Durable Efficacy of Dolutegravir Plus Lamivudine in Antiretroviral Treatment-Naive Adults With HIV-1 Infection: 96-Week Results From the GEMINI-1 and GEMINI-2 Randomized Clinical Trials
Journal
Journal of acquired immune deficiency syndromes (1999)
Journal Volume
83
Journal Issue
3
Pages
310-318
Date Issued
2020
Author(s)
Cahn P.
Madero J.S.
Arribas J.R.
Antinori A.
Ortiz R.
Clarke A.E.
Rockstroh J.K.
Girard P.-M.
Sievers J.
Man C.Y.
Urbaityte R.
Brandon D.J.
Underwood M.
Tenorio A.R.
Pappa K.A.
Wynne B.
Gartland M.
Aboud M.
van Wyk J.
Smith K.Y.
Abstract
BACKGROUND: The 2-drug regimen dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL in treatment-naive adults in the 48-week primary analysis of the GEMINI trials. We present results from the prespecified 96-week secondary analyses. SETTING: One hundred eighty-seven centers in 21 countries. METHODS: GEMINI-1 and GEMINI-2 are identical, double-blind phase III studies. Participants with screening HIV-1 RNA ?500,000 copies/mL were randomized 1:1 to once-daily dolutegravir + lamivudine or dolutegravir + tenofovir disoproxil fumarate/emtricitabine. RESULTS: At week 96, dolutegravir + lamivudine (N = 716) was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine (N = 717) in achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm; -10% noninferiority margin) in the pooled analysis (proportion of responders, 86.0% vs 89.5%, respectively; adjusted treatment difference [95% CI], -3.4% [-6.7 to 0.0007]), GEMINI-1 (-4.9% [-9.8 to 0.03]), and GEMINI-2 (-1.8% [-6.4 to 2.7]). Proportions of participants in the HIV-1 RNA ?50 copies/mL Snapshot category were largely unchanged from week 48 to 96. Eleven participants taking dolutegravir + lamivudine and 7 taking dolutegravir + tenofovir disoproxil fumarate/emtricitabine met confirmed virologic withdrawal criteria through week 96; none had treatment-emergent resistance mutations. Dolutegravir + lamivudine had a lower rate of drug-related adverse events than dolutegravir + tenofovir disoproxil fumarate/emtricitabine (19.6% vs 25.0%; relative risk ratio, 0.78; 95% CI: 0.64 to 0.95). Renal and bone biomarker changes favored dolutegravir + lamivudine. CONCLUSIONS: Consistent with 48-week data, dolutegravir + lamivudine demonstrated long-term, noninferior efficacy vs dolutegravir + tenofovir disoproxil fumarate/emtricitabine without increased risk of treatment-emergent resistance, supporting its use in treatment-naive HIV-1-infected individuals.
SDGs
Other Subjects
anti human immunodeficiency virus agent; dolutegravir; fused heterocyclic rings; lamivudine; virus RNA; adolescent; adult; blood; combination drug therapy; controlled study; double blind procedure; female; human; Human immunodeficiency virus 1; Human immunodeficiency virus infection; male; middle aged; randomized controlled trial; young adult; Adolescent; Adult; Anti-HIV Agents; Double-Blind Method; Drug Therapy, Combination; Female; Heterocyclic Compounds, 3-Ring; HIV Infections; HIV-1; Humans; Lamivudine; Male; Middle Aged; RNA, Viral; Young Adult
Publisher
NLM (Medline)
Type
journal article