Achievement of undetectable HIV-1 RNA in the B/F/TAF treatment-naïve clinical trials

BACKGROUND: HIV-1 viral loads (VL) that are <50 c/mL but still detectable may be associated with virologic rebound and elevated inflammatory markers. Studies 1489 and 1490 are phase 3, randomized, double-blind, active-controlled studies of initial HIV-1 treatment which demonstrated that bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) was non-inferior to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and DTG+F/TAF through 144 weeks. Participants' VL were measured using the COBAS^® TaqMan^® v2.0 test, which quantitates HIV RNA from 20 to 10,000,000 c/mL and provides qualitative target detected (TD) or target not detected (TND) results for VL <20 c/mL. Here, we assessed achievement of undetectable HIV-1 RNA (TND) in Studies 1489 and 1490.
METHODS: Participants with at least one on-treatment post-baseline VL value had treatment efficacy assessed by missing=excluded imputation at each study visit using a range of VL endpoints through Week 144. Predictors of consistent TND (TND at '¥85% of visits between Weeks 48 and 144) were studied using a multivariate logistic regression analysis.
RESULTS: At Week 144, 99% of participants in the B/F/TAF, DTG/ABC/3TC, and DTG+F/TAF groups had VL <50 c/mL. The percentages with undetectable VL <20 c/mL TND at Week 144 were lower for all groups: 71% B/F/TAF, 74% DTG/ABC/3TC, and 72% DTG+F/TAF. Achievement of TND at Week 144 was associated with baseline VL '¤100,000 c/mL, baseline CD4 count '¥200 cells/"µL, and adherence by pill count '¥95%. The stringent criteria of '¥85% consistent TND between Weeks 48 and 144 (generally 8-9 of 9 visits) was achieved in 29% to 35% of participants in each treatment group; the pooled participants had a median baseline VL of 11,100 c/mL and CD4 count of 492 cells/"µL. By multivariate logistic regression analysis, consistent TND was associated with baseline VL '¤100,000 c/mL, baseline CD4 count '¥200 cells/"µL, adherence '¥95%, asymptomatic HIV disease, and no secondary INSTI resistance (p<0.05).
CONCLUSIONS: Treatment with B/F/TAF, DTG/ABC/3TC, and DTG+F/TAF achieved similar proportions of VL <20 c/mL TND at all visits through Week 144. Consistent TND was associated with several factors, including lower baseline VL, higher baseline CD4 cell count, and high adherence. These data can be used to design studies with enhanced frequency of TND outcomes, which could aid cure research.