Rectal HIV microbicides still a distant prospect

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A seminar held last Sunday in London ahead of the Microbicides 2004 meeting reviewed progress towards rectal microbicides, products to prevent HIV transmission through anal sex. The meeting was organised by the University of California, Los Angeles AIDS Institute, with participants from Europe, North America and South Africa, some of whose findings were also presented at the main meeting.

A session on behavioural research focused on the need for microbicides that can be used rectally. This need is clearest for gay men, for many of whom anal sex is a highly valued activity, although greater absolute numbers of heterosexuals engage in anal sex at some time or other.

In North America, incidence of HIV among gay men continues to be around 2% per year, most of which is still due to unprotected anal sex. Community surveys and rates of sexually transmitted infections in a number of countries have repeatedly shown how difficult it is to maintain high rates of condom use. A significant minority of gay men have never really taken to condom use. There are strong tendencies for condoms not to be used in steady relationships, even when the HIV status of the two partners is unknown.

Glossary

microbicide

A product (such as a gel or cream) that is being tested in HIV prevention research. It could be applied topically to genital surfaces to prevent or reduce the transmission of HIV during sexual intercourse. Microbicides might also take other forms, including films, suppositories, and slow-releasing sponges or vaginal rings.

rectum

The last part of the large intestine just above the anus.

stigma

Social attitudes that suggest that having a particular illness or being in a particular situation is something to be ashamed of. Stigma can be questioned and challenged.

douching

Using water, soapsuds or another liquid to cleanse the vagina or rectum before sex.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

An American focus-group study of gay men in Baltimore, presented at the satellite meeting by Dr Craig Hendrix, explored the use of lubricants, douching practices, and attitudes towards a possible rectal microbicide (Hylton).

Lubricants are widely used for anal sex even when condoms are not, usually applied by hand to both penis and anus. Water-based lubricants are re-applied at intervals, approximately every five minutes, although oil-based ones (which should not be used with latex condoms) tend not to be re-applied.

The use of enemas prior to anal sex remains common, usually with tap water, to which other substances may be added, which may diminish a limited protective effect from bacteria present in the digestive system. This could be a way to deliver a microbicide, but one that would suit some men (for example, those who have sex in their own homes) far better than others.

Another study by Dr Hendrix recruited male volunteers who simulated intercourse using plastic dildos they inserted in their own anus, to find out what happened to either a semen surrogate or a pretend microbicide gel, during and after “sex." The “semen" was a diluted lubricant gel labelled so it could be viewed with an MRI scan. Inert chemical particles matching HIV for size were added, which could be viewed in another scanning system called SPECT. The researcher inserted the “semen" from a syringe through a tube in the dildo and scans were then made up to five hours after its release. The key finding of this study was that, on at least some occasions, the “semen" could travel up to 60 centimetres along the gut, reaching as high as the splenic fold. This highlighted, very literally, the challenge of getting a microbicide to where it was needed and getting it to stay there long enough to protect the extremely vulnerable tissues of the gut surface. Perhaps only an enema, or a drug taken orally, could realistically do this.

An alternative view was advanced by Dr Ross Cranston of UCLA in a presentation on the anal canal and rectum, where physical contact can be made with tissues subject to possible co-infections with herpes (causing ulcers) and human papilloma virus (leading to hidden warts), plus conditions such as hemorrhoids. All these conditions can lead to breaches in the mucosa and direct exposure of activated T-cells and dendritic cells to HIV in semen. If most HIV transmission through anal sex is happening in a relatively small region, then anything done to protect it could substantially reduce that risk.

However, Dr Hendrix’s studies of a potential microbicides had shown that very little was retained in this region, most of it went higher up in the colon and beyond.

Among the six microbicide candidates now poised for Phase III trials, only one, the nonoxynol-9-like Savvy (also known as C31G), is clearly unsafe for rectal use. However, none of the others are thought likely to be effective used rectally: newer microbicides based on antiretroviral drugs are the best prospects. Seminar participants were unsure how realistic it is to expect separate formulations of microbicides to be made and tested for rectal use. Trials could, however, be much smaller among US gay men than among heterosexuals, as shown by the recent VaxGen trials for the unsuccessful AIDSVAX HIV vaccine.

While some populations of women who report experience of anal sex may be at higher risk of HIV, it is still far from clear how much this contributes to HIV transmission. In North America, the picture is complicated by associations between reported anal sex, injecting drug use, participation in group sex, and sex for payment. There are suggestions that Latina women are more likely to report anal sex, and that Latino men are more likely to report bisexual behaviour than members of other communities in the USA. However, there is a need for more detailed research to identify situations, relationships and populations where anal sex occurs, before the potential value and opportunity for use of any means of protection can be discussed.

Heterosexual anal sex is highly stigmatised in many cultures, hindering research, although questions are being asked in Brazil, India, other Asian and several African countries, especially where clinical trials of vaginal microbicides are planned. So far, however, it appears to be an occasional practice for most people, and unlikely to invalidate vaginal microbicide research.

References

Hendrix CW et al. Imaging the distribution of a rectal microbicide gel and semen surrogate in the lower GI tract. Microbicides 2004, London, oral abstract 02685.

Hylton J et al. An assessment of sexual practices affecting the feasibility of microbicide development among MSM. Microbicides 2004, London, poster 02667.