Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial
Ivana Beesham, Leila E Mansoor, Dvora L Joseph Davey, Thesla Palanee-Phillips, Jenni Smit, Khatija Ahmed, Pearl Selepe, Cheryl Louw, Mandisa Singata-Madliki, Philip Kotze, Renee Heffron, Urvi M Parikh, Lubbe Wiesner, Helen Rees, Jared M Baeten, Mags Beksinska, Ivana Beesham, Leila E Mansoor, Dvora L Joseph Davey, Thesla Palanee-Phillips, Jenni Smit, Khatija Ahmed, Pearl Selepe, Cheryl Louw, Mandisa Singata-Madliki, Philip Kotze, Renee Heffron, Urvi M Parikh, Lubbe Wiesner, Helen Rees, Jared M Baeten, Mags Beksinska
Abstract
Background: HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.
Methods: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification.
Results: Of 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83-104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83).
Conclusions: Over a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end.
Clinical trial number: NCT02550067.
Conflict of interest statement
The authors have no conflicts of interest to disclose.
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
References
- UNAIDS. Fact Sheet: 2021. Available at: . Accessed July 26, 2021.
- UNAIDS. Country Fact Sheet, South Africa: 2020. Available at: . Accessed July 26, 2021.
- World Health Organization. Guideline on when to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV; 2015. Available at: . Accessed December 9, 2020.
- Medicines Control Council (MCC) & Department of Health, South Africa. Press Release: Medicines Control Council Approves Fixed-Dose Combination of Tenofovir Disoproxyl Fumarate and Emtricitabine for Pre-exposure Prophylaxis of HIV; 2015. Available at: . Accessed July 29, 2021.
- Haberer JE. Current concepts for PrEP adherence in the PrEP revolution: from clinical trials to routine practice. Curr Opin HIV AIDS. 2016;11:10–17.
- Sheth AN, Rolle CP, Gandhi M. HIV pre-exposure prophylaxis for women. J Virus Erad. 2016;2:149–155.
- Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372:509–518.
- Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–422.
- Bekker LG, Roux S, Sebastien E, et al. Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial. Lancet HIV. 2018;5:e68–e78.
- Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial [published correction appears in Lancet. 2019 Jul 27;394(10195):302]. Lancet. 2019;394:303–313.
- Beesham I, Welch JD, Heffron R, et al. Integrating oral PrEP delivery among African women in a large HIV endpoint-driven clinical trial. J Int AIDS Soc. 2020;23:e25491.
- Phillips TK, Sinxadi P, Abrams EJ, et al. A comparison of plasma efavirenz and tenofovir, dried blood spot tenofovir-diphosphate, and self-reported adherence to predict virologic suppression among South African women. J Acquir Immune Defic Syndr. 2019;81:311–318.
- Spinelli MA, Haberer JE, Chai PR, et al. Approaches to objectively measure antiretroviral medication adherence and drive adherence interventions. Curr HIV/AIDS Rep. 2020;17:301–314.
- Hendrix CW, Andrade A, Bumpus NN, et al. Dose frequency ranging pharmacokinetic study of tenofovir-emtricitabine after directly observed dosing in healthy volunteers to establish adherence benchmarks (HPTN 066). AIDS Res Hum Retroviruses. 2016;32:32–43.
- StataCorp. College Station, TX: StataCorp LP. Available at: . Accessed June 30, 2021.
- Celum C, Hosek S, Tsholwana M, et al. PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: results from HPTN 082, a randomized controlled trial. PLoS Med. 2021;18:e1003670.
- Pintye J, Kinuthia J, Abuna F, et al. Frequency and predictors of tenofovir-diphosphate detection among young Kenyan women in a real-world pre-exposure prophylaxis implementation program. Clin Infect Dis. 2020;71:e509–e512.
- Anderson PL, Liu AY, Castillo-Mancilla JR, et al. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrob Agents Chemother. 2017;62:e01710–17.
- AVAC. Defining and Measuring the Effective Use of PrEP: Think Tank Meeting Report. June 18- 19, 2019. Available at: . Accessed July 26, 2021.
- Donnell D, Beesham I, Welch JD, et al. Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study. Lancet HIV. 2021;8:e495–e501.
- Stankevitz K, Grant H, Lloyd J, et al. Oral preexposure prophylaxis continuation, measurement and reporting. AIDS. 2020;34:1801–1811.
Source: PubMed