By applying advances in molecular biology and molecular genetics to population based studies of HIV-1 infection, VEB investigators help elucidate the distribution, determinants, and natural history of this cancer-associated virus. HIV-1 RNA levels and DNA detection: We measured longitudinal HIV-1 RNA levels in a cohort of HIV-1-infected homosexual men and found that these levels increased with time for most subjects; the rate of increase predicted the risk of AIDS. These data were used by a PHS panel convened to make recommendations for optimal treatment of HIV-1-infected patients. Higher HIV-1 RNA levels were also found to predict maternal-infant HIV-1 transmission. Detection of HIV-1 DNA in umbilical cord blood did not readily distinguish in-utero infection of infants from that occurring during the intrapartum or early post-partum periods. Chemokine receptors and HLA: We identified an HIV-1-infected hemophiliac who was homozygous for the CC-chemokine receptor 5 (CCR5) 32 base pair deletion, thereby demonstrating that CCR5 is not required for HIV-1 infection. We are conducting an intensive virological investigation to determine the chemokine receptor pattern of the infecting virus. Heterozygosity for a polymorphism of CCR2b, a minor HIV-1 receptor, was found to impact the AIDS incubation period. Potentially beneficial and disadvantageous human leukocyte antigens were demonstrated through an algorithm that was developed in one cohort and tested in a separate cohort of HIV-1-infected homosexual men who were at high risk of developing AIDS.
