Bictegravir, emtricitabine, and tenofovir alafenamide versus ritonavir-boosted protease inhibitor-based antiretroviral therapy in people with HIV and viral suppression on second-line therapy in Haiti: an open-label, randomised, non-inferiority trial

Abstract

Background: Patients on second-line protease inhibitor-based regimens in low-income and middle-income countries have high rates of nucleoside reverse transcriptase inhibitor (NRTI) resistance, but access to testing is scarce. We aimed to assess the efficacy of combination oral bictegravir, emtricitabine, and tenofovir alafenamide in this population.

Methods: In this open-label non-inferiority trial conducted in Port-au-Prince, Haiti, adults (aged 18 years or older) with viral suppression (HIV-1 RNA <200 copies per mL) on second-line regimens including ritonavir-boosted protease inhibitors and two NRTIs were randomised (1:1) using a computer-generated random-number list. Participants either switched from their current regimen to combination oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily (bictegravir group) or continued their current regimen (atazanavir 300 mg and ritonavir 100 mg once daily or lopinavir 400 mg and ritonavir 100 mg twice daily plus two NRTIs; boosted protease inhibitor group). The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 200 copies or more per mL at week 48, in accordance with the US Food and Drug Administration Snapshot algorithm. Primary and safety analyses were conducted in the intention-to-treat population, which included all participants who underwent randomisation and received at least one dose of study medication. The prespecified non-inferiority margin was 4%. The study is registered with ClinicalTrials.gov (NCT04311957).

Findings: Between Oct 23, 2020, and April 21, 2023, 444 people with HIV were screened for eligibility and 301 were randomly assigned to the bictegravir group (n=153) or to the boosted protease inhibitor group (n=148). The median age at enrolment was 49·5 years (IQR 43·6-56·2) in the bictegravir group and 48·0 (40·5-57·4) years in the boosted protease inhibitor group. 173 (57%) participants were women and 128 (43%) were men. All participants were Black. Enrolment was stopped early due to restricted access to the protease inhibitor-based regimen. At week 48, the proportion of participants with HIV-1 RNA of 200 copies per mL or more was 0·7% (one of 153 participants) in the bictegravir group and 4·1% (six of 148 participants) in the boosted protease inhibitor group (difference -3·4%, 95% CI -8·1 to 0·2), meeting non-inferiority criteria. Four participants in each group developed a new grade 3 or 4 adverse event, but no study drug was discontinued due to adverse events.

Interpretation: Switching adults with HIV and viral suppression on a second-line boosted protease inhibitor-based regimen to combination bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to continuing boosted protease inhibitor-based antiretroviral therapy. These findings support international treatment guideline recommendations to use second-generation integrase inhibitors for treatment-experienced patients.

Funding: Gilead Sciences.

Translation: For the French translation of the abstract see Supplementary Materials section.