AIDS (London, England) · 2026
Efficacy of dolutegravir plus lamivudine in treatment-naïve people with HIV with baseline transmitted drug-resistance mutations.
СтатьяРандомизированное исследованиеКлиническое исследование IV фазыНазвание и аннотация: Перевод в очереди
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Cordova Ezequiel, Hernandez Rendon Jenifer, Arevalo Calderon Gisela, Seleme Soledad, Mingrone Veronica, Porteiro Norma
Аннотация
BACKGROUND: Dolutegravir plus lamivudine (DTG+3TC) is a recommended first-line regimen for people with HIV (PWH), based on its efficacy and safety. However, pivotal trials excluded individuals with transmitted resistance-associated mutations (tRAMs), even when these did not affect regimen activity. The impact of such mutations on DTG+3TC efficacy remains unknown.
METHODS: This was a preplanned subanalysis of the D2ARLING trial, a randomized, open-label, phase IV study comparing DTG+3TC vs. DTG+tenofovir disoproxil fumarate with emtricitabine or lamivudine (DTG+TDF/XTC) in antiretroviral-naïve PWH without baseline resistance test results. Per protocol, baseline genotypic resistance testing was performed on day 1 but remained blinded throughout the study and was only unblinded after completion. Participants with successfully amplified samples were included. The primary endpoint was the proportion with HIV-1 RNA <50 copies/ml at week 48 among those with baseline tRAMs, using both mITT-exposed and observed analyses.
RESULTS: Among 211 participants (DTG+3TC: 104; DTG+TDF/XTC: 107), tRAMs were detected in 24.6%, mainly nonnucleoside reverse transcriptase inhibitors tRAMs. At week 48, viral suppression among participants with tRAMs was achieved in 85.7% (24/28) with DTG+3TC and 91.7% (22/24) with DTG+TDF/XTC ( P = 0.67; mITT). In the observed analysis, suppression rates were 96.0% and 95.7%, respectively. Within the DTG+3TC arm, week-48 suppression was 96.0% in participants in whom tRAMs were detected and 98.6% in those without detected tRAMs ( P = 0.45). No protocol-defined virological failures occurred in participants with tRAMs receiving DTG+3TC.
CONCLUSIONS: :DTG/3TC showed high efficacy in participants with tRAMs not affecting this regimen. The detection of such tRAMs did not compromise treatment outcomes in treatment-naïve individuals in this setting.
METHODS: This was a preplanned subanalysis of the D2ARLING trial, a randomized, open-label, phase IV study comparing DTG+3TC vs. DTG+tenofovir disoproxil fumarate with emtricitabine or lamivudine (DTG+TDF/XTC) in antiretroviral-naïve PWH without baseline resistance test results. Per protocol, baseline genotypic resistance testing was performed on day 1 but remained blinded throughout the study and was only unblinded after completion. Participants with successfully amplified samples were included. The primary endpoint was the proportion with HIV-1 RNA <50 copies/ml at week 48 among those with baseline tRAMs, using both mITT-exposed and observed analyses.
RESULTS: Among 211 participants (DTG+3TC: 104; DTG+TDF/XTC: 107), tRAMs were detected in 24.6%, mainly nonnucleoside reverse transcriptase inhibitors tRAMs. At week 48, viral suppression among participants with tRAMs was achieved in 85.7% (24/28) with DTG+3TC and 91.7% (22/24) with DTG+TDF/XTC ( P = 0.67; mITT). In the observed analysis, suppression rates were 96.0% and 95.7%, respectively. Within the DTG+3TC arm, week-48 suppression was 96.0% in participants in whom tRAMs were detected and 98.6% in those without detected tRAMs ( P = 0.45). No protocol-defined virological failures occurred in participants with tRAMs receiving DTG+3TC.
CONCLUSIONS: :DTG/3TC showed high efficacy in participants with tRAMs not affecting this regimen. The detection of such tRAMs did not compromise treatment outcomes in treatment-naïve individuals in this setting.