Microbicides for sexually transmitted diseases 425158 212036165 2008-05-13T04:06:02Z 67.161.115.54 /* Mechanisms of action */ {{Inappropriate tone|date=December 2007}} A major effort is currently underway to develop [[topical]] microbicides for sexually transmitted diseases, that might be applied to [[condom]]s or directly to the genitals to block [[sexually transmitted disease]]s (STDs), such as [[HIV]]. It is hoped that these products could be produced inexpensively and distributed freely worldwide. A successful [[microbicide]] product would be of particular benefit to women in countries where culturally-accepted, abusive relationships make it difficult or impossible for women to negotiate condom use. ==Nonoxynol-9== Early in the HIV/[[AIDS]] epidemic, it was discovered that a commonly-used [[spermicide]] called [[nonoxynol-9]] can 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's irritating detergent effects can result in the formation of erosions or sores in the vagina or rectum. Such sores are now believed to serve as sites of entry for HIV and other STDs and there is substantial clinical evidence suggesting that regular use of nonoxynol-9 actually ''increases'' the risk of HIV infection. Consequently, there is now a broad consensus in the public health community that '''nonoxynol-9 should NOT be used as a topical microbicide.'''<ref>[http://www.who.int/hiv/topics/microbicides/microbicides/en/ WHO Microbicide overview] </ref> ==Current progress== Despite the false start with nonoxynol-9, there has been significant recent progress toward the development of safe and effective topical microbicides. Several different gel formulations, including [http://www.indevus.com/site/index.php?option=com_content&task=view&id=28&Itemid=42 PRO 2000], and [http://www.reprotect.com/products.shtml BufferGel] are currently undergoing testing in phase III clinical efficacy trials and about two dozen other products are in various phases of development <ref>Alliance for Microbicide Development [http://www.microbicide.org/ clinical pipeline database] </ref><ref>Global Campaign for Microbicides [http://www.global-campaign.org/products_in_the_pipeline.htm Product Pipeline List]</ref>. In most cases, it is hoped that the gels will block the transmission of HIV, as well as other STDs, such as [[human papillomavirus]]es (HPVs) and [[herpes simplex virus]]es (HSVs). For example, [[carrageenan]], the active ingredient in Carraguard, has been shown to block the replication of all three virus types in laboratory studies. Interestingly, carrageenan is already in use as a gelling agent in some over the counter [[personal lubricant]] products, such as [http://www.bioglide.com/en/index.html Bioglide], [[Divine lubricants|Divine]], and [http://www.oceanusbrands.com/ Oceanus Carrageenan] brands. [[Viva Gel]] is a particularly unique microbicide in that its active ingredient is a [[nanoscale]] [[dendrimer]] and 85-100% effective at stopping the transmission of both [[HIV]] and [[genital herpes]] in [[macaque]] monkies.{{Clarifyme|date=March 2008}} The [[NIH]] and [[NIAID]] have awarded grants totaling $25.7 million for [http://www.starpharma.com/vivagel.asp VivaGel's] continued development and testing. [http://www.starpharma.com/vivagel.asp VivaGel] is also being evaluated for use in condoms by a leading manufacturer. The phase III clinical trial for [[carrageenan]]-based [[Carraguard]] showed that it has no statistical effect on HIV infection. The researchers point out that the study at least proved that the gel is safe, with no side effects or increased risk, and provided valuable information about usage patterns in the test subjects.<ref>{{Cite web | title = Trial Shows Anti-HIV Microbicide Is Safe, but does Not Prove it Effective | work = Population Council | accessdate = 2008-03-12 | date = 2008-02-18 | url = http://www.popcouncil.org/mediacenter/newsreleases/Carraguard_Findings.html }}</ref><ref> {{Cite web | title = Experimental Microbicide Carraguard Does Not Provide Protection Against HIV, Study Finds | work = kaisernetwork.org | accessdate = 2008-03-12 | date = 2008-02-20 | url = http://www.kaisernetwork.org/Daily_reports/rep_index.cfm?DR_ID=50494 }}</ref> {{see|Carrageenan#Sexual lubricant and microbicide}} ==Mechanisms of action== Detergent microbicides, such as nonoxynol-9, [[sodium dodecyl sulfate]] and [http://www.biosyn-inc.com Savvy], can function by disrupting the outer coat or lipid [[Biological membrane|membrane]] of viruses and bacteria. Since detergent microbides also tend to kill cells and impair the '''barrier function''' of healthy mucosal surfaces, they are less preferred. Healthy vaginal pH is typically quite acidic (pH 4). However, the alkaline pH of [[semen]] can effectively neutralize vaginal pH. It is hoped that candidate microbicides such as Buffergel, lime juice <ref>[http://www.economist.com/science/displaystory.cfm?story_id=6849906 Bitter fruit: Another idea for stopping AIDS falls flat]. ''The Economist'', April 27, 2006</ref> and preparations of live ''[[Lactobacillus]]'' bacteria might act by promoting acidic vaginal pH, which can in turn inactivate pathogenic viruses and bacteria. Another microbicide class is embodied by Carraguard and PRO 2000, which are expected to function by preventing microbes from binding to the surface of cells. Carrageenan chemically resembles cellular [[heparan sulfate]] [[polysaccharide]]s, which many microbes utilize for initial attachment to cell surfaces. Thus, carrageenan and other microbicides of its class act as decoys for virus binding. Drugs that specifically target the molecular features of HIV are also being investigated as topical microbicides. In some instances, HIV drugs that cannot be absorbed orally are under consideration, since they could conceivably function when applied topically. Ultimately, successful topical microbicides may simultaneously employ multiple modes of action. ==Microbicide formulations== Most of the first generation microbicides undergoing development are formulated as semi-solid systems, such as gels or creams, and are designed to be applied to the vagina via an applicator before every act of intercourse. [[Vaginal ring]] devices are also being developed that have the potential to provide long-term controlled release of microbicides. ==Social factors== Condoms are a highly effective method for blocking the transmission of most STDs (with [[HPV]]s being a notable exception). However a variety of social factors, including the sexual disempowerment of women in many cultures, tend to limit the feasibility of condom use. Thus, topical microbicides might provide a useful woman-controlled alternative to condoms, particularly if the microbicides could be applied without the knowledge of male partners. Many sub-Saharan African cultures view vaginal lubrication as undesirable <ref>Hyena, H. (1999) [http://www.salon.com/health/sex/urge/world/1999/12/10/drysex/ "Dry sex" worsens AIDS numbers in southern Africa] ''Salon'', Dec 10.</ref><ref>Myer, L. et al. (2005) [http://linkinghub.elsevier.com/retrieve/pii/S1473-3099(05)70298-X Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms] ''Lancet Infectious Diseases'' 5(12):786. PMID 16310150</ref>. Since all topical microbicides currently under development function as lubricants, such [[dry sex]] traditions may pose a major barrier to the implementation of topical microbicide programs in the areas most severely affected by the HIV/AIDS epidemic. Most individuals who engage in [[anal sex]] routinely use some form of lubricant product. The fact that substantial numbers of [[gay]] men in developed countries continue to use lubricants containing nonoxynol-9 demonstrates that they are generally aware of the concept of topical microbicides and might rapidly adopt a clinically successful '''rectal microbicide''' product <ref>Carballo-DiƩguez, A., et al. (2006) [http://www.springerlink.com/content/x3l64412w7262206/ Awareness and Attitudes Regarding Microbicides and Nonoxynol-9 use in a Probability Sample of Gay Men] ''AIDS and Behavior'' PMID 16775772</ref>. Unfortunately, the development of rectal microbicides is not as advanced as that of vaginal microbicides. Several biological differences (such as the rectum's thinner epithelium, greater surface area, lower degree of elasticity) mean that a microbicide that is effective when applied vaginally might not be effective when applied rectally. Therefore, increased investment in rectal microbicide research is needed. ==References== <references/> ==See also== *[[International Rectal Microbicides Working Group]] *[[Spermicide]] *[[Cellulose sulfate]] *[[Carrageenan#Sexual_lubricant_and_microbicide|Carrageenan]] *[[Divine lubricants]] ==External links== *[http://www.global-campaign.org Information on microbicides to prevent HIV/AIDS] *[http://www.ipm-microbicides.org International Partnership for Microbicides] *[http://www.lifelube.org Rectal microbicides] *[http://www.aidschicago.org/rectalmicrobicides/ International Rectal Microbicide Advocates] *[http://www.empro.org.uk/home.php4 European Microbicides Project] *[http://www.aidsportal.org/overlay_details.aspx?nex=28 AIDSPortal page on microbicides with research, case studies and news stories] *[http://www.starpharma.com/vivagel.asp Starpharma's VivaGel Product Homepage] *[http://hivinsite.ucsf.edu/InSite?page=kbr-07-02-04 HIV InSite] Microbicides and Female-Controlled Prevention Technologies: Related Resources [[Category:Antiseptics]] [[de:Mikrobizid]]