Three mathematical models presented at the Eighteenth International AIDS Conference in Vienna have found that circumcision and a microbicide, used separately or together, could produce modest reductions in HIV incidence.
The models, by Andrew Cox of the London School of Hygiene and Tropical Medicine and Hiam Chemaitelly of Weill Cornell Medical College in Qatar, broadly agreed that a realistic level of microbicide and circumcision adoption would produce an approximately 20% reduction in new HIV infections within 15 to 20 years. Adding comprehensive antiretroviral therapy (ART) into this mix would reduce new infections considerably more.
A third model, by Geoffrey Garnett of Imperial College in London, was cited by Bill Gates in his conference talk on Monday. This showed that adding in microbicides and pre-exposure prophylaxis (PrEP) to currently available prevention interventions – excluding ART – would reduce HIV infections by an additional 15 to 18%.
Andrew Cox’s model used as its baseline the current situation in Uganda and forecast changes for the next 15 years.
He initially assumed a rise in the proportion of men in the population who were circumcised would rise from 18%, as it is now, to 48% over the next ten years, and then stay the same. He assumed that circumcision stopped six out of ten infections in men. For microbicides, he initially assumed an efficacy of 60% (rather on the high side for the microbicide in the CAPRISA study) , that women would use them 80% of the time when they had them, and that they would be available to 30% of the population after ten years.
Under these circumstances, circumcision (if provided alone) would produce a 12% decline in new infections in the whole population and microbicides alone an 8.4% reduction, but they would produce a nearly 20% reduction if used together.
Various combinations of microbicide and circumcision would produce a 20% reduction, but one combination cited by Cox was 53% circumcision coverage combined with 35% microbicide coverage – both higher than his initial assumptions. A 40% reduction in incidence would require probably unrealistic coverage rates of 81% for circumcision and 63% for microbicides, and a 30% reduction in incidence would require 68% coverage of circumcision and 46% coverage of microbicides use.
Inevitably, circumcision would benefit men more and microbicides would be of greater benefit to women. If circumcision was the only intervention used, 70% of the reduction in infections seen would be amongst men and if microbicides alone were used, 65% of the reduction would be in women, but if used together, the sexes would share the benefit equally.
Hiam Chemaitelly looked at the effect of circumcision in serodiscordant couples and weighed it up against the impact of treating the HIV-positive partner; treating the negative partner (as PrEP); and 100% condom use. Her model did not include microbicides as it was developed before the CAPRISA result came out, but she commented that a microbicide appeared about as effective as male circumcision.
She based her modelling on an existing cohort of 1003 serodiscordant couples who are enrolled in a study in the town of Bushenyi in south-west Uganda.
Amongst the parameters used in a complex model were: a circumcision efficacy of 58%; that, if supported by voluntary counselling and testing (VCT), condoms would be 80% effective and would be used 57% of the time; that PrEP would be 60% efficacious at stopping infections and that adherence to it would be 72.5%; and that antiretroviral treatment would be 92% efficacious and that adherence to it would be 80%.
Importantly, she assumed in her initial model that everyone who was eligible for a specific intervention would be offered it.
Under these circumstances, she found that antiretroviral therapy (ART) used alone would produce a 69% reduction in infections between the partners; condoms (with VCT) and PrEP would reduce new infections by 37%; and circumcision by 19%.
Greater efficacies would result from combining them, thus:
Condoms and ART, 82%
PrEP and ART, 82%
Circumcision and ART, 75%
Condoms and PrEP, 62%
Circumcision and PrEP, 50%
Circumcision and condoms, 49%.
Finally, if all four interventions were used together, the reduction in infections would be 92%.
Chemaitelly emphasised the importance of condoms being supported by VCT; if people used condoms without counselling and testing support, she found much lower rates of efficacy for them. Similarly, if the other three interventions were in short supply, reductions in infections would be much lower. Hr model also assumed universal provision of ART to the positive partner; if it was only provided to people with CD4s under 350 or 200, lower effectiveness rates resulted.
She pointed out that her model showed that there was no ‘magic bullet’ in prevention and that impressive reductions in the infection rate between couples was only achievable by using the range of interventions available in combination.
Presentations and related abstracts by Andrew Cox and Hiam Chemaitelly are available on the official conference website.
Cox A et al. Combination prevention to achieve significant reductions in HIV incidence: projections of the impact of microbicide and male circumcision interventions in rural Uganda. Eighteenth International AIDS Conference, Vienna, abstract WEAC0101, 2010.
Chemaitelly H et al. The impact of interventions on HIV transmission at the level of discordant partnerships. Eighteenth International AIDS Conference, Vienna, abstract WEAC0102, 2010.