Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial.

Autor:	Chinula L; University of North Carolina Project-Malawi, Lilongwe, Malawi; Division of Global Women's Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: lameck_chinula@med.unc.edu., Ziemba L; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA., Brummel S; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA., McCarthy K; FHI 360, Durham, NC, USA., Coletti A; FHI 360, Durham, NC, USA., Krotje C; Frontier Science & Technology Research Foundation, Amherst, NY, USA., Johnston B; Frontier Science & Technology Research Foundation, Amherst, NY, USA., Knowles K; Frontier Science & Technology Research Foundation, Amherst, NY, USA., Moyo S; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Stranix-Chibanda L; College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe., Hoffman R; University of California Los Angeles, Los Angeles, CA, USA., Sax PE; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Stringer J; Division of Global Women's Health, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Chakhtoura N; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA., Jean-Philippe P; National Institute of Allergy and Infectious Diseases, Rockville, MD, USA., Korutaro V; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda., Cassim H; Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa., Fairlie L; Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa., Masheto G; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Boyce C; Seattle Children's Research Center and University of Washington, Seattle, WA, USA., Frenkel LM; Seattle Children's Research Center and University of Washington, Seattle, WA, USA., Amico KR; Department of Health Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Purdue L; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA., Shapiro R; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Mmbaga BT; Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania., Patel F; Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa., van Wyk J; ViiV Healthcare, Brentford, UK., Rooney JF; Gilead Sciences, Foster City, CA, USA., Currier JS; University of California Los Angeles, Los Angeles, CA, USA., Lockman S; Department of Immunology and Infectious Diseases and Center for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Jazyk:	angličtina
Zdroj:	The lancet. HIV [Lancet HIV] 2023 Jun; Vol. 10 (6), pp. e363-e374. Date of Electronic Publication: 2023 May 08.
DOI:	10.1016/S2352-3018(23)00061-9
Abstrakt:	Background: Drugs taken during pregnancy can affect maternal and child health outcomes, but few studies have compared the safety and virological efficacy of different antiretroviral therapy (ART) regimens. We report the primary safety outcomes from enrolment up to 50 weeks post partum and a secondary virological efficacy outcome at 50 weeks post partum of three commonly used ART regimens for HIV-1. Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, we enrolled pregnant women aged 18 years or older with confirmed HIV-1 infection at 14-28 weeks of gestation. Women were enrolled at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Participants were randomly assigned (1:1:1) to one of three oral regimens: dolutegravir, emtricitabine, and tenofovir alafenamide; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; or efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Up to 14 days of antepartum ART before enrolment was permitted. Women with known multiple gestation, fetal anomalies, acute significant illness, transaminases more than 2·5 times the upper limit of normal, or estimated creatinine clearance of less than 60 mL/min were excluded. Primary safety analyses were pairwise comparisons between ART regimens of the proportion of maternal and infant adverse events of grade 3 or higher up to 50 weeks post partum. Secondary efficacy analyses at 50 weeks post partum included a comparison of the proportion of women with plasma HIV-1 RNA of less than 200 copies per mL in the combined dolutegravir-containing groups versus the efavirenz-containing group. Analyses were done in the intention-to-treat population, which included all randomly assigned participants with available data. This trial was registered with ClinicalTrials.gov, NCT03048422. Findings: Between Jan 19, 2018, and Feb 8, 2019, we randomly assigned 643 pregnant women to the dolutegravir, emtricitabine, and tenofovir alafenamide group (n=217), the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (n=215), and the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (n=211). At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), median CD4 count was 466 cells per μL (308-624), and median HIV-1 RNA was 903 copies per mL (152-5183). 607 (94%) women and 566 (92%) of 617 liveborn infants completed the study. Up to the week 50 post-partum visit, the estimated probability of experiencing an adverse event of grade 3 or higher was 25% in the dolutegravir, emtricitabine, and tenofovir alafenamide group; 31% in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group; and 28% in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (no significant difference between groups). Among infants, the estimated probability of experiencing at least one adverse event of grade 3 or higher by postnatal week 50 was 28% overall, with small and non-statistically significant differences between groups. By postnatal week 50, 14 infants whose mothers were in the efavirenz-containing group (7%) died, compared with six in the combined dolutegravir groups (1%). 573 (89%) women had HIV-1 RNA data available at 50 weeks post partum: 366 (96%) in the dolutegravir-containing groups and 186 (96%) in the efavirenz-containing group had HIV-1 RNA less than 200 copies per mL, with no significant difference between groups. Interpretation: Safety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy. Funding: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health. Competing Interests: Declaration of interests JvW is an employee of ViiV Healthcare and JFR is an employee of Gilead Sciences. All other authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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