IAVI supports a number of HIV research projects devised to inform the design and development of AIDS vaccines. Our continuing epidemiological and clinical studies, conducted in partnership with research centers around the world, cover everything from HIV prevalence in various populations to the cellular and molecular analysis of the immune system’s response to HIV infection.

One clinical study, named Protocol D and done in partnership with researchers in Rwanda, Kenya, Uganda and Zambia, characterized the clinical reference ranges of healthy adults in sub-Saharan Africa who might volunteer for future clinical trials. Before this study, the "normal" standards against which to measure blood constituents and other clinical markers to gauge the health of volunteers were typically derived from data collected in the West and applied to healthy African adults. But little data were available to support the validity of this practice. This landmark, multicenter study confirmed more comprehensively, and on a much larger scale, what concurrent research by the US Centers for Disease Control and Prevention and the US Military HIV Research Program found: that certain blood parameters of healthy Africans do differ from those of corresponding Western populations. It also established a set of reference ranges that may help improve the quality of medical research conducted in the region.

Ongoing epidemiological studies supported by IAVI include:

• Protocol B: An HIV incidence and volunteer retention study continues at research centers in Kenya, Uganda and South Africa. Every quarter, volunteers at high risk for HIV infection are counseled, tested for HIV and educated on HIV prevention. A subset of volunteers thought to be at the highest risk for HIV infection is counseled and tested monthly. Those who become HIV positive are referred to the IAVI-sponsored study Protocol C (see below), which assesses the immune response to HIV in the earliest stages of infection and assures that the volunteers receive quality health care

• HIV Discordant Couples Heterosexual Transmission Study: Conducted at research centers in Zambia and Rwanda, this study examines HIV transmission between heterosexual partners, one of whom is infected at the time of volunteering. Such consenting "HIV discordant" couples have—since 1986 in Kigali and 1994 in Lusaka—been followed quarterly (and now monthly) and provided specialized counseling that includes risk reduction and condom advocacy. IAVI support for this large cohort study began in 2004

• Protocol C: Conducted at research centers in Kenya, Rwanda, Zambia, Uganda and South Africa, this study seeks to characterize the early and acute stages of HIV infection, charting the evolution of both the virus and the immune system’s response to it from early infection onward. All volunteers receive high quality counseling and medical care, either directly or via referral to other organizations

• Protocol G: A large, multicenter effort to find new, naturally occurring antibodies capable of neutralizing a wide variety of HIV strains continues at research centers in Uganda, Zambia, Kenya, Rwanda, South Africa, Thailand, Cote D’Ivoire, Nigeria, Australia, United Kingdom and the U.S. Collaborating researchers screen HIV-infected volunteers who have remained healthy for at least three years after becoming infected to identify those who might produce broadly neutralizing antibodies (bnAbs) to HIV. Blood samples taken from these volunteers are screened for bnAbs, and antibody-producing cells are isolated from those that appear to have them. This global hunt feeds into IAVI’s Neutralizing Antibody Consortium (NAC). Thanks largely to the efforts of this consortium, the four bnAbs identified so far have been studied in atomic detail to explain how each neutralizes HIV. Insights from such studies are already being applied to design what we hope will be a new generation AIDS vaccine candidates. We expect that the discovery of more bnAbs and the potential elucidation of novel mechanisms of HIV neutralization will contribute significantly to the global quest to develop an AIDS vaccine. A World Bank assessment of IAVI noted that Protocol G received the highest praise from peer research and development organizations. "This work," the report noted, "is seen as using IAVI's infrastructure to offer unique value to the field."

• Protocol H: A clinical follow-up study of volunteers in previous IAVI-sponsored vaccine trials who subsequently become HIV positive continues in Rwanda, Kenya and Zambia. The study compares clinical, laboratory, immunologic and viral markers of disease progression in those who received the vaccine candidate and those that got the placebo, and is similar in many regards to Protocol C.

• LTFU: A long-term follow-up study of volunteers who participated in previous IAVI-sponsored HIV vaccine trials continues at research centers in India, Uganda, Kenya, Rwanda, Zambia and South Africa. HIV tests and health assessment questionnaires are given to all volunteers every six months. Blood collected from volunteers who participated in select studies is also assessed for the persistence of the immune response generated during the trial

Aside from providing information critical to future vaccine trials as well as insights into the appropriate design of candidate AIDS vaccines, IAVI-supported research benefits the communities in which it is conducted in a variety of ways. It helps build technical capacity in collaborating institutions, and in some cases even improves the quality of certain health care services in participating communities. More than 100,000 people in sub-Saharan Africa have, for instance, received voluntary counseling and HIV testing services due to their participation in studies supported by IAVI.