Impact of treatment adherence on efficacy of dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine: pooled analysis of the GEMINI-1 and GEMINI-2 clinical studies.

Abstract

Background: GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL at 48, 96, and 144 weeks in treatment-naive adults with HIV-1 infection.Objective: We present a post hoc analysis of the impact of treatment adherence on Week 48 virologic response.Methods: Adherence was estimated using pill counts and categorized as ≥90% vs <90%. Unadjusted treatment differences with exact 95% CIs were derived for the proportion of participants with HIV-1 RNA <50 copies/mL within each adherence category, using Snapshot algorithm and last available on-treatment viral load through Week 48.Results: In each treatment group, 5% of participants had <90% adherence (dolutegravir + lamivudine group, 35/716; dolutegravir + tenofovir disoproxil fumarate/emtricitabine group, 34/717). The proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot) at Week 48 in the <90% adherence group was 69% in the dolutegravir + lamivudine group and 65% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group (analysis by last on-treatment viral load: 91% and 85%, respectively). Corresponding proportions in the ≥90% adherence group were 93% and 96% (analysis by last on-treatment viral load: 97% and 99%, respectively).Conclusions: Decreased adherence resulted in lower Week 48 virologic efficacy outcomes that were comparable between treatment groups. These results indicate that the robust antiviral activity and regimen forgiveness of dolutegravir + lamivudine is similar to dolutegravir-containing 3-drug regimens (see graphical abstract).

• Authors: Mounir Ait-Khaled, Juan Sierra Madero, Vicente Estrada, Roberto Gulminetti, Debbie Hagins, Hung-Chin Tsai, Choy Man, Jörg Sievers, Richard Grove, Andrew Zolopa, Brian Wynne, Jean van Wyk
• Journal: HIV research & clinical practice (HIV Res Clin Pract) Vol. 23 Issue 1 Pg. 9-14 (12 09 2021) ISSN: 2578-7470 [Electronic] England
• PMID: 34913844 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Heterocyclic Compounds, 3-Ring
• Oxazines
• Piperazines
• Pyridones
• Lamivudine
• RNA
• Tenofovir
• dolutegravir
• Emtricitabine

Topics

• Adult
• Anti-HIV Agents (therapeutic use)
• Drug Therapy, Combination
• Emtricitabine
• HIV Infections (drug therapy)
• HIV-1
• Heterocyclic Compounds, 3-Ring
• Humans
• Lamivudine (therapeutic use)
• Oxazines
• Piperazines
• Pyridones
• RNA (therapeutic use)
• Tenofovir
• Treatment Adherence and Compliance