Un update on prevention technologies from the IAS conference, by Rob Dawson

Condom promotion and distribution is a key focus in HIV prevention and where they are accessible and acceptable there is no doubt about their effectiveness. However, just as HIV treatment evolves and improves to take into account an individual’s needs, so too must prevention strategies. Condoms alone are not the answer for everyone, and with such a diverse range of populations affected by HIV, increasing our arsenal of prevention tools could provide a more effective approach.

Several presentations at the recent International AIDS Society (IAS) conference in Sydney helped to advance our understanding of how combining new prevention technologies could enhance condom use, rather than replace it.

Cutting infections

One prevention tool that has received much recent publicity is male circumcision. While studies have found that male circumcision could reduce female-to-male transmission of HIV by around 60%¹, there was debate in Sydney as to whether roll-out of mass circumcision programmes would be effective and feasible.

Circumcision researcher Bertran Auvert and colleagues in France, South Africa and the United States developed a costing model to address some of the issues. They used demographic data from 14 African countries where the prevalence of circumcision was less than 80% and adult HIV prevalence was more than 5% and modelled the cost for individuals and the public sector of a rapid roll-out of circumcision for adult males. They found that the circumcision as an HIV prevention measure would need to have high uptake and substantial funding in the first few years if it is eventually to be cost-effective.² Dr Auvert calculated that you would need to circumcise between four and nine men to prevent each new HIV infection but he believes that, while this would be expensive, it would ultimately be worthwhile given the long-term savings in treatment and care.

Separate modelling data were also used to show that targeting only 20 to 30 year-old men or men with a greater number of sexual partners may produce the most cost-effective reduction in HIV prevalence.³  

While there has been concern that circumcision programmes may encourage those men that have had the surgery to take more sexual risks, there are data to suggest that this may not be the case. Professor Robert Bailey of University of Illinois, Chicago, School of Public Health, speaking during a plenary session at the conference, pointed out that in his study, risk behaviours by circumcised men fell during the twelve months that followed the surgery.¹

Circumcision may be beneficial for some, but there are cultural and social barriers which mean that there is no guarantee that it can be applied. Finding appropriate high-risk groups is key. Bailey noted that general circumcision programmes outside of Africa may not be appropriate or effective but that targeted programmes for high-risk heterosexual men should be explored.

While one study at the IAS conference showed that gay men are willing to be circumcised, another showed that it is unlikely to be an effective form of HIV prevention in this setting.

Dr Juan Guanira, of the Asociación Civil Impacta Salud y Educación, Peru, reported that South American men who had sex with men (MSM) would be willing to participate in a circumcision trial.⁴ However, there were concerns; men worried about undergoing surgery (62%), side-effects of surgery (72%), and encountering partners who would insist on having sex without a condom (75%).

While Dr Guanira argued that his data lay the foundations for a circumcision trial in MSM in the Andean Region, a different study had less promising results for men in Sydney. David Templeton of the National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, found that circumcised and uncircumcised gay men had the same risk of becoming infected with HIV.⁵

He explained that most HIV infections in homosexual men occur after receptive anal sex, and so circumcision is unlikely to be an effective HIV prevention intervention for Australian gay men. However, he felt that further research is warranted into populations where gay men are more likely to be exclusively receptive or insertive in their sexual roles.

Pre-prepared

The idea that antiretroviral drugs could play a preventative role if taken prior to any risk of HIV infection is not a new one, but developments in this area take time. Pre-exposure prophylaxis (or PrEP as its known) may have great potential in reducing HIV transmission but determining how they could be best used, if proven effective, needs careful consideration.

With results from the first PrEP clinical trials expected early next year, an IAS Industry Liaison Forum addressed some of the challenges that could be faced. The key areas needing focus in the coming months were defining priorities for PrEP’s use and using modelling techniques to help determine what impact it might have on different population.

Dr Dawn Smith, a medical epidemiologist at the US Centers for Disease Control and Prevention, highlighted the importance of acting now, before the trial data is ready, by surveying stakeholders and potential participants so that they can truly understand how to implement PrEP effectively.

On novel use of PrEP, presented by Pietro Vernazza of St Gallen Cantonal Hospital, Switzerland, was as a safeguard for serodiscordant couples who wanted to try natural conception. This small Swiss suggested that HIV-negative women may be able to conceive safely by having timed unprotected intercourse with their HIV-positive male partner – as long as the partner’s seminal viral load is undetectable.

 A combination of couples counselling, STI screening, timed intercourse and a “psychological safeguard” of two doses of tenofovir (Viread) as PrEP had resulted in a pregnancy rate of over 70%, and no HIV transmission.⁶

Dr Vernazza told the conference that with a suppressed viral load in semen the risk of HIV transmission “is getting towards zero.” He considered PrEP to be an additional risk-lowering intervention but felt that it was primarily used as a “psychological safeguard” to ease concerns.

Microbicides

New products in microbicide research and development pipeline were discussed by Zeda Rosenberg, Chief Executive Officer of the International Partnership for Microbicides. She made the important distinction between first generation products, which block HIV’s interaction with host cells, act over shorter time spans and require application just before sex, and second generation products, which use current antiretorviral agents, may act over a longer time span and allow for different dosing regimens. Her opinion was that long-acting, sustained-release delivery types, such as vaginal rings, are likely to be most useful. These would deliver locally high drug levels at the site of transmission, while levels in the rest of the body remain low. Their success depends on delivery of the right drug (to ensure potency and safety) at the right time and on studies to determine the levels of drug present.

She concluded that combinations of products are under development, with potential blocking multiple transmission pathways, but that increased toxicity and the difficulties of co-formulation must be considered.

Ian McGowan, Co-Director, Center for HIV & Digestive Diseases, David Geffen School of Medicine at UCLA , showed that the need for rectal microbicides is demonstrated not only by the established risk of unprotected anal intercourse among MSM but by epidemiological evidence showing high levels of anal intercourse among heterosexual populations in some countries. He recommended that rectal safety should be incorporated into the development of new vaginal products, given the likelihood of anal use, as well as expressing the need for specific rectal formulations.

Uncertain times

With so many questions surrounding these new prevention technologies, the need for further research is clear. But when we have male condoms that prove more effective, is our focus correctly placed?

By far the most important application for these technologies will be for situations were insisting upon male condom use is difficult – whether that’s due to cultural unacceptability or fear within relationships – but that’s not the sole benefit. Prevention clinical trials occur within the context of counselling, sexual health information and condoms and so if there is reduced incidence of HIV in the control arm (where no new technologies are being used) we could be determining important information about various methods of reducing transmission.

Where these new developments are promoted correctly, as part of a larger prevention package, it could be a case of two (or three) being better than one.

References

1. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet  369: 643-656, 2007.
2. Auvert B et al. Cost of the roll-out of male circumcision in sub-Saharan Africa. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEAC105, Sydney, 2007.
3. Londish B et al. Mathematical modelling of male circumcision in sub-Saharan Africa predicts significant reduction in adult HIV prevalence even when it is limited to certain age groups. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEAC104, Sydney, 2007.
4. Guanaria J et al. How willing are gay men to “cut off” the epidemic? Circumcision among MSM in the Andean region. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEAC102, Sydney, 2007.
5. Temptleton DJ et al. Circumcision status and risk of HIV seroconversion in the HIM cohort of homosexually active men in Sydney. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEAC103, Sydney, 2007.
6. Vernazza P, Brenner I, Graf I. Pre-exposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child. Fourth IAS Conference on HIV Pathogenesis, Treatment and Prevention, abstract MoPDC01, Sydney, 2007.