Studies of HIV-exposed, but uninfected, individuals (including infants of HIV-seropositive mothers) have demonstrated that exposure to HIV can sometimes lead to the development of HIV-specific cell-mediated immune responses. Whether these responses are merely markers of exposure or whether they signify actual protective immunity is still unknown. The Principal Investigator proposes to pursue these questions in the context of studies of maternal-infant HIV transmission being conducted at two sites in South African: Baragwanath Hospital, Soweto, Johannesburg and King Edward Hospital, Durban. These sites are currently participating in a placebo-controlled, clinical trial coordinated by UNAIDS of short-course anti-retroviral treatment (combinations of zidovudine and lamivudine) to prevent mother-to-child HIV transmission (the PETRA Study) and plan to continue with clinical follow- up of the offspring of HIV-seropositive women following the end of enrollment into this trial. For proposed project, the researchers will collect cord blood from 200 infants and will perform tests on-sit of cellular immune responses (in vitro T-cell reactivity to HIV and other antigens). The will test the hypothesis that infants who display in vitro T-helper cell activity to HIV (T-1HIV) are less likely to be HIV-infected than those who do not display this response. Also, because many of the women enrolled will probably choose to breast feed their infants, they will test prospectively whether infants with no early evidence of HIV infection and subsequently breast- fed who displayed T-1HIV are less likely to become HIV-infected through breast-feeding transmission. The researchers will also examine associations between T-1HIV and anti-retroviral treatment and maternal viral load, persistence of cellular immune responses to six months of age, and genetic factors associated with T-1HIV and HIV infection. The proposed study involved, importantly and for the first time, a prospective test of a possible protective effect of the early cellular immune responses to HIV and subsequent challenge with HIV, in this case from breast feeding.
