IAS: Prevention is the new 'treatment'

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For the first time in over a decade, a major scientific HIV conference was not dominated by news and debate on HIV treatments or access to them, but on HIV prevention.

There were several reasons for this. Firstly, the IAS decided to make prevention science a separate and equal strand in the oral and poster presentations. Studies of everything from novel microbicides in animal models to the ‘underground’ use of pre-exposure Prophylaxis in US gay men (see separate feature on PREP) gained as much attention as the ones about new drugs and treatment strategies.

Secondly, the biggest single news story of the conference was the French INSERM randomised controlled study of male circumcision, which was found to reduce HIV incidence in men by 65 to 75 per cent (see separate news story).

Glossary

voluntary male medical circumcision (VMMC)

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

circumcision

The surgical removal of the foreskin of the penis (the retractable fold of tissue that covers the head of the penis) to reduce the risk of HIV infection in men.

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.

efficacy

How well something works (in a research study). See also ‘effectiveness’.

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

Thirdly, there was an appreciation that without a renewed concentration on HIV prevention, the current scale-up in antiretroviral provision will only result in greater HIV prevalence, as it has already done in the developed world.

UNAIDS Director Peter Piot, in his closing speech, said that only 10 per cent of men who have sex with men and five per cent of injecting drug users worldwide have access to HIV prevention tools. He said that while he welcomed the recent G8 Summit’s call for universal HIV treatment by 2010, he was “puzzled, disappointed, even angry” that they had not also called for universal access to prevention by that date.

In a forum on the conference’s first afternoon, Marie Laga of the Institute of Tropical Medicine in Antwerp provided some sobering forecasts of the impact of universal treatment on HIV prevalence.

She said that a meta-analysis of 21 studies of the short-term effect of treatment on sexual behaviour found overall a neutral or slightly negative effect on unsafe sex.

But she added that in the longer term mathematical models predicted that in the absence of renewed prevention efforts it would take a less than 10 per cent increase in unprotected sex to out-balance the estimated decline in a fully-treated population’s average infectivity. Even the most optimal treatment programme, if prevention was abandoned, would result in a 33 per cent increase in AIDS deaths worldwide by 2019.

In contrast, a prevention-only strategy would see the same number dying of AIDS in 2019 as now (after an initial rise), and the best possible combination of treatment and prevention might bring AIDS deaths down by about 25 per cent by then.

In a presentation on the following day, Ward Cates of Family Health International stressed the difference between the efficacy of prevention methods, as measured under ideal trial conditions, with their effectiveness in real-world situations.

Using condoms as an example, he said that the rate of HIV seroconversion among HIV-discordant couples who ‘always’ used condoms was about 0.5% a year. But the rate among couples who 'sometimes’ used them was 5.1% a year – not much less than the 6.5% for those who never used them.

He calculated that the proportion of HIV-negative people infected after a decade of perfect use of condoms with positive partners would be just five per cent. With microbicides, because of their predicted lower efficacy, it would be 40 per cent.

However after a decade of more realistic typical use of either of these interventions, 70 to 75 per cent of partners would be infected.

In contrast, with interventions that required a one-off medical intervention and were not subject to continued adherence, there was almost no difference between ‘perfect’ and ‘typical’ use. Such interventions could include an HIV vaccine and also, of immediate relevance given the news, male circumcision.

Cates called for a greater emphasis on early detection of HIV. In concentrated epidemics, he said, intensive contact-tracing using PCR detection methods that could pick up infections before seroconversion was one way to break the chain of infection.

In generalised epidemics, given that concurrence of sexual relationships was at least as important as the absolute number of them, an emphasis should be laid on the ‘Be faithful’ strategy as the lead one.

Cates added that because of low adherence rates among participants, political controversy such as with the tenofovir PREP trials, and drop-outs in women who became pregnant during microbicide trials, at least 90,000 participants would be needed for non-vaccine prevention trials before 2010, with only 30,000 currently enrolled.

Bernard Schwarzländer of the World Health Organisation (WHO) also laid emphasis on the practical and ethical difficulties of HIV prevention trials.

He listed five major dilemmas:

  • Human resources. Who do we decide to put in a trial, given that their participation may rule them out of a later trial of a better intervention, or even (as with a proposed trial to use single-dose tenofovir instead of nevirapine to prevent mother-to-baby transmission) possibly not work as well as the current one?
  • Prevention trials are sometimes guided by political and religious belief. For instance, we simply don’t know the contribution of condom use to the decline of HIV prevalence in Uganda. Trials of ways to increase condom use – or trials of alternatives to condoms such as abstinence – may neglect an effective intervention while making a marginal difference to a less effective one.
  • Stigma: what responsibility do we have for the negative effects on people who are found to be HIV-positive when screened for a trial?
  • Treatment: the advent of ARV treatment has made this dilemma worse; trials have been stopped because they are not funded to treat people testing positive at the screening stage. Researchers must negotiate with governments and NGOs to fund treatment before trials start.
  • What do we do with interventions that only benefit some of the population? For instance, circumcision will probably only benefit HIV-negative heterosexual males. What if the net effect is sexual disinhibition in those men? Will circumcision not be offered to HIV-positive men, or will they start getting circumcised to ‘look safe’?

Nonetheless, he added, “with five million new infections a year, we should be prepared to skate on thin ice and take some risks.”