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{{Short description|Pharmacologic agents and chemical substances}}
{{Copy edit|for=spelling, grammar and organization|date=October 2010}}
'''Microbicides for ]s''' are ] agents and ]s that are capable of killing or destroying certain ]s that commonly cause sexually transmitted infection (for example, the ]).

{{drugbox
| verifiedrevid = 414574552
| IUPAC_name ={(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid
| image =Tenofovir.svg
| alt =Tenofovir disoproxil fumarate
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| CAS_number =147127-20-6
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| C=9|H=14|N=5|O=4|P=1
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| pregnancy_category = B ( U.S. )
| legal_status =℞-only (U.S.) , POM ( UK )
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}}

{{See also|Antiseptics}}
'''Microbicides''' for ]s, are ] agents and ]s that are capable of killing or destroying certain ]s that commonly cause human ], for example the ].


Microbicides are a diverse group of ]s that exert their activity by a variety of different ]. Microbicides are a diverse group of ]s that exert their activity by a variety of different ].
Multiple compounds are being developed and tested for their microbicidal activity in ]s. Microbicides can be formulated in various ] including ]s, ], ]s, ]s, ] or ] (which must be used near the time of ]) and sponges and ]s (or other devices that release the ](s) over a longer period). Some of these agents are being developed for ]l application, and for ] use by those engaging in ].{{citation needed|date=September 2023}}


Although there are many approaches to preventing sexually transmitted infections in general (and HIV in particular), current methods have not been sufficient to halt the spread of these infections (particularly among women and people in ]). ] is not a realistic option for women who want to bear children, or who are at risk of ].<ref>{{Cite web
Multiple compounds are currently being developed and tested for their microbicidal activity in ]s. Microbicides can be formulated in various ], including ]s, ], ]s, ]s, ]s or ] that must be used near the time of ], or as sponges, ]s or other devices that release the ](s) over a longer period of time. Some of these agents are being developed for ]l application, for ] use by those who engage in ].
| last = gender

| title = Research: hiv aids
Although there are many approaches to preventing sexually transmitted diseases in general and HIV in particular, current methods have not been sufficient to halt the spread of these diseases — particularly among women and people who live in ]. ] is not a realistic option for women who want to bear children or who are at risk of ].<ref>{{Cite web
| url=https://www.who.int/gender/hiv_aids/en/index.html
| last = gender
| archive-url=https://web.archive.org/web/20040529135422/http://www.who.int/gender/hiv_aids/en/index.html
| first =
| url-status=dead
| title = Research: hiv aids
| archive-date=May 29, 2004
| url=http://www.who.int/gender/hiv_aids/en/index.html
| access-date = 1 April 2018
| accessdate = october 2010
}}</ref> In such situations, use of microbicides could offer both primary protection in the absence of ]s and secondary protection if a condom breaks or slips off during intercourse. Microbicides may eventually prove to be safe and effective in reducing the risk of HIV ] during ] with an infected partner.<ref>{{Cite web }}</ref> In such situations, the use of microbicides could offer both primary protection (in the absence of ]s) and secondary protection (if a condom breaks or slips off during intercourse). It is hoped that microbicides may be safe and effective in reducing the risk of HIV ] during ] with an infected partner.<ref>{{Cite web
| last = global-campaign | last = global-campaign
| title = Research: microbicides
| first =
| url=http://www.global-campaign.org/about_microbicides.htm
| title = Research: microbicides
| access-date = 1 April 2018
| url=http://www.global-campaign.org/about_microbicides.htm
| accessdate = october 2010
}}</ref><ref>{{Cite web }}</ref><ref>{{Cite web
| last = rectalmicrobicide | last = rectalmicrobicide
| title = Research: rectalmicrobicides
| first =
| title = Research: rectalmicrobicides | url = http://www.rectalmicrobicides.org/
| access-date = 1 April 2018
| url=http://www.rectalmicrobicides.org/
| archive-date = 30 October 2020
| accessdate = october 2010
| archive-url = https://web.archive.org/web/20201030053649/https://rectalmicrobicides.org/
}}</ref>
| url-status = dead
}}</ref>{{Full citation needed|date=December 2011}}


==Mechanisms of action== ==Mechanisms of action==

=== Detergents === === Detergents ===
] and ] microbicides such as ], ] and Savvy (1.0% C31G), act by disrupting the ], ] or ] of microorganisms. Since detergent microbicides also kill host cells and impair the barrier function of healthy ] surfaces, they are less desirable than other agents. Additionally, clinical trials have not demonstrated these agents to be effective at preventing HIV transmission.{{Citation needed|date=October 2010}} Consequently, laboratory and clinical trials testing this class of products as microbicides have largely been discontinued.<ref>{{cite journal | vauthors = Lederman MM, Offord RE, Hartley O | title = Microbicides and other topical strategies to prevent vaginal transmission of HIV | journal = Nature Reviews. Immunology | volume = 6 | issue = 5 | pages = 371–82 | date = May 2006 | pmid = 16639430 | doi = 10.1038/nri1848 | s2cid = 28270072 | url = http://files.chuv.ch/internet-docs/ial/ial_lederman_etal_06.pdf | access-date = 2013-03-22 | archive-date = 2015-07-01 | archive-url = https://web.archive.org/web/20150701011353/http://files.chuv.ch/internet-docs/ial/ial_lederman_etal_06.pdf | url-status = dead }}</ref>

] and ] microbicides, such as ], ] and Savvy™ (1.0% C31G), act by disrupting the ], ] or ] of microorganisms. Since detergent microbicides also tend to kill host cells and impair the barrier function of healthy ] surfaces, they are less desirable than other agents. Additionally, clinical trials conducted to date have not demonstrated these agents to be effective at preventing HIV transmission.{{Citation needed|date=October 2010}} Consequently, laboratory and clinical trials testing this class of products as microbicides have largely been discontinued.{{Citation needed|date=October 2010}}


===Vaginal defense enhancers=== ===Vaginal defense enhancers===
Healthy vaginal ] is typically quite ]ic, with a pH value of around 4. However, the ] pH of ] can neutralize vaginal pH. One potential class of microbicides acts by reducing the pH of vaginal ]s, which may kill (or otherwise inactivate) pathogenic microorganisms. One such agent is ], a ] and microbicidal gel formulated to maintain the natural protective acidity of the vagina. Candidates in this category (including BufferGel) have proven to be ineffective in preventing HIV infection.<ref>{{Cite web

| last =
Healthy vaginal ] is typically quite ]ic, with '''pH''' values of around 4. However, the ] pH of ] can effectively neutralize vaginal pH. One potential class of microbicides acts by reducing the pH of vaginal ]s, which might either kill or otherwise inactivate pathogenic microorganisms. One such agent is ], a novel ] and microbicidal gel formulated to maintain the natural protective acidity of the vagina. Thus far, candidates in this category, including BufferGel, have proven to be ineffective in preventing HIV infection.<ref>{{Cite web
| title = Anti-HIV Gel Shows Promise in Large-scale Study in Women
| last = HIV infection
| url=http://www.hptn.org/web%20documents/HPTN035/NIAID%20HPTN%20035%20Final%20Press%20Release.pdf
| first =
| access-date = 1 April 2018
| title = Research: HIV infection
| url=http://www.hptn.org/web%20documents/HPTN035/NIAID%20HPTN%20035%20Final%20Press%20Release.pdf |archive-url= https://web.archive.org/web/20160313131115/http://www.hptn.org/web%20documents/HPTN035/NIAID%20HPTN%20035%20Final%20Press%20Release.pdf
|archive-date=13 March 2016
| accessdate = october 2010
}}</ref> }}</ref>


===Polyanions=== ===Polyanions===
]
The ] category of microbicides includes the ]s. Carrageenans are a family of linear sulfated ]s chemically related to ], which many microbes utilize as a ] for initial attachment to the ]. Thus, carrageenan and other microbicides of its class act as decoy receptors for ] binding.{{citation needed|date=April 2021}}


''Carrageenan'' preparations (such as 0.5% PRO 2000 and 3% Carraguard vaginal microbicide gels) have failed to demonstrate ] in preventing HIV transmission in ] clinical ]s. PRO 2000 was demonstrated to be safe, but it did not reduce the risk of HIV infection in women (as explained in the MDP 301 trial results, released in December 2009).<ref>{{Cite web
]
| last =

| title = Understanding the results from trials of the PRO 2000 microbicide candidate
The ] category of microbicides includes the ]s. Carrageenans are a family of linear sulfated ]s, chemically related to ], which many microbes utilize as a ] for initial attachment to the ]. Thus, carrageenan and other microbicides of its class act as decoy receptors for ] binding.
| url=http://www.avac.org/ht/d/sp/i/3426/pid/3426f

| access-date = 1 April 2018
'''Carrageenan''' preparations such as 0.5% PRO 2000 and 3% Carraguard® vaginal microbicide gels thus far have failed to demonstrate ] in preventing HIV transmission in ] clinical ]s. PRO 2000 was demonstrated to be safe, but it did not reduce the risk of HIV infection in women, as explained in the MDP 301 trial results, released in December 2009.<ref>{{Cite web
| website= AVAC
| last = HIV infection in women
|archive-url=https://web.archive.org/web/20110716023245/https://www.avac.org/ht/d/sp/i/3426/pid/3426f
| first =
|archive-date=16 July 2011
| title = Research: HIV infection in women
| url=http://www.avac.org/ht/d/sp/i/3426/pid/3426f
| accessdate = october 2010
}}</ref> Similarly, the phase III efficacy trial of Carraguard showed that the drug was safe for use but ineffective in preventing HIV transmission in women.<ref>{{Cite web }}</ref> Similarly, the phase III efficacy trial of Carraguard showed that the drug was safe for use but ineffective in preventing HIV transmission in women.<ref>{{Cite web
| last = HIV trasmission |last = HIV transmission
|title = Research: HIV transmission
| first =
|url = http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html
| title = Research: HIV trasmission
| url=http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html |archive-url = https://web.archive.org/web/20080306083337/http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html
|archive-date = 2008-03-06
| accessdate = october 2010
|url-status = dead
}}</ref> }}</ref>


'''Cellulose sulfate''' is another microbicide that was found to be ineffective in preventing the transmission of HIV. In fact, on February 1, 2007, the ] announced that two phase III trials of ] ] had been stopped because preliminary results suggested a potential increased risk of HIV in women who used the compound.<ref>{{Cite web ''Cellulose sulfate'' is another microbicide found ineffective in preventing the transmission of HIV. On February 1, 2007, the ] announced that two phase III trials of ] ] had been stopped because preliminary results suggested a potential increased risk of HIV in women who used the compound.<ref>{{Cite web
| last = Cellulose sulfate microbicide trial stopped | last = Cellulose sulfate microbicide trial stopped
| title = Research: Cellulose sulfate microbicide trial stopped
| first =
| url=https://www.who.int/mediacentre/news/statements/2007/s01/en/index.html
| title = Research: Cellulose sulfate microbicide trial stopped
| url=http://www.who.int/mediacentre/news/statements/2007/s01/en/index.html | archive-url=https://web.archive.org/web/20070208234913/http://www.who.int/mediacentre/news/statements/2007/s01/en/index.html
| url-status=dead
| accessdate = october 2010
| archive-date=February 8, 2007
}}, ]</ref> At present, there is no satisfactory explanation as to why application of cellulose sulfate was associated with a higher risk of HIV infection than ]. According to a review of microbicide drug candidates by the ] on March 16, 2007 a large number of compounds - more than 60 at the start of 2007 - are in the development pipeline.<ref>{{Cite web
| access-date = 1 April 2018
| last = Cellulose sulfate microbicide trial stopped
}}, ]</ref> There is no satisfactory explanation as to why application of cellulose sulfate was associated with a higher risk of HIV infection than ]. According to a review of microbicide drug candidates by the ] on March 16, 2007, a large number of compounds (more than 60 in early 2007) are under development;<ref>{{Cite web
| first =
| title = Research: Cellulose sulfate microbicide trial stopped | last = Cellulose sulfate microbicide trial stopped
| title = Research: Cellulose sulfate microbicide trial stopped
| url=http://www.who.int/mediacentre/news/statements/2007/s01/en/index.html
| url=https://www.who.int/mediacentre/news/statements/2007/s01/en/index.html
| accessdate = october 2010
| archive-url=https://web.archive.org/web/20070208234913/http://www.who.int/mediacentre/news/statements/2007/s01/en/index.html
}}</ref> And at the beginning of that year, five phase III trials testing different formulations were underway.
| url-status=dead
| archive-date=February 8, 2007
| access-date = 1 April 2018
}}</ref> at the beginning of that year, five phase III trials testing different formulations were underway.


===Nanoscale dendrimers=== ===Nanoscale dendrimers===
]{{clarify|date=November 2010}} ]s]] ].|alt=Chemical diagrams: one simpler and red, the other more complex and light blue]]
VivaGel is a sexual lubricant with antiviral properties manufactured by Australian pharmaceutical company Starpharma. The active ingredient is a ] ]ic molecule (which binds to viruses and prevents them from affecting an organism's cells).<ref>{{Cite news|last=Daily Telegraph c/o Australian News Network |title=Research: Daily Telegraph c/o Australian News Network |url=http://www.news.com.au/dailytelegraph/story/0,22049,22127964-5001028,00.html?from=public_rss |access-date=1 April 2018 |url-status=dead |archive-url=https://web.archive.org/web/20081022092540/http://www.news.com.au/dailytelegraph/story/0%2C22049%2C22127964-5001028%2C00.html?from=public_rss |archive-date=October 22, 2008 }}</ref> Experimental results with VivaGel indicate 85–100% effectiveness at blocking transmission of both HIV and ] in ] monkeys. It has passed the animal-testing phases of the ] in Australia and the United States, which will be followed by initial human safety tests. The ] and the ] have awarded grants totaling $25.7&nbsp;million for VivaGel's development and testing. VivaGel is being developed as a standalone microbicide gel and an intra-vaginal microbicide.<ref>{{Cite web
{{See also|Dendrimer}}
|title = VivaGel™ – Clinical trials Under Way
'''VivaGel®''' is a sexual lubricant with antiviral properties manufactured by Australian pharmaceutical company ]. The active ingredient is a ] ]ic molecule, chemicals that bind to viruses and prevent them from affecting an organism's cells.<ref>{{Cite news
|url = http://www.starpharma.com/vivagel.asp
| last = Daily Telegraph c/o Australian News Network
|website = Star Pharma
| first =
|access-date = 1 April 2018
| title = Research: Daily Telegraph c/o Australian News Network
|archive-url = https://web.archive.org/web/20080107073915/http://www.starpharma.com/vivagel.asp
| url=http://www.news.com.au/dailytelegraph/story/0,22049,22127964-5001028,00.html?from=public_rss
|archive-date = 7 January 2008
| accessdate = october 2010
|url-status = dead
}} {{Dead link|date=May 2011|bot=RjwilmsiBot}}</ref> Experimental results to date using VivaGel indicate 85-100% effectiveness at blocking transmission of both HIV and ] in ] monkeys. It has passed through animal testing phases of the ] in Australia and the United States. Initial human safety tests are to ensue. The ] and ] have awarded grants totaling $25.7 million for VivaGel's continued development and testing. VivaGel is being developed both as a standalone microbicide gel and also as an intravaginal microbicide.<ref>{{Cite web
| last = vivagel |df = dmy-all
}}</ref> It is also being evaluated for use in condoms. It is hoped that VivaGel will provide an extra resource to mitigate the ].{{citation needed|date=April 2021}}
| first =
| title = Research: vivagel
| url=http://www.starpharma.com/vivagel.asp
| accessdate = october 2010
}}</ref> VivaGel is also being evaluated for use in condoms by a leading manufacturer. VivaGel's potential benefits could in particular provide an extra resource to mitigate the current ].


In many cases, it is hoped that microbicides will block the transmission of HIV, as well as other sexually transmitted diseases, such as those caused by certain ]es (HPV) and ]es (HSV). In 2009, StarPharma released its results for a study investigating ''VivaGel''’s antiviral activity against HIV and HSV in humans by testing cervicovaginal samples in vitro (i.e., in a test tube). The compound displayed a high level of efficacy against HIV and HSV. However, while the results are encouraging, the study did not evaluate VivaGel’s effect in the body, so it is still unknown what the results mean for efficacy in women who would use the product in real-life settings. For example, the effect of sexual intercourse or semen on the gel, which oftentimes affects the protective properties of the drug, is still unknown. It should also be noted that the CAPRISA 004 trial demonstrated that topically applied tenofovir gel provided 51% protection against HSV-2.<ref>{{Cite web It is also hoped that microbicides will block the transmission of HIV and other sexually transmitted infections, such as those caused by certain ]es (HPV) and ]es (HSV). In 2009, Starpharma released its results for a study investigating VivaGel's antiviral activity against HIV and HSV in humans by testing cervico-vaginal samples ''in vitro'' (in a test tube). The compound displayed a high level of efficacy against HIV and HSV. While the results are encouraging, the study did not evaluate VivaGel's effect in the body. It is still unknown what the results mean for women who would use the product in real-life settings; for example, the effect of sexual intercourse (or semen) on the gel (which often affects the protective properties of a drug) is unknown. The ] trial demonstrated that topical tenofovir gel provided 51% protection against HSV-2.<ref>{{Cite web
| last =CAPRISA 004 | last =CAPRISA 004
| title = Research: CAPRISA 004
| first =
| url=http://clinicaltrials.gov/ct2/show/NCT00740584?term=SPL7013-003&rank=1
| title = Research: CAPRISA 004
| access-date = 1 April 2018
| url=http://clinicaltrials.gov/ct2/show/NCT00740584?term=SPL7013-003&rank=1
| accessdate = october 2010
}}</ref> }}</ref>


===Antiretrovirals=== ===Antiretrovirals===


In recent years, researchers have begun to focus on another class of microbicides, the ] (ARV) agents. ARVs work either by preventing the HIV virus from entering a human host cell, or by preventing its replication after its has already entered.<ref>http://www.caprisa.org/joomla/index.php/component/content/article/1/225</ref> Examples of ARV drugs being tested for prevention include ], ] (a ] ] of HIV ]), and UC-781.<ref>{{Cite web Researchers have begun to focus on another class of microbicides, the ] (ARV) agents. ARVs work either by preventing the HIV virus from entering a human host cell, or by preventing its replication after it has already entered.<ref>{{Cite web |url=http://www.caprisa.org/joomla/index.php/component/content/article/1/225 |title=Study Details |access-date=2010-10-01 |archive-url=https://web.archive.org/web/20100724013709/http://www.caprisa.org/joomla/index.php/component/content/article/1/225 |archive-date=2010-07-24 |url-status=dead }}</ref> Examples of ARV drugs being tested for prevention include ], ] (a ] ] of HIV ]) and UC-781.<ref>{{Cite web
| last =UC-781 | last =
| title = Ongoing Clinical Trials of Topical Microbicide Candidates (May 2011)
| first =
| url=http://www.avac.org/ht/a/GetDocumentAction/i/3109
| title = Research: UC-781
| website= AVAC
| url=http://www.avac.org/ht/a/GetDocumentAction/i/3109
| access-date = 1 April 2018
| accessdate = october 2010
|archive-url= https://web.archive.org/web/20110716023232/https://www.avac.org/ht/a/GetDocumentAction/i/3109
}}9</ref> These "next-generation" microbicides have received increasing attention and support because they are based on the same ARV drugs that are currently used to extend the length and improve the quality of lives of HIV-positive people. Additionally, ARVs are used to prevent ] of HIV from mother to child during ], and are often used to prevent HIV infection from developing immediately ] to the virus.<ref>{{Cite web
|archive-date=16 July 2011
| last =BasedMicrobicides
}}9</ref> These next-generation microbicides have received attention and support because they are based on the same ARV drugs currently used to extend the survival (and improve the quality of life) of HIV-positive people. ARVs are also used to prevent ] of HIV from mother to child during ], and are used to prevent HIV infection from developing immediately ] to the virus.<ref name="global-campaign"/> Such ARV-based compounds could be formulated into ] microbicides to be administered locally in the rectum or vagina or systemically through oral or injectable formulations (]). ARV-based microbicides may be formulated as long-acting vaginal rings, gels and films. The results of the first efficacy trial of an ARV-based microbicide, CAPRISA 004, tested 1% tenofovir in gel form to prevent male-to-female HIV transmission. The trial showed that the gel (which was applied topically to the vagina), was 39% effective at preventing HIV transmission.<ref name="global-campaign">{{Cite web
| first =
| title = Research:BasedMicrobicides |last = BasedMicrobicides
| url=http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides |title = Research:BasedMicrobicides
|url = http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides
| accessdate = october 2010
|archive-url = https://web.archive.org/web/20110717161903/http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides
}}.pdf</ref> Such ARV-based compounds could be formulated into ] microbicides to be administered locally in the rectum or vagina or systemically through oral or injectable formulations, which are also known as ]. ARV-based microbicides may be formulated as long-acting vaginal rings, gels and films. The results of the first efficacy trial of an ARV-based microbicide, CAPRISA 004, tested 1% tenofovir in a gel vehicle to prevent male to female HIV transmission. The trial showed that the gel, which was applied topically to the vagina, was 39% effective at preventing HIV transmission.<ref>{{Cite web
|archive-date = 2011-07-17
| last =BasedMicrobicides
|url-status = dead
| first =
}}</ref> CAPRISA 004 was the 12th microbicide-efficacy study to be completed, and the first to demonstrate a significant reduction in HIV transmission. The results of this trial are ] and offer ] that ARVs, topically applied to the vaginal mucosa, can offer protection against HIV (and other) ]s.<ref name="global-campaign" />
| title = Research:BasedMicrobicides
| url=http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides
| accessdate = october 2010
}}</ref> CAPRISA 004 was the 12th microbicide efficacy study to be completed and the first to demonstrate a significant reduction in HIV transmission. The results of this trial are ] and offer ] that ARVs topically applied to the vaginal mucosa can offer protection against HIV and potentially other ]s.<ref>{{Cite web
| last =BasedMicrobicides
| first =
| title = Research:BasedMicrobicides
| url=http://www.global-campaign.org/clientfiles/FS-ARV-BasedMicrobicides
| accessdate = october 2010
}}</ref>


==Formulations== ==Formulations==


Most of the '''first generation''' microbicides were formulated as semi-solid systems, such as gels, tablets, films, or creams, and were designed to be applied to the vagina before every act of intercourse. However, vaginal rings have the potential to provide long-term controlled release of microbicide drugs. Long-acting formulations, like vaginal rings, are potentially advantageous since they could be easy to use, requiring replacement only once a month. This ease of use could prove very important to make sure that products are used properly. In 2010, the ] began the first study in Africa to test the safety and acceptability of a vaginal ring containing dapivirine.<ref>{{Cite web Most of the '''first generation''' microbicides were formulated as semi-solid systems, such as gels, tablets, films, or creams, and were designed to be applied to the vagina before every act of intercourse. However, vaginal rings have the potential to provide long-term controlled release of microbicide drugs. Long-acting formulations, like vaginal rings, are potentially advantageous since they could be easy to use, requiring replacement only once a month. This ease of use could prove very important to make sure that products are used properly. In 2010, the ] began the first study in Africa to test the safety and acceptability of a vaginal ring containing dapivirine.<ref>{{Cite web
| last = control to fight AIDS |last = control to fight AIDS
|title = Research:New vaginal ring borrows from birth control to fight AIDS
| first =
|url = https://www.google.com/hostednews/afp/article/ALeqM5iZIqphwxvTmJxxhCRibhNPEtsL2Q
| title = Research:New vaginal ring borrows from birth control to fight AIDS
| url=http://www.google.com/hostednews/afp/article/ALeqM5iZIqphwxvTmJxxhCRibhNPEtsL2Q AFP: |archive-url = https://web.archive.org/web/20100611063830/http://www.google.com/hostednews/afp/article/ALeqM5iZIqphwxvTmJxxhCRibhNPEtsL2Q
| accessdate = october 2010 |archive-date = 2010-06-11
|url-status = dead
}}</ref> Drugs might also be administered systemically through injectable or oral formulations known as PrEP. Injectable formulations may be desirable since they could be administered infrequently, possibly once a month. It is likely, however, that such products would need to be monitored closely and would be available only through prescription. This approach also carries the risk of emergence of ARV-resistant strains of HIV.<ref>{{Cite web }}</ref> Drugs might also be administered systemically through injectable or oral formulations known as PrEP. Injectable formulations may be desirable since they could be administered infrequently, possibly once a month. It is likely, however, that such products would need to be monitored closely and would be available only through prescription. This approach also carries the risk of emergence of ARV-resistant strains of HIV.<ref>{{Cite web
| last = global-campaign | last = global-campaign
| title = Research:global-campaign
| first =
| title = Research:global-campaign | url=http://www.global-campaign.org/clientfiles/FS-ARV-Prev.pdf
| access-date = 1 April 2018
| url=http://www.global-campaign.org/clientfiles/FS-ARV-Prev.pdf
| accessdate = october 2010
}}</ref> }}</ref>


Substantial numbers of men who have sex with men in ] use lubricants containing nonoxynol-9.{{Citation needed|date=October 2010}} This suggests that they might be receptive to the concept of using topical rectal microbicides if such products were to become commercially available.<ref>{{Cite web Substantial numbers of men who have sex with men in ] use lubricants containing nonoxynol-9.{{Citation needed|date=October 2010}} This suggests that they might be receptive to the concept of using topical rectal microbicides if such products were to become commercially available.<ref>{{cite journal | vauthors = Carballo-Diéguez A, O'Sullivan LF, Lin P, Dolezal C, Pollack L, Catania J | title = Awareness and attitudes regarding microbicides and Nonoxynol-9 use in a probability sample of gay men | journal = AIDS and Behavior | volume = 11 | issue = 2 | pages = 271–6 | date = March 2007 | pmid = 16775772 | doi = 10.1007/s10461-006-9128-0 | s2cid = 2722261 }}</ref> However, the development of rectal microbicides is not as advanced as that of vaginal microbicides. One reason for this is that the rectum has a thinner epithelium, greater surface area and lower degree of elasticity than that of the vagina. Due to these factors, a microbicidal preparation that is effective when applied vaginally might have a different degree of effectiveness when applied rectally.<ref>{{Cite web
| last = Carballo | last = global-campaign
| title = global-campaign
| first = Diéguez, A., et al
| url=http://www.global-campaign.org/rectal.htm#vaginal
| title = (2006) Awareness and Attitudes Regarding Microbicides and Nonoxynol-9, in a Probability Sample of Gay Men AIDS and Behavior PMID 16775772
| access-date = 1 April 2018
| url=http://www.springerlink.com/content/x3l64412w7262206/
| accessdate = october 2010
}}</ref> However, the development of rectal microbicides is not as advanced as that of vaginal microbicides. One reason for this is that the rectum has a thinner epithelium, greater surface area and lower degree of elasticity than that of the vagina. Due to these factors, a microbicidal preparation that is effective when applied vaginally might have a different degree of effectiveness when applied rectally.<ref>{{Cite web
| last = global-campaign
| first =
| title = global-campaign
| url=http://www.global-campaign.org/rectal.htm#vaginal
| accessdate = october 2010
}}</ref> In January 2010, the National Institutes of Health awarded two grants totaling $17.5 million to the ] to fund research into rectal microbicides.<ref>{{cite news }}</ref> In January 2010, the National Institutes of Health awarded two grants totaling $17.5 million to the ] to fund research into rectal microbicides.<ref>{{cite news
| url=http://www.post-gazette.com/pg/10009/1027004-114.stm#ixzz0cFx8ZcNr | url=http://www.post-gazette.com/pg/10009/1027004-114.stm#ixzz0cFx8ZcNr
Line 194: Line 149:
| last=Templeton | last=Templeton
| date=2010-01-09 | date=2010-01-09
}}</ref> That research will include investigations into product acceptability of rectal microbicides with ] men ages 18 to 30 years old. }}</ref> That research will include investigations into product acceptability of rectal microbicides with ] men ages 18 to 30 years old.{{citation needed|date=April 2021}}


Ultimately, successful topical microbicides might simultaneously employ multiple modes of action. In fact, long-acting formulations such as vaginal rings could provide the technology needed to deliver multiple active ingredients with different mechanisms of action. Ultimately, successful topical microbicides might simultaneously employ multiple modes of action. In fact, long-acting formulations such as vaginal rings could provide the technology needed to deliver multiple active ingredients with different mechanisms of action.{{citation needed|date=April 2021}}


==Completed clinical trials== ==Completed clinical trials==


A major breakthrough in microbicide research, announced in July 2010, proved that an ARV-based microbicide does work. A trial led by the Centre for the AIDS Programme of Research in South Africa (CAPRISA), conducted in South Africa, demonstrated that the ARV tenofovir, when used in a vaginal gel, was 39% effective at preventing HIV transmission from men to women during sex.<ref>{{Cite web A major breakthrough in microbicide research, announced in July 2010, reported that an ARV-based microbicide gel could partially prevent HIV. A trial led by the Centre for the AIDS Programme of Research in South Africa (CAPRISA), conducted in South Africa, demonstrated that the ARV tenofovir, when used in a vaginal gel, was 39% effective at preventing HIV transmission from men to women during sex.<ref name="caprisa">{{Cite web
| last = caprisa | website = Caprisa
| title = Caprisa 004 Study Details
| first =
| url=http://www.caprisa.org/joomla/index.php/component/content/article/1/225
| title = caprisa
| access-date = 1 April 2018
| url=http://www.caprisa.org/joomla/index.php/component/content/article/1/225
|archive-url=https://web.archive.org/web/20110314001454/http://www.caprisa.org/joomla/index.php/component/content/article/1/225
| accessdate = october 2010
|archive-date=14 March 2011
}}</ref> }}</ref>


=== {{anchor|Tenofovir gel, CAPRISA 004}}Tenofovir gel ===
*
]

In July 2010 the ] (CAPRISA) released results of a study establishing proof of concept that an ARV-based, topical microbicide can reduce the likelihood of HIV transmission. The trial, ], was conducted among 889 women to evaluate the ability of 1% tenofovir gel to prevent male-to-female HIV transmission. The study found a 39% lower HIV infection rate in women using 1% tenofovir gel compared with women using a placebo gel. In addition, tenofovir gel was shown to be safe as tested.<ref name="caprisa" /> The results of the ] trial provide statistically significant evidence that ARVs, topically applied to the vaginal mucosa, can offer protection against HIV and (potentially) other pathogens. During the study, 38 of the women who used the tenofovir gel acquired HIV and 60 women who used a placebo gel became HIV-infected. No tenofovir-resistant virus was detected in the women who acquired HIV infection during the study. In addition to demonstrating efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents the transmission of herpes simplex virus type 2 (HSV-2). HSV-2 is a lifelong, incurable infection which can make those infected with the virus two-to-three times more likely to acquire HIV. Data collected during the CAPRISA 004 study indicate that tenofovir gel provided 51% protection against HSV-2. Tenofovir, developed by Gilead Sciences, is a nucleotide reverse-transcriptase inhibitor (NRTI) which interferes with the replication of HIV and is approved in tablet form for use in combination with other ARVs to treat HIV. CAPRISA 004 was a collaboration among CAPRISA, ] and ]. It was funded by the ] (USAID) and the South African Department of Science and Technology's ].{{citation needed|date=April 2021}}
=== Tenofovir gel,CAPRISA 004 ===
{{Main|CAPRISA 004}}
]
In July 2010, the ] (CAPRISA) released results of a study that established "''proof of concept''" that an ARV-based topical microbicide can reduce the likelihood of HIV transmission. The trial, CAPRISA 004, was conducted in South Africa among 889 women to evaluate the ability of 1% tenofovir gel to prevent male-to-female HIV transmission. In an important milestone for HIV prevention, the CAPRISA 004 study found a 39% lower HIV infection rate in women using 1% tenofovir gel as compared to those women using a placebo gel. In addition, tenofovir gel was shown to be safe as tested.<ref>{{Cite web
| last = caprisa
| first =
| title = caprisa
| url=http://www.caprisa.org/joomla/index.php/component/content/article/1/225
| accessdate = october 2010
}}</ref> The results of the ] trial provide statistically significant evidence that ARVs topically applied to the vaginal mucosa can offer protection against HIV and potentially other pathogens. During the course of the study, 38 of the women who used the tenofovir gel acquired HIV, whereas 60 women who used a placebo gel became HIV-infected. No tenofovir-resistant virus was detected in the women who acquired HIV infection during the study. In addition to showing efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents transmission of herpes simplex virus type 2 (HSV-2). HSV-2 is a lifelong and incurable infection that can make those infected with the virus two-to-three times more likely to acquire HIV. Data collected during the CAPRISA 004 study indicate that tenofovir gel provided 51% protection against HSV-2. Tenofovir, developed by Gilead Sciences, Inc., is a well-established nucleotide reverse transcriptase inhibitor (NRTI) that interferes with the replication of HIV and is approved in tablet form for use in combination with other ARVs to treat HIV. CAPRISA 004 was a collaboration among CAPRISA, ] and ]. It was funded by the ] (USAID) and the South African Department of Science and Technology's ].


=== PRO 2000 === === PRO 2000 ===
{{See also|PRO 2000}}

] ]
Results released in February 2009 from a clinical trial of PRO 2000 (]), a vaginal-microbicide gel (0.5%), sparked hope that it might provide modest protection against HIV.<ref>{{Cite journal

| last = Nature News
Results released in February 2009 from a clinical trial of PRO 2000 (], Lexington, Massachusetts), a vaginal microbicide gel (0.5% dose), sparked hope that it might provide modest protection against HIV.<ref>{{Cite web
| last = Nature News: | title = Nature News: Microbicide gel may help against HIV
| journal = Nature
| first =
| url=http://www.nature.com/news/2009/090210/full/news.2009.91.html
| title = Nature News: Microbicide gel may help againstn HIV
| access-date = 1 April 2018
| url=http://www.nature.com/news/2009/090210/full/news.2009.91.html
| doi = 10.1038/news.2009.91
| accessdate = october 2010
| year = 2009
}}</ref> However, the results of a larger trial released in December 2009 showed that PRO 2000 was safe as administered but was not effective at reducing the risk of HIV infection. That trial, known as MDP 301, was sponsored by the Microbicides Development Programme. MDP 301 was conducted in South Africa, Tanzania, Uganda and Zambia and included more than 9,300 women volunteers. No significant difference was found in the number of women who contracted HIV in the group given PRO 2000 compared to the group given the placebo.<ref>{{Cite web
| doi-access = free
| last = medicalnewstoday
}}</ref> The results of a larger trial released in December 2009 showed that PRO 2000 was safe as administered, but was ineffective in reducing the risk of HIV infection. That trial (MDP 301) was sponsored by the Microbicides Development Programme. MDP 301 was conducted in South Africa, Tanzania, Uganda and Zambia with more than 9,300 women volunteers. No significant difference was found in the number of women who contracted HIV in the group given PRO 2000 compared to the group given a placebo.<ref>{{Cite web
| first =
| website = Medical News Today
| title = medicalnewstoday
| url=Microbicide Gel Ineffective At Preventing HIV Infection Among Women, Study Finds, http://www.medicalnewstoday.com/articles/174282.php | title = Microbicide Gel Ineffective At Preventing HIV Infection Among Women, Study Finds
| url= http://www.medicalnewstoday.com/articles/174282.php
| access-date = 1 April 2018
| accessdate = october 2010
|archive-url=https://web.archive.org/web/20110614131746/http://www.medicalnewstoday.com/releases/174282.php
}}</ref> While this trial did not result in an effective product, it served as a model for future HIV prevention trials as it provided critical scientific information as well as important lessons from the extensive social science component and the comprehensive community engagement and preparation undertaken by the trial staff.<ref>{{Cite web
|archive-date=14 June 2011
| last = avac.
}}</ref> While this trial did not result in an effective product, it served as a model for future HIV-prevention trials; it provided scientific information and lessons from its social-science component, community engagement and preparation undertaken by the trial staff.<ref>{{Cite web
| first =
| title = avac.org | website = AVAC
| title = Understanding the results from trials of the PRO 2000 microbicide candidate
| url=http://www.avac.org/ht/d/sp/i/3426/pid/3426/articles/174282.php
| url=http://www.avac.org/ht/d/sp/i/3426/pid/3426/articles/174282.php
| accessdate = october 2010
| access-date = 1 April 2018
|archive-url=https://web.archive.org/web/20110725025925/http://www.avac.org/ht/d/sp/i/3426/pid/3426/articles/174282.php
|archive-date=25 July 2011
}}</ref> }}</ref>


=== Carrageenan === === Carrageenan ===
Carrageenan may prevent HPV and HSV transmission, but not HIV. See ]
{{See also|Carrageenan}}

The phase III clinical trial for carrageenan-based Carraguard showed that it had no statistical effect on HIV infection, according to results released in 2008. The study did show that the gel was safe, with no side effects or increased risks. The trial also provided valuable information about usage patterns in trial participants.<ref>{{Cite web
The phase III clinical trial for carrageenan-based Carraguard showed that it had no statistical effect on HIV infection, according to results released in 2008. The study showed that the gel was safe, with no side effects or increased risks. The trial also provided information about usage patterns in trial participants.<ref>{{Cite web
| title = Trial Shows Anti-HIV Microbicide Is Safe, but does Not Prove it Effective | title = Trial Shows Anti-HIV Microbicide Is Safe, but does Not Prove it Effective
| work = Population Council | work = Population Council
| accessdate = 2008-03-12 | access-date = 2008-03-12
| date = 2008-02-18 | date = 2008-02-18
| url = http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html | url = http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html
| archive-date = 2008-03-06
| archive-url = https://web.archive.org/web/20080306083337/http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html
| url-status = dead
}}</ref><ref> }}</ref><ref>
{{Cite web {{Cite web
| title = Experimental Microbicide Carraguard Does Not Provide Protection Against HIV, Study Finds |title = Experimental Microbicide Carraguard Does Not Provide Protection Against HIV, Study Finds
| work = kaisernetwork.org |work = kaisernetwork.org
| accessdate = 2008-03-12 |access-date = 2008-03-12
| date = 2008-02-20 |date = 2008-02-20
| url = http://www.kaisernetwork.org/Daily_reports/rep_index.cfm?DR_ID=50494 |url = http://www.kaisernetwork.org/Daily_reports/rep_index.cfm?DR_ID=50494
|archive-url = https://web.archive.org/web/20090721161515/http://www.kaisernetwork.org/Daily_reports/rep_index.cfm?DR_ID=50494
|url-status = dead
|archive-date = 2009-07-21
}}</ref> }}</ref>


=== Nonoxynol-9 === === Nonoxynol-9 ===

]
], a ], is ineffective as a topical microbicide in preventing HIV infection. Although nonoxynol-9 has been shown to increase the risk of HIV infection when used frequently by women at high risk of infection, it remains a contraceptive option for women at low risk.<ref name="WHO 2002">{{cite web|author=World Health Organization|year=2002|title=HIV/AIDS Topics: Microbicides|url=https://www.who.int/hiv/topics/microbicides/microbicides/en/|location=Geneva|publisher=World Health Organization|access-date=August 28, 2006}}</ref>
Substantial clinical evidence suggests that regular use of a commonly used spermicide called ] actually increases the risk of HIV infection. Early in the HIV/AIDS epidemic, it was discovered that nonoxynol-9 could block the replication of HIV in laboratory tests. For more than a decade, public health professionals recommended nonoxynol-9 for use as a topical microbicide, and many condom and sexual lubricant brands incorporated nonoxynol-9 for this purpose. However, subsequent clinical research showed that nonoxynol-9 can result in the formation of erosions or sores in the vagina or rectum, which are now believed to serve as points of entry for HIV and other sexually transmitted diseases. Consequently, there is now a broad consensus in the public health community that nonoxynol-9 should NOT be used as a topical microbicide.<ref>{{Cite web
| last = WHO
| first =
| title =WHO Microbicide overview
| url=http://www.who.int/hiv/topics/microbicides/microbicides/en/
| accessdate = october 2010
}}</ref>


==Current research== ==Current research==
Significant efforts are under way to develop safe and effective topical microbicides. Several different gel formulations are currently undergoing testing in phase III clinical efficacy trials, and about two dozen other products are in various phases of development.<ref>{{Cite web Efforts are underway to develop safe and effective topical microbicides. Several different gel formulations are currently undergoing testing in phase III clinical efficacy trials, and about two dozen other products are in various phases of development.<ref>{{Cite web
| last = avac | website = AVAC
| title = Microbicide Clinical Trials
| first =
| url=http://www.avac.org//ht/d/sp/i/3512/pid/3512
| title =avac
| access-date = 1 April 2018
| url=http://www.avac.org//ht/d/sp/i/3512/pid/3512 ongoing microbicide clinical trials
|archive-url= https://web.archive.org/web/20110716023105/http://www.avac.org//ht/d/sp/i/3512/pid/3512
| accessdate = october 2010
|archive-date=16 July 2011
}}</ref><ref>Global Campaign for Microbicides </ref> Results from CAPRISA 004, while promising, may need to be confirmed by other clinical trials before the microbicide tenofovir gel is made available to the public.<ref>{{Cite web }}</ref><ref>Global Campaign for Microbicides </ref> Results from CAPRISA 004, while promising, may need to be confirmed by other clinical trials before the microbicide tenofovir gel is made available to the public.<ref>{{Cite web
| last =PEPFAR | website =PEPFAR
| title =PEPFAR Statement on CAPRISA 004 Trial
| first =
| url=http://www.pepfar.gov/press/releases/2010/144861.htm
| title =PEPFAR Statement on CAPRISA 004 Trial
| access-date = 1 April 2018
| url=http://www.pepfar.gov/press/releases/2010/144861.htm PEPFAR
|archive-url=https://web.archive.org/web/20121014050452/http://www.pepfar.gov/press/releases/2010/144861.htm
| accessdate = october 2010
|archive-date=14 October 2012
}}</ref> This decision rests with regulators, particularly in South Africa. In 2013, the VOICE study (MTN 003), another large-scale trial, is scheduled to release results. VOICE is evaluating three different strategies to prevent HIV in women: one ARV-based microbicide and two different regimens that consist of taking oral ARVs on a daily basis.<ref>{{Cite web
}}</ref> This decision rests with regulators, particularly in South Africa. In 2013, the VOICE study (MTN 003), another large-scale trial, is scheduled to release results. VOICE is evaluating three different strategies to prevent HIV in women: one ARV-based microbicide and two regimens consisting of oral ARVs on a daily basis.<ref>{{Cite web
| last =AVAC
| first = | website =AVAC
| title =AVAC-About Microbicides | title =AVAC-About Microbicides
| url=http://www.avac.org/ht/d/sp/i/257/pid/257 AVAC-About Microbicides | url=http://www.avac.org/ht/d/sp/i/257/pid/257
| access-date = 1 April 2018
| accessdate = october 2010
|archive-url=https://web.archive.org/web/20110725025346/http://www.avac.org/ht/d/sp/i/257/pid/257
}}</ref> The VOICE trial is testing 1% tenofovir vaginal gel in a once-daily formulation. It is not known at this time if VOICE will be considered a confirmatory trial for CAPRISA 004, which used a different dosing strategy.<ref>{{Cite web
|archive-date=25 July 2011
| last =VOICE
}}</ref> The VOICE trial is testing 1% tenofovir vaginal gel in a once-daily formulation. It is not known at this time if VOICE will be considered a ] for CAPRISA 004, which used a different dosing strategy.<ref>{{Cite web
| first =
| website = MTN
| title =VOICE backgrounder
| title =Vaginal and Oral Interventions to Control the Epidemic
| url=http://www.mtnstopshiv.org/news/studies/mtn003/backgrounder VOICE backgrounder
| url=http://www.mtnstopshiv.org/news/studies/mtn003/backgrounder
| accessdate = october 2010
| access-date = 1 April 2018
}}</ref> Products known as Pre-Exposure Prophylaxis, or PrEP, are also being tested at various stages of the development process. These products, administered orally or via injection, would contain ARVs to protect HIV-negative people from becoming infected. In this strategy, individuals would receive ARVs before they were exposed to HIV, with the goal of lowering their risk or preventing of infection.<ref>{{Cite web
|archive-url=https://web.archive.org/web/20161127165358/http://www.mtnstopshiv.org/news/studies/mtn003/backgrounder
| last =AVAC
|archive-date=27 November 2016
| first =
}}</ref> Products known as Pre-Exposure Prophylaxis, or PrEP, are also being tested at various stages of the development process. These products, administered orally or via injection, would contain ARVs to protect HIV-negative people from becoming infected. Individuals would receive ARVs before they were exposed to HIV, with the goal of lowering their risk or preventing infection.<ref>{{Cite web
| title =AVAC-About PrEP
| website =AVAC
| url=http://www.avac.org/ht/d/sp/i/266/pid/266 AVAC-About PrEP
| accessdate = october 2010 | title = About PrEP
| url=http://www.avac.org/ht/d/sp/i/266/pid/266
}}</ref> One of the potential advantages of PrEP is that an individual could use it autonomously, without the need to negotiate with a partner, and it is not dependent on the time of sex. It is hoped that those unable to negotiate condom use with their sex partners would still be able to reduce their risk of HIV infection with the use of an oral or injectable prevention drug. Current PrEP candidates in development include tenofovir and Truvada, which is a combination of two ARV compounds — tenofovir and emtricitabine.<ref>{{Cite web
| access-date = 1 April 2018
| last =AVAC
|archive-url=https://web.archive.org/web/20120306230316/http://avac.org/ht/d/sp/i/266/pid/266
| first =
|archive-date=6 March 2012
| title =AVAC-Ongoing PrEP Trials
}}</ref> One of the potential advantages of PrEP is that an individual could use it autonomously (without the need to negotiate with a partner), and it is not dependent on the time of sex. It is hoped that those unable to negotiate condom use with their sexual partners would be able to reduce their risk of HIV infection with the use of an oral (or injectable) prophylactic drug. Current PrEP candidates in development include tenofovir and Truvada (a combination of two ARV compounds, tenofovir and emtricitabine).<ref name="avac">{{Cite web
| url=http://www.avac.org/ht/d/sp/i/3507/pid/3507
| website =AVAC
| accessdate = october 2010
| title = Ongoing PrEP Trials
}}</ref> One potential risk of the PrEP approach is that drugs present in the systemic circulation might, over time, create ARV-resistant HIV strains.<ref>{{Cite web
| url=http://www.avac.org/ht/d/sp/i/3507/pid/3507
| last =AVAC
| access-date = 1 April 2018
| first =
|archive-url= https://web.archive.org/web/20120306233853/http://www.avac.org/ht/d/sp/i/3507/pid/3507
| title =AVAC-Ongoing PrEP Trials
|archive-date=6 March 2012
| url=http://www.avac.org/ht/d/sp/i/3507/pid/3507
}}</ref> One potential risk of the PrEP approach is that drugs present in systemic circulation might, over time, create ARV-resistant HIV strains.<ref name="avac" />
| accessdate = october 2010
}}</ref>


==Social factors== ==Social factors==
]s are an effective method for blocking the transmission of most sexually transmitted infections (with HPV a notable exception).{{Citation needed|date=October 2010}} However, a variety of social factors (including, but not limited to, the sexual disempowerment of women in many cultures) limit the feasibility of condom use.<ref>{{Cite web
|website = U.N.Declaration
|title = 2007 U.N.Declaration of Commitment on HIV/AIDS and Political Declaration on HIV/AIDS
|url = http://data.unaids.org/pub/Report/2007/20070418_sg_%20progress_report__en.pdf
|archive-url = https://web.archive.org/web/20090325232512/http://data.unaids.org/pub/Report/2007/20070418_sg_%20progress_report__en.pdf
|archive-date = 2009-03-25
|url-status = dead
}}</ref> Thus, topical microbicides might provide a useful woman-initiated alternative to condoms.{{citation needed|date=January 2023}}


Some sub-Saharan African cultures view vaginal lubrication as undesirable.<ref>{{Cite web
]s are a highly effective method for blocking the transmission of most sexually transmitted diseases (with HPV being a notable exception).{{Citation needed|date=October 2010}} However a variety of social factors, including, but not limited to, the sexual disempowerment of women in many cultures, tend to limit the feasibility of condom use.<ref>{{Cite web
|last = Hyena
| last =U.N.Declaration
|first = H.
| first =
|title = "Dry sex" worsens AIDS numbers in southern Africa
| title =2007 U.N.Declaration of Commitment on HIV/AIDS and Political Declaration on HIV/AIDS
|url = http://www.salon.com/health/sex/urge/world/1999/12/10/drysex/
| url=http://data.unaids.org/pub/Report/2007/20070418_sg_%20progress_report__en.pdf
|date = 10 December 1999
| accessdate = october 2010
|access-date = 1 April 2018
}}: focus on progress over the past 12 months</ref> Thus, topical microbicides might provide a useful woman-initiated alternative to condoms. Some sub-Saharan African cultures view vaginal lubrication as undesirable.<ref>{{Cite web
|archive-url = https://web.archive.org/web/20070825014920/http://www.salon.com/health/sex/urge/world/1999/12/10/drysex/
| last =Hyena,
|archive-date = 25 August 2007
| first = H.
|url-status = live
| title ="Dry sex" worsens AIDS numbers in southern Africa
|df = dmy-all
| url=http://www.salon.com/health/sex/urge/world/1999/12/10/drysex/
}}</ref> Since some topical microbicide formulations currently under development function as lubricants, such "dry sex" traditions may pose a barrier to the implementation of topical microbicidal programs. Recent data on product acceptability, however, show that many men and women enjoy using gels during sex that would contain a microbicidal drug.<ref name="avac" />
| accessdate = Dec 10 1999
}}</ref> Since some topical microbicide formulations currently under development function as lubricants, such dry sex traditions may pose a barrier to the implementation of topical microbicide programs. Recent data on product acceptability, however, show that many men and women enjoy using gels that would contain the microbicide drug during sex.<ref>{{Cite web
| last =AVAC
| first =
| title =AVAC-Ongoing PrEP Trials
| url=http://www.avac.org/ht/d/sp/i/3507/pid/3507
| accessdate = october 2010
}}</ref>


==See also== == See also ==
{{Commons category|Antiseptics|}} * ]
* ]
{{Commons category|Supramolecolar chemistry}}
* ] * ]
* ]
* ] * ]
* ]
* ]
* ]
* ]
* ]s
* ]


==References== == References ==
{{Reflist|2}} {{reflist|30em}}


==External links== == External links ==
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{{Microbicides for sexually transmitted diseases}}
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{{DEFAULTSORT:Microbicides For Sexually Transmitted Diseases}} {{DEFAULTSORT:Microbicides For Sexually Transmitted Diseases}}
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