Effectiveness of vaginal microbicides in preventing HIV transmission

Vaginal microbicides for the prevention of HIV transmission maybe an important option for protecting women from infection.Incorporation of dapivirine, a lead candidate nonnucleoside reversetranscriptase inhibitor, into intravaginal rings (IVRs) for sustainedmucosal delivery may increase microbicide product adherence andefficacy compared with conventional vaginal formulations. Twentyfourhealthy HIV-negative women 18–35 years of age were randomlyassigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR,or placebo IVR. Dapivirine concentrations were measured in plasmaand vaginal fluid samples collected at sequential time points over the33-day study period (28 days of IVR use, 5 days of follow-up). Safetywas assessed by pelvic/colposcopic examinations, clinical laboratorytests, and adverse events. Both IVR types were safe and well toleratedwith similar adverse events observed in the placebo and dapivirinegroups. Dapivirine from both IVR types was successfully distributedthroughout the lower genital tract at concentrations over 4 logs greaterthan the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximumconcentration (Cmax) and area under the concentration–time curve(AUC) values were significantly higher with the matrix than reservoirIVR. Mean plasma concentrations of dapivirine were ,2 ng/mL.These findings suggest that IVR delivery of microbicides is a viableoption meriting further study.Key Words: dapivirine, HIV, intravaginal ring, microbicide,pharmacokinetics, prevention

Vaginal Microbicides for the Prevention of HIV Transmission

Biotechnology and Genetic Engineering Reviews ◽

10.1080/02648725.2004.10648050 ◽

2004 ◽

Vol 21 (1) ◽

pp. 81-122 ◽

Cited By ~ 11

Author(s):

Karl Malcolm ◽

David Woolfson ◽

Clare Toner ◽

Deborah Lowry

Keyword(s):

Hiv Transmission ◽

Vaginal Microbicides ◽

Prevention Of Hiv

Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial a mixed-methods study,

10.31234/osf.io/6yafd ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Clinical Trials ◽

Phase I ◽

Phase I Trial ◽

Hiv Transmission ◽

Sexual Transmission ◽

Initial Product ◽

Vaginal Microbicides ◽

Tenofovir Gel ◽

Gender Based ◽

Sexual Transmission Of Hiv

THE GLOBAL HIV EPIDEMIC increasingly affectswomen.1 For most, the only risk factor for becominginfected is the behavior of their male sexualpartners.1 Condoms often are unacceptableand insufficiently used,2–4 gender-based powerimbalances can make them difficult to negotiate,4–7 and religious beliefs, fertility needs, fear ofimplied infidelity, and preferences for sex withouta barrier are challenges to their acceptabilityand use. Women-initiated HIV prevention methodsare urgently needed, making the developmentof vaginal microbicides that reduce the likelihoodof sexual transmission of HIV a majorpublic health priority.First-generation vaginal microbicides will mostlikely be topical gels inserted into the vagina withan applicator. A variety of microbicides is currentlyunder development, and six have enteredlate-stage clinical trials.8–12 Initial product acceptabilityhas been assessed in clinical trials,13–16 surveysof product attributes among potentialusers17,18 and their partners,19 and studies that useover-the-counter (OTC) surrogates or placebo gelwith presumed similar formulation and applicationcharacteristics as eventual products.20–23 Acceptabilityassessments in early clinical trials areespecially important because their findings can influencefurther development of the product.Here, we report on acceptability data amongwomen participating in a phase I trial of tenofovirgel, a candidate microbicide that inhibits HIV reversetranscriptase. Details of the trial are reportedelsewhere,24 as is acceptability amongmale partners of trial participants.25 This was thefirst human trial of a topical antiretroviral thatspecifically inhibits a necessary replication stepin the HIV life cycle. Interest in this approach toHIV prevention has increased in recent yearssince efficacy trials of a topical surfactant(nonoxynyl-9) and a nonspecific inhibitor of HIVbinding (cellulose sulfate) indicated that thesetwo types of compounds were not protective andpotentially increased HIV transmission in womenwho had frequent sexual exposures to HIV. Severallarger-scale, expanded safety and proof-ofconcepttrials of tenofovir gel are now underway,based in part on the safety, tolerability, and acceptabilityof this microbicide demonstrated inthe study described in this paper.

Modeling the gender-specific impact of vaginal microbicides on HIV transmission

Journal of Theoretical Biology ◽

10.1016/j.jtbi.2011.08.001 ◽

2011 ◽

Vol 288 ◽

pp. 9-20 ◽

Cited By ~ 13

Author(s):

Dobromir T. Dimitrov ◽

Marie-Claude Boily ◽

Rebecca F. Baggaley ◽

Benoit Masse

Keyword(s):

Hiv Transmission ◽

Vaginal Microbicides ◽

Gender Specific ◽

Specific Impact

Vaginal microbicides and the prevention of HIV transmission

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(08)70254-8 ◽

2008 ◽

Vol 8 (11) ◽

pp. 685-697 ◽

Cited By ~ 111

Author(s):

Blayne Cutler ◽

Jessica Justman

Keyword(s):

Hiv Transmission ◽

Vaginal Microbicides ◽

Prevention Of Hiv

Development of Preclinical Biomarkers Predictive of Safety of Vaginal Microbicides for the Prevention of HIV

Einstein Journal of Biology and Medicine ◽

10.23861/ejbm20112732 ◽

2016 ◽

Vol 27 (1) ◽

pp. 13

Author(s):

Mohak Mhatre

Keyword(s):

Hiv Transmission ◽

Effective Strategy ◽

Efficacy And Safety ◽

Vaginal Microbicides ◽

Safety Testing ◽

Sexually Transmitted ◽

Immunodeficiency Virus ◽

Topical Microbicides ◽

Microbicide Development ◽

Prevention Of Hiv

Human immunodeficiency virus (HIV) is transmitted predominantly through sexual intercourse. Research suggeststhat the vaginal epithelium acts as a barrier to HIV transmission, but this epithelium can be disrupted, leading toHIV infection and other sexually transmitted infections. Topical microbicides are considered an effective strategy forHIV prevention, and several candidate drugs are currently in clinical trials. However, significant concerns about drugadherence, efficacy, and safety must be addressed in order to develop a safe and effective microbicide. This paper willprovide an overview of the field and strategies to overcome some of the obstacles facing microbicide development,and briefly discuss a research project that focused on one aspect of preclinical microbicide safety testing.

The Development of Vaginal Microbicides for the Prevention of HIV Transmission

PLoS Medicine ◽

10.1371/journal.pmed.0020142 ◽

2005 ◽

Vol 2 (5) ◽

pp. e142 ◽

Cited By ~ 48

Author(s):

Jonathan Weber ◽

Kamal Desai ◽

Janet Darbyshire ◽

Keyword(s):

Hiv Transmission ◽

Vaginal Microbicides ◽

Prevention Of Hiv

HIV/AIDS surveillance and prevention: improving the characterization of HIV transmission

Public Health Reports ◽

10.1016/s0033-3549(04)50240-6 ◽

2003 ◽

Vol 118 (3) ◽

pp. 197-204 ◽

Cited By ~ 5

Author(s):

Mark A Schmidt ◽

Eve D Mokotoff

Keyword(s):

Hiv Transmission ◽

Hiv Aids

Herpes Treatment May Help Prevent HIV Transmission

Internal Medicine News ◽

10.1016/s1097-8690(07)70351-7 ◽

2007 ◽

Vol 40 (7) ◽

pp. 35

Author(s):

TIMOTHY F. KIRN

Keyword(s):

Hiv Transmission

25-jährige Medizinische Praxisassistentin, HIV-Postexpositionsprophylaxe (PEP) nach akzidenteller Nadelstichverletzung

Praxis ◽

10.1024/0369-8394.91.5.184 ◽

2002 ◽

Vol 91 (5) ◽

pp. 184-187

Author(s):

Meienberg

Keyword(s):

Hiv Transmission

Eine 25-jährige Medizinische Praxisassistentin sticht sich an einer HIV-kontaminierten Hohlnadel. Das Risiko einer HIV-Transmission, Indikationen und Nutzen einer Postexpositionsprophylaxe (PEP) werden anhand von einigen Fragen besprochen.