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The development of vaginal microbicides for the prevention of HIV transmission.

Weber J, Desai K, Darbyshire J, Microbicides Development Program - PLoS Med. (2005)

View Article: PubMed Central - PubMed

Affiliation: Wright-Fleming Institute, Imperial College London, United Kingdom. j.weber@imperial.ac.uk

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Microbicides are chemical agents used topically by women within the vagina in order to prevent infection by HIV and potentially by other enveloped viruses and sexually transmitted pathogens... Prototype microbicides are designed to be inserted prior to each act of sexual intercourse and could also be contraceptive, although most current potential microbicides are not... N9 has an IC50 of 2–5 ug/ml for both primary and laboratory-adapted HIV-1 strains (IC50 is the quantity of a substance that reduces HIV infection of cells in culture by 50%), and it is active against diverse HIV genotypes in vitro... However, the antiviral effect of N9 is non-specific, with the CC50 (the quantity of a substance required to damage cells in culture such that active uptake of tritiated thymidine or other biomarkers is reduced by 50%) and IC50 occurring at similar concentrations... PRO 2000, carageenan, and cellulose sulphate are all in, or will shortly be in, phase III trials in women at risk of HIV infection in Africa (see Table 1)... There is some evidence that maintenance of this healthy vaginal milieu may protect against infection by HIV and other sexually transmitted infections; all current microbicides are buffered to pH 4.5 in order to promote vaginal health, and all have been investigated for their ability to sustain vaginal lactobacilli in vivo... Adherence to use of the microbicide will be central to a successful outcome, and these agents will need to be used to protect every risky act of intercourse... As with male condoms, adherence is unlikely to be complete, and may reduce over time... Ultimately, it is possible that adherence could be enhanced through novel depot methods for the sustained delivery of microbicides within the vagina without the need for dosing prior to each act of intercourse... Other advocacy groups include the Global Campaign for Microbicides and the Alliance for Microbicides, which ensure that pressure is maintained for funding the development of an effective microbicide... Although it is hoped that one or more of the second-generation potential microbicides will have a positive risk–benefit ratio, they may have only partial efficacy, perhaps being as low as 35% effective... However, modelling suggests that even a microbicide shown to be only partially effective, if used by women in concert with the promotion of condoms for men, would have a beneficial effect on the reduction of HIV transmission at a population level... In a sub-Saharan setting where endemic HIV prevalence is currently 10.8%, the introduction of a microbicide of 50% efficacy covering 50% of sex acts in high-risk women could achieve a population-wide reduction in HIV prevalence to 8.1% after 20 years... Concurrent promotion of condoms additionally covering 50% of sex acts in high-risk men could potentially achieve a prevalence as low as 1.4% (see simulations; Table 2)... In the continued absence of an effective HIV vaccine, a partially active microbicide would still be a highly desirable intervention.

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Sites of Action of Candidate Microbicides(Illustration: Giovanni Maki)
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pmed-0020142-g002: Sites of Action of Candidate Microbicides(Illustration: Giovanni Maki)

Mentions: More recently, the company Biosyn has developed a new surfactant microbicide, SAVVY (Figure 1), which is thought to be significantly less cytotoxic than N9 while retaining antiviral activity, and which is currently in phase III trials in sites in West Africa. SAVVY is believed to exert its virucidal activity through disruption of the HIV envelope lipid bilayer via the same mechanism as N9, although the basis of its lower cytotoxicity is not reported [10].


The development of vaginal microbicides for the prevention of HIV transmission.

Weber J, Desai K, Darbyshire J, Microbicides Development Program - PLoS Med. (2005)

Sites of Action of Candidate Microbicides(Illustration: Giovanni Maki)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1140953&req=5

pmed-0020142-g002: Sites of Action of Candidate Microbicides(Illustration: Giovanni Maki)
Mentions: More recently, the company Biosyn has developed a new surfactant microbicide, SAVVY (Figure 1), which is thought to be significantly less cytotoxic than N9 while retaining antiviral activity, and which is currently in phase III trials in sites in West Africa. SAVVY is believed to exert its virucidal activity through disruption of the HIV envelope lipid bilayer via the same mechanism as N9, although the basis of its lower cytotoxicity is not reported [10].

View Article: PubMed Central - PubMed

Affiliation: Wright-Fleming Institute, Imperial College London, United Kingdom. j.weber@imperial.ac.uk

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Microbicides are chemical agents used topically by women within the vagina in order to prevent infection by HIV and potentially by other enveloped viruses and sexually transmitted pathogens... Prototype microbicides are designed to be inserted prior to each act of sexual intercourse and could also be contraceptive, although most current potential microbicides are not... N9 has an IC50 of 2–5 ug/ml for both primary and laboratory-adapted HIV-1 strains (IC50 is the quantity of a substance that reduces HIV infection of cells in culture by 50%), and it is active against diverse HIV genotypes in vitro... However, the antiviral effect of N9 is non-specific, with the CC50 (the quantity of a substance required to damage cells in culture such that active uptake of tritiated thymidine or other biomarkers is reduced by 50%) and IC50 occurring at similar concentrations... PRO 2000, carageenan, and cellulose sulphate are all in, or will shortly be in, phase III trials in women at risk of HIV infection in Africa (see Table 1)... There is some evidence that maintenance of this healthy vaginal milieu may protect against infection by HIV and other sexually transmitted infections; all current microbicides are buffered to pH 4.5 in order to promote vaginal health, and all have been investigated for their ability to sustain vaginal lactobacilli in vivo... Adherence to use of the microbicide will be central to a successful outcome, and these agents will need to be used to protect every risky act of intercourse... As with male condoms, adherence is unlikely to be complete, and may reduce over time... Ultimately, it is possible that adherence could be enhanced through novel depot methods for the sustained delivery of microbicides within the vagina without the need for dosing prior to each act of intercourse... Other advocacy groups include the Global Campaign for Microbicides and the Alliance for Microbicides, which ensure that pressure is maintained for funding the development of an effective microbicide... Although it is hoped that one or more of the second-generation potential microbicides will have a positive risk–benefit ratio, they may have only partial efficacy, perhaps being as low as 35% effective... However, modelling suggests that even a microbicide shown to be only partially effective, if used by women in concert with the promotion of condoms for men, would have a beneficial effect on the reduction of HIV transmission at a population level... In a sub-Saharan setting where endemic HIV prevalence is currently 10.8%, the introduction of a microbicide of 50% efficacy covering 50% of sex acts in high-risk women could achieve a population-wide reduction in HIV prevalence to 8.1% after 20 years... Concurrent promotion of condoms additionally covering 50% of sex acts in high-risk men could potentially achieve a prevalence as low as 1.4% (see simulations; Table 2)... In the continued absence of an effective HIV vaccine, a partially active microbicide would still be a highly desirable intervention.

Show MeSH