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Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned.
Antiviral Res. 2013 Sep; 99(3):391-400.AR

Abstract

The development of topically applied products capable of preventing vaginal and rectal transmission of HIV-1 has been on-going for nearly 20 years. Despite this, only one clinical trial has demonstrated protection against sexual transmission of HIV-1 in women. This review covers the development of microbicides, also referred to as topical pre-exposure prophylaxis (PrEP), through three stages. The first stage focused on nonspecific agents, including surfactants such as nonoxynol-9 (N-9), to prevent HIV-1 transmission. Unfortunately, N-9 enhanced susceptibility to sexual transmission of HIV-1 when evaluated for efficacy. Soon thereafter, other nonspecific agents (polyanions) were quickly moved into large efficacy trials. Due to a lack of coordination among investigators and funders, a large investment was made in a class of compounds shown ultimately to be ineffective, although poor adherence may have contributed to these findings. The second stage involved the assessment of the antiretroviral drug tenofovir, formulated as a vaginal gel, which was found to be modestly effective in a Phase IIb trial (CAPRISA-004) when dosed in a coitally-dependent manner. In another Phase IIb trial, VOICE (MTN-003), tenofovir gel was found to be ineffective when dosed once-daily in a coitally-independent manner. Based on pharmacokinetic data, it was concluded the participants were poorly adherent to this dosing regimen, leading to a lack of efficacy. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS-001), using the coitally-dependent dosing regimen employed in CAPRISA-004. We are now in the third stage of microbicide research. The antiretroviral drug dapivirine is currently in two Phase III safety and efficacy studies formulated as a vaginal ring. It is hoped that the once-monthly dosing regimen will lead to higher adherence than found in the VOICE study. It is now clear that product adherence could be the greatest challenge to demonstrating topical (and to a similar extent oral) PrEP. Novel dosage forms should play a role in creating products that women will use correctly.

Authors+Show Affiliations

CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, VA 22209, USA. Electronic address: dfriend@conrad.org.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

23845918

Citation

Friend, David R., and Patrick F. Kiser. "Assessment of Topical Microbicides to Prevent HIV-1 Transmission: Concepts, Testing, Lessons Learned." Antiviral Research, vol. 99, no. 3, 2013, pp. 391-400.
Friend DR, Kiser PF. Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. Antiviral Res. 2013;99(3):391-400.
Friend, D. R., & Kiser, P. F. (2013). Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. Antiviral Research, 99(3), 391-400. https://doi.org/10.1016/j.antiviral.2013.06.021
Friend DR, Kiser PF. Assessment of Topical Microbicides to Prevent HIV-1 Transmission: Concepts, Testing, Lessons Learned. Antiviral Res. 2013;99(3):391-400. PubMed PMID: 23845918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. AU - Friend,David R, AU - Kiser,Patrick F, Y1 - 2013/07/08/ PY - 2013/04/26/received PY - 2013/06/26/revised PY - 2013/06/28/accepted PY - 2013/7/13/entrez PY - 2013/7/13/pubmed PY - 2014/5/3/medline KW - Adherence KW - Intravaginal rings KW - Microbicide KW - Multipurpose prevention technologies KW - Pre-exposure prophylaxis KW - Vaginal gels SP - 391 EP - 400 JF - Antiviral research JO - Antiviral Res VL - 99 IS - 3 N2 - The development of topically applied products capable of preventing vaginal and rectal transmission of HIV-1 has been on-going for nearly 20 years. Despite this, only one clinical trial has demonstrated protection against sexual transmission of HIV-1 in women. This review covers the development of microbicides, also referred to as topical pre-exposure prophylaxis (PrEP), through three stages. The first stage focused on nonspecific agents, including surfactants such as nonoxynol-9 (N-9), to prevent HIV-1 transmission. Unfortunately, N-9 enhanced susceptibility to sexual transmission of HIV-1 when evaluated for efficacy. Soon thereafter, other nonspecific agents (polyanions) were quickly moved into large efficacy trials. Due to a lack of coordination among investigators and funders, a large investment was made in a class of compounds shown ultimately to be ineffective, although poor adherence may have contributed to these findings. The second stage involved the assessment of the antiretroviral drug tenofovir, formulated as a vaginal gel, which was found to be modestly effective in a Phase IIb trial (CAPRISA-004) when dosed in a coitally-dependent manner. In another Phase IIb trial, VOICE (MTN-003), tenofovir gel was found to be ineffective when dosed once-daily in a coitally-independent manner. Based on pharmacokinetic data, it was concluded the participants were poorly adherent to this dosing regimen, leading to a lack of efficacy. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS-001), using the coitally-dependent dosing regimen employed in CAPRISA-004. We are now in the third stage of microbicide research. The antiretroviral drug dapivirine is currently in two Phase III safety and efficacy studies formulated as a vaginal ring. It is hoped that the once-monthly dosing regimen will lead to higher adherence than found in the VOICE study. It is now clear that product adherence could be the greatest challenge to demonstrating topical (and to a similar extent oral) PrEP. Novel dosage forms should play a role in creating products that women will use correctly. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/23845918/Assessment_of_topical_microbicides_to_prevent_HIV_1_transmission:_concepts_testing_lessons_learned_ DB - PRIME DP - Unbound Medicine ER -