Preplanned subanalysis shows comparable viral suppression rates for two dolutegravir-based regimens in antiretroviral-naive people with HIV at week 48

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AIDS (London, England) Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Cordova Ezequiel, Hernandez Rendon Jenifer, Arevalo Calderon Gisela, Seleme Soledad, Mingrone Veroni… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Viral suppression rates at week 48 were comparable between dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate with emtricitabine or lamivudine in participants with baseline resistance mutations.

This preplanned subanalysis examined a randomized, open-label, phase IV study involving 211 antiretroviral-naive individuals with HIV. The primary objective was to assess the proportion of participants achieving HIV-1 RNA levels below 50 copies per milliliter at week 48 specifically among those with baseline treatment resistance-associated mutations.

The intervention group received dolutegravir plus lamivudine, while the comparator group received dolutegravir plus tenofovir disoproxil fumarate with either emtricitabine or lamivudine. In the modified intent-to-treat analysis, 85.7% of participants in the intervention arm achieved viral suppression compared to 91.7% in the comparator arm. This difference was not statistically significant with a p-value of 0.67.

An observed analysis yielded similar results, showing 96.0% suppression for the intervention group versus 95.7% for the comparator. Additionally, within the intervention arm, suppression rates were 96.0% for those with mutations and 98.6% for those without, a difference that was also not statistically significant. Safety data were not reported in this specific subanalysis.

Study Details

Study typeRct

Sample sizen = 211

EvidenceLevel 2

PublishedJun 2026

PMID41537536

View Original Abstract ↓

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.