This application, entitled Molecular Epidemiology and Viral Evolution in HIV-2 and HIV-1/HIV-2 Dually Infected Individuals in Senegal, for a K08 Mentored Clinical Scientist Development Award, will help enable Dr. Geoffrey S. Gottlieb, under the sponsorship of Dr. James I. Mullins and collaborators at the University of Washington School of Medicine and the University of Dakar, Senegal, to acquire the skills necessary to continue to pursue the immediate goals of this research plan as well as to continue his path toward an innovative and productive independent academic research career as a physician-scientist. A global understanding of the diversity and evolution of Human Immunodeficiency Viruses (HIVs) will be important to developing prophylactic vaccines and understanding the pathogenesis of AIDS. Although structurally and genetically similar, HIV-1 and HIV-2, behave quite differently, both at the level of the individual patient and as agents of the global epidemic. The reasons for this are not clear. Evidence suggests that patients dually infected with both HIV-1 and HIV-2 have greater control of their viral burden. Our longitudinally followed cohort of Senegalese individuals whom are infected with HIV-1, HIV-2 or both viruses provides a unique opportunity to study the molecular epidemiology and evolutionary dynamics of AIDS in West Africa and to correlate them with virologic, immune and clinical outcomes. This application will examine the following hypotheses: 1) If intra-patient, HIV-2 viral diversity and divergence will be attenuated compared to that seen in HIV-1 and if the rate of HIV evolution, as measured by viral divergence and diversity, will be slower in dually infected individuals. Whether emergence of CXCR4 HIV-1 variants will be delayed in dually infected individuals and whether these events correlate with immune status, viral load and clinical outcomes; 2) That cross-reactive immune responses and viral interference between HIV-1 and HIV-2 selects for infection with unique HIV-1 subtypes in dually infected individuals; and 3) If recombinant HIV-1/HIV-2 viruses can emerge in dually infected individuals and if they do, whether they alter the natural history of HIV infection in these people.
