Participation of HIV-1 infected treatment-naive females in clinical trials and sex differences in efficacy and safety outcomes.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
medline:
6
4
2023
pubmed:
3
2
2023
entrez:
2
2
2023
Statut:
ppublish
Résumé
To examine female participation and the observed efficacy and safety by sex from phase 3 HIV-1 trials submitted to the United States Food and Drug Administration (FDA) to support approval or a major labeling change. Our analyses were based on phase 3 trials in HIV-1 infected treatment-naive adults submitted to FDA since 2010. We evaluated enrollment of treatment-naive females in 18 clinical trials for HIV-1. Participation to prevalence ratio (PPR) was calculated as the percentage of females among trial participants divided by the percentage of females in the disease population. PPR between 0.8 and 1.2 reflects similar representation of females in the trial and the disease population. Sex differences in efficacy (virologic response rates) and selected safety events were evaluated. United States (US) females, particularly US Black females were not adequately represented in clinical trials. The PPR for US females overall was 0.59 and for US Black females was 0.63. Statistically significant sex differences favoring males were observed for efficacy outcomes in both the global population and US participants. Statistically significant sex differences were observed for some safety outcomes. US females are underrepresented in phase 3 HIV-1 clinical trials. Underrepresentation was not likely due to enrollment criteria. Statistically significant sex differences were noted for efficacy and selected safety outcomes; however, some differences were not clinically relevant. The ability to detect sex differences was hindered by low numbers of female participants overall and within subgroups. Additional research into innovative approaches to recruit and retain females in clinical trials should continue.
Identifiants
pubmed: 36728423
doi: 10.1097/QAD.0000000000003478
pii: 00002030-202305010-00005
doi:
Substances chimiques
Pharmaceutical Preparations
0
Types de publication
Journal Article
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-903Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
UNAIDS. Fact sheet-world AIDS day 2021. Available at https://www.unaids.org/en/resources/fact-sheet
Diagnoses of HIV Infection in the United States and Dependent Areas, 2019. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/hiv/statistics/overview/ataglance.html
South EM, Zinn RL, Huang CJ, Vasisht KP. US Food and Drug Administration Office of Women's Health: promoting therapeutic optimization in women . J Clin Pharmacol 2020; 60: (Suppl 2): S11–S17.
Mazhude C, Jones S, Murad S, Taylor C, Easterbrook P. Female sex but not ethnicity is a strong predictor of nonnucleoside reverse transcriptase inhibitor-induced rash . AIDS 2002; 16:1566–1568.
Hodder S, Arasteh K, De Wet J, Gathe J, Gold J, Kumar P, et al. Effect of gender and race on the week 48 findings in treatment-naive, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE . HIV Med 2012; 13:406–415.
Sax PE, Erlandson KM, Lake JE, McComsey GA, Orkin C, Esser S, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials . Clin Infect Dis 2020; 71:1379–1389.
Bourgi K, Jenkins CA, Rebeiro PF, Palella F, Moore RD, Altoff KN, et al. Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to nonnucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada . J Int AIDS Soc 2020; 23:e25484.
Kerchberger AM, Sheth AN, Angert CD, Mehta CC, Summers NA, Ofotokun I, et al. Weight gain associated with integrase stand transfer inhibitor use in women . Clin Infect Dis 2020; 71:593–600.
Venter WDF, Sokhela S, Simmons B, Moorhouse M, Fairlie L, Mashabane N, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, noninferiority trial . Lancet HIV 2020; 7:e666–e676.
Soon GG, Min M, Struble KA, Chan-Tack KM, Hammerstrom T, Qi K, et al. Meta-analysis of gender differences in efficacy outcomes for HIV-positive subjects in randomized controlled clinical trials of antiretroviral therapy (2000–2008) . AIDS Patient Care STDS 2012; 26:444–453.
Squires KE, Young B, Santiago L, Dretler RH, Walmsley SL, Zhao HH, et al. Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks . HIV AIDS (Auckl) 2017; 9:51–61.
Squires KE, Johnson M, Yang R, Uy J, Sheppard L, Absalon J, et al. Comparative gender analysis of the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir at 96 weeks in the CASTLE study . J Antimicrob Chemother 2011; 66:363–370.
Nicastri E, Angeletti C, Palmisano L, Sarmati L, Chiesi A, Geraci A, et al. Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy . AIDS 2005; 19:577–583.
Scott PE, Unger EF, Jenkins MR, Southworth MR, McDowell TY, Geller RJ, et al. Participation of women in clinical trials supporting FDA approval of cardiovascular drugs . J Am Coll Cardiol 2018; 71:1960–1969.
Prevention CDC. HIV Surveillance Report, 2018 (Updated); vol.31. May Available at: https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2018-updated-vol-31.pdf
Administration FDA. Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment Guidance for Industry. 2015. Available at https://www.fda.gov/files/drugs/published/Human-Immunodeficiency-Virus-1-Infection--Developing-Antiretroviral-Drugs-for-Treatment.pdf
Hawkins T. Understanding and managing the adverse effects of antiretroviral therapy . Antiviral Res 2010; 85:201–209.
Tracy LA, Struble K, Firnhaber C, Smeaton L, Lake JE, Bell T, et al. Age differences by sex in antiretroviral-naive participants: pooled analysis from randomized clinical trials . J Assoc Nurses AIDS Care 2018; 29:371–382.
U.S. Department of Health and Human Services NIoH, National Institute of Allergy and Infectious Disease. Division of AIDS (DAIDS) Table for grading the severity of adult and pediatric adverse events. 2017. Available at https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables
Prevention CDC. HIV Surveillance Report, 2009; vol. 21. 2011. Available at https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2009-vol-21.pdf
Smeaton LM, Kacanek D, Mykhalchenko K, Coughlin K, Klingman KL, Koletar SL, et al. Screening and enrollment by sex in human immunodeficiency virus clinical trials in the United States . Clin Infect Dis 2020; 71:1300–1305.
Mendez KJW, Cudjoe J, Strohmayer S, Han HR. Recruitment and retention of women living with HIV for clinical research: a review . AIDS Behav 2021; 25:3267–3278.
Grewe ME, Ma Y, Gilbertson A, Rennie S, Tucker JD. Women in HIV cure research: multilevel interventions to improve sex equity in recruitment . J Virus Erad 2016; 2:49–51.
Hall HI, Song R, Tang T, An Q, Prejean J, Dietz P, et al. HIV trends in the United States: diagnoses and estimated incidence . JMIR Public Health Surveill 2017; 3:e8.
Currier J, Averitt Bridge D, Hagins D, Zorrilla CD, Feinberg J, Ryan R, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial . Ann Intern Med 2010; 153:349–357.
Diverse Women in Clinical Trials Campaign U.S. FDA's Office of Women's Health.