Abstract
BACKGROUND: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART. OBJECTIVES: We report long-term virologic outcomes from a clinical trial. METHOD: AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA ≥ 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one (n = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two (n = 130). We present results up to 158 weeks, combining stages one and two. RESULTS: We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score ≥ 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA < 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA < 50 copies/mL, 11% had HIV-1 RNA 50-999 copies/mL, and 11% had HIV-1 RNA ≥ 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146. CONCLUSION: Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2-3 years on second-line TLD.