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Tytuł:
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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.
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Autorzy:
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Cahn P; Fundación Huesped, Buenos Aires, Argentina.
Madero JS; Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Arribas JR; Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain.
Antinori A; Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani IRCCS, Rome, Italy.
Ortiz R; Bliss Healthcare Services, Orlando, FL.
Clarke AE; Royal Sussex County Hospital, Brighton, United Kingdom.; Brighton & Sussex Medical School, Brighton, United Kingdom.
Hung CC; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Rockstroh JK; Department of Medicine, Universitätsklinikum Bonn, Bonn, Germany.
Girard PM; Hôpital Saint Antoine, Paris, France.
Sievers J; Research & Development and Global Medical, ViiV Healthcare, Brentford, United Kingdom.
Man CY; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Urbaityte R; Pharma Research & Development, GlaxoSmithKline, Stockley Park, United Kingdom.
Brandon DJ; Pharma Research & Development, GlaxoSmithKline, Stockley Park, United Kingdom.
Underwood M; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Tenorio AR; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Pappa KA; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Wynne B; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Gartland M; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
Aboud M; Research & Development and Global Medical, ViiV Healthcare, Brentford, United Kingdom.
van Wyk J; Research & Development and Global Medical, ViiV Healthcare, Brentford, United Kingdom.
Smith KY; Research & Development and Global Medical, ViiV Healthcare, Research Triangle Park, NC; and.
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Źródło:
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Journal of acquired immune deficiency syndromes (1999) [J Acquir Immune Defic Syndr] 2020 Mar 01; Vol. 83 (3), pp. 310-318.
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Typ publikacji:
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Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Hagerstown, MD : Lippincott Williams & Wilkins, Inc., c1999-
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MeSH Terms:
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HIV-1*
HIV Infections/*drug therapy
Heterocyclic Compounds, 3-Ring/*therapeutic use
Lamivudine/*therapeutic use
Adolescent ; Adult ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Humans ; Lamivudine/administration & dosage ; Male ; Middle Aged ; Oxazines ; Piperazines ; Pyridones ; RNA, Viral/blood ; Young Adult
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References:
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Substance Nomenclature:
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0 (Anti-HIV Agents)
0 (Heterocyclic Compounds, 3-Ring)
0 (Oxazines)
0 (Piperazines)
0 (Pyridones)
0 (RNA, Viral)
2T8Q726O95 (Lamivudine)
DKO1W9H7M1 (dolutegravir)
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Entry Date(s):
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Date Created: 20191214 Date Completed: 20200914 Latest Revision: 20221005
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Update Code:
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20240105
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PubMed Central ID:
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PMC7043729
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DOI:
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10.1097/QAI.0000000000002275
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PMID:
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31834000
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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.
Erratum in: J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):e21. (PMID: 32530908)
