A new four-year, $20 million grant from the U.S. Centers for Disease Control and Prevention (CDC) will enable Harvard School of Public Health (HSPH) researchers to evaluate the impact and cost-effectiveness of a unique combination of HIV prevention strategies in Botswana.

The CDC grant is part of a U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) initiative that commits $45 million to examine the effectiveness of combination approaches to HIV prevention over four years. The largest evaluation of its kind, the HSPH research initiative is poised to help partner countries strengthen their efforts to prevent new HIV infections and save lives.

Principal investigator Max Essex, professor of health sciences and chair of the Harvard School of Public Health AIDS Initiative, and co-principal investigator Victor De Gruttola, professor of biostatistics and chair of the Department of Biostatistics at HSPH, predict that their prevention strategies can reduce HIV infection by at least 50 percent.

Notably, one aspect of the study includes a focused effort to prevent HIV transmission by individuals with a high viral load. “This is the subset of people most likely to transmit the virus,” said Essex.

He and his colleagues believe that targeting those most likely to transmit HIV can greatly reduce disease incidence and be cost-effective. Essex noted that some researchers have advocated supplying all HIV-positive individuals in a particular group with antiretrovirals, but covering all infected people in populations with high rates of infection can be prohibitively expensive for governments in developing countries.

Another unique aspect of the HSPH study is that researchers will study viral gene signatures (the genomic fingerprint of a virus) to determine the effectiveness of targeting individuals with high viral loads. Using this method can indicate whether new infections originated within a particular village, for example. Identifying viral gene signatures could also determine how much the study interventions are able to reduce infections that can be traced to individuals with high viral loads.

Researchers will also analyze cost savings realized from using the prevention strategies in the study. “The hope is that the strategies will help countries cut costs dramatically,” said Essex. “Conducting a study of this type in southern Africa is more logical because HIV infection rates are much higher than those in the U.S., and the results can be obtained sooner.”

The study will be conducted in collaboration with the Botswana Harvard AIDS Institute Partnership (BHP), a 15-year-old collaborative research and training initiative between the Harvard School of Public Health AIDS Initiative and the Botswana Ministry of Health.

Despite of Botswana’s significant efforts to curtail the incidence of HIV/AIDS, 25 percent of adults in this southern African country are HIV-positive. To home in on ways to optimize HIV prevention strategies, HSPH and BHP researchers will conduct a randomized study of nearly 50,000 people — 22,000 in the village of Mochudi, and roughly 28,000 in 16 rural communities. HSPH and BHP researchers, working with Botswana’s Ministry of Health, will examine the effects of combining a number of prevention strategies over a four-year period. In addition to treating high viral load, the interventions include the following:

• Testing and counseling more than 70 percent of 18- to 49-year-old adults

• Voluntary circumcision of more than 70 percent of 18- to 49-year-old adult males not infected with HIV

• Providing more than 90 percent of HIV-infected adults with antiretroviral therapy

• Providing antiretrovirals to 95 percent of HIV-infected pregnant women in order to prevent disease transmission to their children

These interventions have not been adequately evaluated in combination, said Essex. Using a number of prevention strategies together at the same time should also test whether they have a synergistic effect. According to co-principal investigator De Gruttola, “Studying people as members of village communities rather than as isolated subjects allows for mathematical modeling of the effects of combination prevention strategies in the settings in which they will actually be used.”

Starting out green