{"id":3299,"date":"2006-05-12T08:46:02","date_gmt":"2006-05-12T07:46:02","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=3299"},"modified":"2013-12-06T18:43:41","modified_gmt":"2013-12-06T18:43:41","slug":"topical-microbicides-the-real-front-line-of-hiv-prevention","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/3299","title":{"rendered":"Topical microbicides: the real front line of HIV prevention"},"content":{"rendered":"

David Margolis, for natap.org<\/strong><\/p>\n

Topical microbicides, preparations able to kill HIV on contact and prevent infection, are a critical complement to vaccines and other prevention strategies. They can protect women, for example, who cannot protect themselves by other means. Gels are in development and testing, but a plan is needed for future approaches if the results of trials expected in 2006-07 are not encouraging.<\/strong><\/p>\n

John Moore of Cornell provided an excellent overview of what is needed in the field. A microbicide must be safe, effective, affordable, and acceptable. To accomplish this, a preparation must not damage the epithelium, not alter bacterial flora, and must not cause inflammation (as has led to increased HIV transmission following the use of past microbicides).<\/p>\n

Several HIV reverse transcriptase inhibitors, AZT-like drugs, are in development. Among them are TMC 120, UC781, and tenofovir. Reagents that block chemokine receptors such as cyanovirin, psc-rantes, and others are under study. In the SIV model, PSC-Rantes formulated in a gel protected monkeys from vaginal and rectal challenge, and did not induce inflammation. The \u0093triple-therapy\u0094 of compound 167 (a Merck CCR5 inhibitor), combined with BMS 387806 (a CD4-blocking molecule from BMS), and c52L (a T-20 like fusion inhibitor molecule produced in engineered bacterial) were tested by Ron Veazey in macaques treated with progesterone to enhance their susceptibility to infection.<\/p>\n

8\/10, 6\/8, and 3\/5 monkeys were protected by each agent. 16\/20 given two agents, and all 3\/3 given all 3 agents were protected from high-dose HIV mucosal challenge. In a delayed challenge SHIV (a SIV-HIV hybrid) experiment, microbicides were 80% effective 30 minutes after application, but only 33% protective at 12 hrs. 2 of 5 animals were protected against 5 daily high-dose challenges by daily triple application.<\/p>\n

In addition to being effective, microbicides must be affordable. Moore estimated that a product could only cost $0.25-0.50\/application. This is a challenge as the amount of compound needed to be effective varied from as little as 3 mg\/application to 50 mg. Compounds must reach the millimolar range to protect in the monkey model, which is several-fold higher than in vitro models. In general, receptor blockers need to achieve higher concentrations than antivirals.<\/p>\n

In the real world, the challenges will be great. Viral load (innoculum) is likely to be high in many settings as transmission is associated with other active STDs. A product requiring daily application is unlikely to achieve perfect adherence. The cheapest candidates as polyanion detergent-like antivirals at <0.01$ dose, antiviral drugs come in at $0.01-0.10\/dose, and small peptides or molecules are the Rolls Royce at $1-20\/dose. An interesting idea that Moore mentioned was Dean Hamer\u0092s proposal to engineer live bacterial flora to secrete antivirals, a clever and interesting idea that would need proof of concept in a model system, and acceptance by the public.<\/p>\n

Reference:<\/p>\n

Moore J. Preventing HIV transmission by topical microbicides. Plenary lecture Wednesday 8 February, 13th CROI, 2006, Denver. Abstract 121. Webcast available on conference website.<\/p>\n

Source: www.natap.org<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

David Margolis, for natap.org Topical microbicides, preparations able to kill HIV on contact and prevent infection, are a critical complement to vaccines and other prevention strategies. They can protect women, for example, who cannot protect themselves by other means. Gels …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,10,42],"tags":[60],"class_list":["post-3299","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-transmission-and-prevention","category-vaccines-and-microbicides","tag-croi-2006"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3299","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=3299"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3299\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=3299"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=3299"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=3299"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}