Prevention – there will be no magic bullet, we need ‘combination prevention’

Roger Pebody, Gus Cairns
Published: 06 August 2008

Whether described as “combination prevention” or “highly active HIV prevention”, the emphasis at the International AIDS Conference in Mexico City has been on the need for multi-pronged prevention programmes. This was especially the case at a special session convened by The Lancet on August 5th, where some of the world’s leading researchers called for HIV prevention efforts to be redoubled, in a manner equivalent to the campaign to provide universal access to HIV treatment.

Jeff O’Malley of the United Nations Development Programme said that the history of HIV prevention had been a history of failed single solutions. Even if many speakers were optimistic that a successful microbicide or pre-exposure prophylaxis product will be developed, they said that new prevention technologies like these will not make behaviour change work obsolete, just require it to be more sophisticated.

Thomas Coates of the University of California said that relying on one or two prevention strategies was like using ineffective monotherapy to treat HIV.

He argued that each prevention success to date has resulted from “a complex combination of strategies and several risk-reduction options with strong leadership and community engagement that is sustained over a long time.”

Prevention would therefore require:

  • Behavioural change such as reducing concurrent relationships and using condoms
  • Biomedical strategies such as circumcision and the prevention of mother-to-child transmission
  • Treatment of HIV, other viruses and sexually transmitted infections
  • Social justice and human rights.

Prevention successes have usually involved early efforts by community activists to confront the stigma and denial associated with HIV, and subsequent strong political leadership. Speakers made it clear that proven behaviour change interventions and new prevention technologies will only have a limited impact if they are carried out in settings without social justice and human rights.

This was not the first time that there has been a call for HIV prevention to address factors such as poverty, gender and social marginalisation. However Jessica Ogden from the International Center for Research on Women in Washington DC said that such an emphasis was long overdue if there is to be a shift from dealing with HIV as a short-term emergency to taking a long-term response.

However she acknowledged that incorporating such approaches into HIV prevention has challenges. The relationship between a structural factor and HIV risk behaviour is complex and hard to define. Moreover, social change is not a top-down, pre-planned process but is something dynamic and unpredictable that involves many actors and cannot usually be transferred from one setting to another.

Nancy Padian of the Women’s Global Health Imperative reviewed the range of biomedical interventions available to block HIV infection. She discarded the historic classification of interventions in terms of their mode of delivery, and instead brought together all those interventions which rely on the use of antiretroviral drugs, which has the benefit of highlighting the fact that many of the proven and some of the most promising interventions have this point in common.

The use of antiretrovirals to prevent mother-to-child transmission and in post-exposure prophylaxis is already well demonstrated, and the effect of antiretrovirals on the infectiousness of people with HIV was the subject of numerous conference debates. Moreover, there is considerable hope that “oral antiretrovirals” will be effective as pre-exposure prophylaxis (PrEP). In addition, after disappointing results with other products, the most promising microbicide candidates use antiretrovirals and are now sometimes referred to as “topical antiretroviral preparations”.

She also highlighted the need for adherence to use of biomedical strategies, and contrasted those for which only a single or limited number of decisions would be needed (circumcision, vaccine) with those which require daily adherence (treatment of sexually transmitted infections, oral antiretrovirals, topical antiretrovirals). The greatest challenges for adherence involve techniques such as male condoms which require adherence around the time of sex.

On the topic of behaviour change, Thomas Coates warned prevention researchers not to attempt to reduce sex “to an antiseptic act described in acronyms – UIAI and so on.” Human beings engaged in sex “for a variety of motives - for procreation, for fun, for money or because they don’t have a choice,” and HIV prevention required not small, but radical change in this most complex of activities.

He was also not the only speaker to criticise the assumption that HIV prevention could be treated like HIV medicine in that strategies had to be tested in randomised controlled trials before being adopted. “We have become slaves to the RCT and matched the intervention to the science,” Coates said. “We have to start matching the science to the intervention.”

Stefano Bertozzi, Director of Economics at the National Institutes of Health, said that HIV prevention has not reversed the course of the epidemic for three reasons:

  • The available interventions were not sufficiently effective
  • There was not enough funding for prevention
  • Funding was often wasted due to poor implementation of the available interventions.

Bertozzi talked mainly about the third point. He said that money was wasted in prevention for two reasons. Firstly, funding was poured into interventions whose efficacy was not then properly evaluated. He said that too often “we have done, without learning by doing.” An element of operational research had to be built into every prevention programme and programmes had to have the capacity to be iteratively changed if they were not reaching people of the right age, with the right risk profile, or in the right location.

He also said that money was directly wasted through high costs, poor quality and low coverage in many programmes. He showed a graph which revealed that, in general, the cost-per-test of voluntary counselling and testing had declined over the last few years as more patients were tested, due to economies of scale. However in some countries such as India the improvement in efficiency had been consistent, while in others including Russia and Mexico there were enormous disparities – amounting to several orders of magnitude – between the cost per person tested in different programmes. He said that in future, prevention funding should be tied to performance and a business model should be adhered to: “You can’t imagine McDonald’s not knowing how many hamburgers they’ve sold; but in prevention all we do is hand out money.”

He urged the adoption of private-public partnerships in prevention, as in the case of India, where HIV prevention was shared out between national and state-funded programmes and the Avahan Institute, a Gates Foundation-funded prevention initiative that in some states runs the majority of programmes. Avahan has recruited staff from the private sector and uses business models to ensure that prevention methods are consistently being targeted at the most at-risk populations.

Peter Piot, Executive Director of UNAIDS, also singled out the Avahan project for praise. He agreed with Tom Coates that HIV prevention was about “generating systemic social change” and with all the other speakers that ‘magic bullet’ thinking should be a thing of the past in HIV prevention. “HIV prevention based upon just one or two strategies in isolation may actually be counterproductive,” he commented.

He called, as he has done many times before, for “sustained political and technical leadership” in HIV prevention and “political courage on sexuality, gender, drug use and harm reduction.” However he also called on HIV activists to get behind prevention, citing as a good example the Treatment Action Campaign in South Africa who, despite their name, had campaigned vigorously for sex education and condoms in schools. He asked the HIV activist community to assist in the development of “a cadre of competent community prevention workers.”

Piot’s point about political courage was ironically remade at the end of the session when a sex worker activist took over the microphone and demanded to know why UNAIDS had not provided leadership and guidance on prevention programmes for sex workers. Clearly, effective HIV prevention relies on finding solutions to a dizzyingly interlinked set of scientific, sociological, structural and political problems, but there are enough positive models out there to know that they can be solved.

Reference

The Lancet Series on HIV Prevention. XVII International AIDS Conference, Mexico City, August 5 2008. TUSS02.

Comprehensive analyses of the HIV prevention field, written by those presenting at the session and others, were published in The Lancet during August and September 2008:

Horton R and Das P. Putting prevention at the forefront of HIV/AIDS. The Lancet 2008; 372:421-422

Wilson D and Halperin DT. “Know your epidemic, know your response”: a useful approach, if we get it right. The Lancet 2008; 372:423-426

Merson MH, O'Malley J et al. The history and challenge of HIV prevention. The Lancet 2008; 372:475-488

Padian NS et al. Biomedical interventions to prevent HIV infection: evidence, challenges, and way forward. The Lancet 2008; 372:585-599

Coates TJ et al. Behavioural strategies to reduce HIV transmission: how to make them work better. The Lancet 2008; 372:669-684

Rao Gupta G, Ogden J et al. Structural approaches to HIV prevention. The Lancet 2008; 372:764-775

Bertozzi SM et al. Making HIV prevention programmes work. The Lancet 2008; 372:831-844

Piot P et al. Coming to terms with complexity: a call to action for HIV prevention. The Lancet 2008; 372:845-859.