Additionally, subgroup analyses from the randomized THRIVE and SPRING-2 studies did not show a difference in efficacy between subjects given ABC/3TC vs. TDF/FTC, although the NRTIs were investigator-selected in these studies and not allocated through randomization. 16,17 …”

“…2,4,5,15 In the ASSERT study with EFV as the third drug among 385 treatment-naive subjects, a significantly lower proportion achieved a viral load of <50 copies/mL at 48 weeks in the ABC/3TC arm (59%) compared to in the TDF/FTC arm (71%). 4 Alternatively, in the HEAT study with lopinavir/ritonavir as the third drug among 688 treatment-naive subjects, ABC/3TC was shown to be non-inferior to TDF/FTC with 68% and 67% of subjects, respectively, achieving a viral load of <50 copies/mL at 48 weeks, with similar outcomes also seen in individuals with a viral load of ≥100,000 copies/mL.…”