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Population Effectiveness of Dolutegravir Implementation in Uganda: A Prospective Observational Cohort Study (DISCO), 48-Week Results

Suzanne M. McCluskey, Winnie Muyindike, Victoria Nanfuka, Daniel Omoding, Nimusiima Komukama, Ian T. Barigye, Lydia Kansiime, Justus Tumusiime, Taing N. Aung, Ashley Stuckwisch, Bethany Hedt‐Gauthier, Vincent C. Marconi, Mahomed‐Yunus S. Moosa, Deenan Pillay, Jennifer Giandhari, Richard Lessells, Ravindra K. Gupta, Mark J. Siedner

2024The Journal of Infectious Diseases13 citationsDOIOpen Access PDF

Abstract

BACKGROUND: Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on nonnucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics. METHODS: We conducted a prospective cohort study of PWH aged ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24 and 48 weeks later. The primary end point was viral suppression (<200 copies/mL) at 48 weeks. We collected blood for retrospective viral load (VL) assessment and conducted genotypic resistance tests for specimens with VL >500 copies/mL. RESULTS: We enrolled 500 participants (median age 47 years; 41% women). At 48 weeks after TLD transition, 94% of participants were in care with a VL <200 copies/mL (n = 469/500); 2% (n = 11/500) were lost from care or died; and only 2% (n = 9/500) had a VL >500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events. CONCLUSIONS: High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region. CLINICAL TRIALS REGISTRATION: NCT04066036.

Topics & Concepts

RegimenMedicineDolutegravirTolerabilityLamivudineInternal medicineAdverse effectViral loadProspective cohort studyPopulationCohort studyAntiretroviral therapyVirologyHuman immunodeficiency virus (HIV)VirusEnvironmental healthHepatitis B virusHIV/AIDS drug development and treatmentHIV/AIDS Research and InterventionsHIV-related health complications and treatments