Switching treatment-experienced, integrase inhibitor-naïve, virally suppressed HIV-1 infected adults from ritonavir-boosted protease inhibitors to dolutegravir: design, methods, and baseline results of a randomized, open-label, non-inferiority trial

Abstract

Background: Most HIV-positive adults in Kenya with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) failure are currently on ritonavir-boosted protease inhibitors (PI/r). Dolutegravir (DTG) has shown good efficacy among treatment-experienced adults. Objective: Our study is the first to evaluate the efficacy of switching from ritonavir-boosted protease inhibitor (PI/r) to DTG among virally suppressed adults with prior NNRTI failure and with no knowledge of susceptibility to nucleoside reverse transcriptase inhibitors (NRTIs). Methods: This open-label, randomized, active-controlled, non-inferiority trial was conducted at four sites in Kenya. Virally suppressed HIV-1 positive adults (≥ 18 years) on a second-line regimen of PI/r and 2 NRTIs were randomized (1:1) to switch to DTG or continue their pre-enrollment PI/r. The primary endpoint is proportion of participants with HIV-1 RNA ≥ 50 copies/mL at week 48 with a 4% non-inferiority margin. ClinicalTrials.gov registration: NCT04229290. Results: Between Feb 10 and Sep 3, 2020, 1,114 adults were screened, 795 were randomized and 791 treated (397 DTG, 394 baseline PI/r). All participants were black, 66.3% were female, median age was 46 years, and median CD4 count was 423 cells/μl. Grade 2 or higher laboratory abnormalities at baseline included 44.6% with reduced creatinine clearance and 9.7% with elevated lipids. Conclusions: This is the first randomized trial evaluating a switch strategy from PI/r to DTG for virally suppressed adults who have previously failed NNRTI, and is expected to provide critical evidence to inform large HIV programs in sub-Saharan Africa. We found high rates of baseline laboratory abnormalities that were not detected during routine care.