by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
June 13, 2019
Wohl DA et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: Week 96 results from a randomized, double-blind, multicenter, phase 3, non-inferiority trial.
See also: Stellbrink HJ et al. Lancet HIV. 2019 Jun;6(6): e364-e372.
Fixed dose bictegravir with emtricitabine and tenofovir alafenamide (BIC/TAF/FTC) has become one of the first-line DHHS recommended regimens for HIV treatment-naïve patients. This recommendation is based on 48-week data from several clinical trials with this integrase inhibitor-based regimen. The primary objective of this on-going study is to evaluate the efficacy, safety and tolerability of B/F/TAF versus fixed-dose abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-infected adults. This paper includes the 96-week data from the study, which is being conducted at 122 outpatient sites in nine countries. Enrollees are HIV-infected adults (aged ≥18 years) who were treatment naïve, HLA-B*5701 negative, did not have chronic HBV, and had an estimated GFR of at >50 mL/min. Subjects were randomly assigned (1:1) to receive co-formulated BIC/TAF/FTC or ABC/DTG/3TC. The study included 631 patients of whom half received BIC/TAF/FTC and half were given ABC/DTG/3TC. At week 96, 88% of participants in the in the BIC/TAF/FTC group and 90% in the ABC/DTG/3TC group had HIV-1 RNA < 50 copies/mL. This easily met the pre-specified non-inferiority margin of -12%. The most common adverse events were nausea reported in 11% of the bictegravir group vs 24% for the dolutegravir group, headache 13% vs 16%, and diarrhea 15% vs 16%. There were two deaths in the bictegravir group (one drug overdose and one suicide, neither was treatment related) and no deaths in the dolutegravir group. None of the participants stopped therapy due to adverse events in the bictegravir group compared to five in the dolutegravir group. These data continue to support the use of B/F/TAF in treatment naïve HIV-infected adults.
Commentary: These data confirm the effectiveness, safety, durability as well as the non-inferiority of these two first-line DHHS (A1) regimens. Another Phase 3 trial with a similar design (FTC/TAF was given to all patients) was concurrently published in the same issue of Lancet HIV and at 96 weeks, 84% of bictegravir and 86% of dolutegravir subjects had viral loads < 50 copies/mL. Resistance to bictegravir as well as dolutegravir continues to be extremely rare. More long-term data from this study is forthcoming as it is planned to be to go to at least 144 weeks with an estimated completion data of August 2021.