What is up with Nonoxynol-9? Global Campaign for Microbicides

Background on Nonoxynol-9 Nonoxynol-9 is the active ingredient in most over the counter spermicides 'Film 70 mg 'Foams mg 'Suppositories 100 mg 'Gels mg 'Sponge1000 mg

N-9 also added to Some over-the-counter sexual lubricants KY Plus (with N-9)2% by volume ForPlay  (with N-9)1% by volume Some lubricated condoms mg (US) mg (outside US)

History of N-9 testing Early testing proceeded in the hope that an existing product might prove effective against HIV Previous human studies suggested that it offered some protection against gonorrhea, chlamydia, & HIV (based on epidemiological studies not RCTs) Early clinical trials done with different products in different populations showed contradictory results  some suggested that N-9 could increase HIV risk  some suggested that low dose products could decrease risk So work on lower dose N-9 products continued

UNAIDS trial reveals no protection for Advantage-S Preliminary data out of Durban in July, showed that sex workers using Advantage-S gel (52.5 mg of N-9) had higher rates of HIV sero-conversion than those using placebo, 3possibly due to increased vaginal disruption caused by the N-9 These data are difficult to generalize because of the variation in dose and formulation among various N-9 products Sex workers had on average 3.7 clients per day

Nonoxynol-9 and rectal sex David Phillips et al found that even low doses of N-9 caused massive sloughing of the rectal epithelium (n=4 people). Findings duplicated in large sample Rectal epithelium heals quickly – less than 8 hours Damage associated with rectal use of N-9 is far more extensive than observed with vaginal use of products Rectal exposure to N-9 increases transmission of HSV in mice and monkeys

Who is at risk? In US, more women than men have receptive anal sex % of heterosexual women in the US had anal sex in the last year (Gross et al, 2000) In one US study, 32% of high-risk women participants reported anal sex in past six months (Gross et al 2000) In a Chinese study of 1300 people from 41 cities, nearly 70% of men and women reported engaging in anal intercourse (Burton 1990).

What happened next? Work with N-9 as a potential microbicide ceased CDC issued guidance saying that N-9 should not be recommended for HIV prevention or included in “hierarchical” messages and N-9 lubricated condoms should no longer be recommended WHO held an expert consultation in October 2001 to further refine public health messages around N- 9 and N-9 lubricated condoms

WHO Expert Group Findings N-9 does not provide protection against HIV or bacterial STDs such as gonorrhea and chlamydia. When used frequently in the vagina (more than once a day*), N-9 products cause epithelial disruption that may increase the risk of HIV infection. Women who are at risk of HIV or have multiple acts of intercourse in a day should use a different form of contraception. Spermicides containing N-9 remain a safe contraceptive option for women who are not at risk of HIV

Findings (continued) Under no circumstances, should N-9 containing products be used rectally. There is no evidence that condoms lubricated with N-9 are more effective in preventing pregnancy or infection when used vaginally than condoms lubricated with silicone. Therefore N-9 condoms should no longer be promoted. (Nonetheless, a condom with N-9 is still better than no condom at all)

Public Health Challenges The idea that N-9 offers “extra protection” from HIV is very entrenched Big confusion regarding N-9 products and messages Complicated message to impart: 3N-9 does not work for STD/HIV prevention 3Should NOT be used rectally – may increase risk 3Safe to use vaginally for pregnancy prevention if you are not at risk of HIV and use infrequently

Gay men are still seeking out N-9 Among a diverse sample of 573 MSM in San Francisco, 67% had used N-9 in the past year This was after CDC issued warnings and the San Francisco DOH undertook outreach activities Among those who had used N-9 in the last year: 3 41% used it without a condom because they thought the N-9 might be protective 3 74% used it with a condom for “added protection”

Origins of N-9 Call Global Campaign for Microbicides responded because data on rectal use of N-9 isn’t being heard Formed partnership with GAAN to develop strategy to reduce risks due to rectal exposure to N-9 Simultaneous goal to build stronger partnerships with gay/lesbian and mainstream AIDS groups around need for rectal microbicide research Created working group of scientists and representatives of key constituent groups to develop strategy

Consensus message New data reveal that when used rectally, even small doses of nonoxynol-9 can increase risk of HIV transmission When used consistently and correctly, lubricated condoms give excellent protection against pregnancy and HIV, even without the addition of Nonoxynol-9.; Adding N-9 to condom lubrication may not provide any additional protection against pregnancy Therefore, we are asking manufacturers to help eliminate this public health risk by phasing out the addition of N-9 to condoms and sexual lubricants

Logic behind Call Two pronged strategy for change: 3public education to “undo” entrenched messages re: N-9 3phasing out source of risk by removing N-9 from products used rectally N-9 in lubricant benefits no one, therefore it should be phased out N-9 on condoms can harm those using it rectally. It has no proven benefit in terms of birth control. Therefore, it should be eliminated. N-9 contraceptive products are the only user-controlled, non-hormonal birth control methods available in the US. Women need this option. They also need education about its benefits and risks.

Global Campaign Response Conversations with manufacturers Call to Discontinue Use Letter to FDA re: labeling etc. Efforts to pressure CDC to fund major education effort (via consortium of groups like NFPRHA, ASHA, etc). Follow up efforts re: safety testing of existing lubricants Coalition building for microbicides

What does this mean for microbicides in general? Recent news about N-9 has led some people to think that developing a safe, effective microbicide is impossible. This isn't true! The N-9 research data don’t suggest that a developing safe and effective microbicides is impossible -- only that N-9 probably is not one of them.