Efficacy of the Dapivirine Vaginal Ring Accounting for Imperfect Adherence.

Autor: Husnik MJ; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Heffron R; Department of Epidemiology, University of Washington, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Hughes JP; Department of Biostatistics, University of Washington, Seattle, WA, USA., Richardson B; Department of Biostatistics, University of Washington, Seattle, WA, USA., van der Straten A; Department of Medicine, The Center for AIDS Prevention Studies, University of California San Francisco, San Francisco, CA, USA.; ASTRA Consulting, Kensington, CA, USA., Palanee-Phillips T; Faculty of Health Sciences, Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa., Soto-Torres L; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Singh D; University of Pittsburgh, Pittsburgh, PA, USA.; Magee-Womens Research Institute, Pittsburgh, PA, USA., Mirembe BG; Makerere University John Hopkins University Research Collaboration (MU-JHU), Kampala, Uganda., Livant E; Magee-Womens Research Institute, Pittsburgh, PA, USA., Gaffoor Z; HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa., Mansoor LE; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa., Siva SS; HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa., Dadabhai S; Johns Hopkins Bloomberg School of Public Health, Blantyre, Malawi., Kiweewa FM; Makerere University John Hopkins University Research Collaboration (MU-JHU), Kampala, Uganda., Baeten JM; Department of Epidemiology, University of Washington, Seattle, WA, USA. jbaeten@uw.edu.; Department of Global Health, University of Washington, Seattle, WA, USA. jbaeten@uw.edu.
Jazyk: angličtina
Zdroj: AIDS and behavior [AIDS Behav] 2024 Nov; Vol. 28 (11), pp. 3873-3882. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1007/s10461-024-04463-3
Abstrakt: Product adherence is critical to obtaining objective estimates of efficacy of pre-exposure prophylactic interventions against HIV-1 infection. With imperfect adherence, intention-to-treat analyses assess the collective effects of complete, sub-optimal and non-adherence, providing a biased and attenuated estimate of the average causal effect of an intervention. Using data from the MTN-020/ASPIRE phase III trial evaluating HIV-1 efficacy of the dapivirine vaginal ring, we conducted per-protocol, and adherence-adjusted causal inference analyses using principal stratification and marginal structural models. We constructed two adherence cut offs of ≥ 0.9 mg (low cutoff) and > 4.0 mg (high cutoff) that represent drug released from the ring over a 28-day period. The HIV-1 efficacy estimate (95% CI) was 30.8% (3.6%, 50.3%) (P = 0.03) from the per-protocol analysis, and 53.6% (16.5%, 74.3%) (P = 0.01) among the highest predicted adherers from principal stratification analyses using the low cutoff. Marginal structural models produced efficacy estimates (95% CIs) ranging from 48.8 (21.8, 66.4) (P = 0.0019) to 56.5% (32.8%, 71.9%) (P = 0.0002). Application of adherence-adjusted causal inference methods are useful in interpreting HIV-1 efficacy in secondary analyses of PrEP clinical trials.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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