$37M grant awarded to Imperial for HIV prevention study in Africa

An international research partnership involving the London School of Hygiene & Tropical Medicine (LSHTM) and Imperial College London has been awarded $37 million to test an innovative combination of strategies to prevent HIV in African countries.

The project, called PopART, will test the impact of a combination prevention strategy that combines community-wide house-to-house voluntary testing for HIV, offer of medical circumcision to men who test HIV-negative, and offer of immediate initiation of antiretroviral therapy (ART) for all those testing HIV-positive.

Researchers at Imperial and partners including LSHTM, the Zambia AIDS Related Tuberculosis Project (ZAMBART) and the Desmond Tutu TB Centre (DTTC), Stellenbosch University, South Africa will work closely on this trial with colleagues from the HIV Prevention Trials Network (HPTN).

Part of the HPTN, the study (designated HPTN 071) has been funded jointly by organisations including the National Institute of Allergy and Infectious Diseases (NIAID),the National Institute of Mental Health (NIMH), the Office of the United States Global AIDS Coordinator (OGAC) and the Bill and Melinda Gates Foundation (BMGF).

Starting in 2012, the trial will take place in 24 communities in Zambia and South Africa, with a total population of over 1 million. Eight communities will receive the full PopART intervention while eight control communities will receive current standard of care. The remaining eight communities will receive an intermediate intervention which includes all the components of PopART except that ART will be given according to current national guidelines. This three-arm design will allow the trial to measure the extra effect of treating patients immediately rather than waiting until their immune function has deteriorated. A total of 60,000 adults from the communities will be followed up for two years to measure the impact of the interventions on new HIV infections.

An estimated 33 million people worldwide are living with HIV. With 2.5 new infections for every HIV-positive patient commencing ART, current approaches to treatment and prevention are struggling to contain the spread of the infection.

Unless the incidence of HIV can be steeply reduced, forecasts predict that the number of HIV-infected individuals will continue to grow so that by 2030 about $35 billion per year will be needed to deliver ART to HIV-positive patients in these resource-limited settings. Combination prevention approaches like PopART may be initially more expensive than current approaches, but estimates suggest that if HIV incidence is not reduced significantly, the financial impact of an ever-increasing number of patients in need of treatment and hospitalisation will be far greater.

Mathematical modelling has shown that the PopART intervention should lead to a steep reduction in new HIV infections. A rigorously designed trial is now needed to test whether such interventions can be effectively implemented in resource-poor settings in Africa, and to measure the actual impact on HIV at population level. Professor Peter Smith, from the Imperial College Business School, will lead on evaluating the impact and cost-effectiveness of the trial.

Richard Hayes, Professor of Epidemiology and International Health at LSHTM and the principal investigator of the study, said: "PopART is designed as a universal intervention offered to the entire community. We hope this will prevent stigmatisation of infected individuals and reduce the need for specially targeted interventions for specific risk groups. There is a strong rationale for the PopART approach, but we need a rigorously conducted study to determine how well the strategy can be delivered in practice, and what impact it has at population level."

Dr Sarah Fidler, Senior Clinical Lecturer in HIV at Imperial, said; "The PopART trial is the first International study to test the feasibility and impact of delivering a combination HIV prevention approach, proposed by mathematical models to have the capacity to significantly reduce HIV incidence. This study will not only enhance the provision of life saving treatment for all those infected with HIV, consequently reducing the risk of onward viral transmission, but also incorporates additional strategies to limit risks of viral acquisition; potentially conferring both individual and population level benefit."

Christophe Fraser, Professor of Epidemiology at Imperial, said: "Offering HIV tests and immediate treatment, universally, may seem unaffordable in these austere times. But in the long run, and in combination with other prevention activities, this may be the best prevention measure available to stop people continuing to get infected with this lethal virus. This trial will test this proposition to the limit, and will hopefully she d some light on how the AIDS epidemic can sent into reverse."

The new project builds on two previous HPTN trials. Project Accept (HPTN 043) found that adding community mobilisation and support services to a mobile HIV counselling and testing programme can improve rates of testing in rural communities. HPTN 052 was the first randomised trial to show that treating an HIV-infected individual with ART reduces the risk of sexual transmission of HIV to an uninfected partner.

The first PopART concept followed the completion of a large international trial, called SPARTAC, led by Professor Jonathan Weber from the Department of Medicine at Imperial. SPARTAC looked at whether there are any benefits to giving an early short course ART in individuals recently infected with HIV. The results are due to be published in the near future. An extension of this idea to a population level effect of universal HIV test and treat was further explored by Professor Weber and his group and has led to the development of this next programme.