Primary AppointmentMicrobiology, Immunology, and Cancer Biology
Jordan Hall, Room 7088
Charlottesville, VA 22903
HIV diversity, evolution, fitness, drug resistance and disease progression
Human immunodeficiency viruses (HIV) crossed the species barrier from non-human primates multiple times in Central Africa leading to the establishment of two distinct HIV types (HIV-1 and HIV- 2) which are further sub-classified into groups (HIV-1: groups M, N, O and P and HIV-2 groups A and B). Group M dominates the epidemic with 9 subtypes and about 55 circulating recombinant forms (CRF). The low prevalence and poor establishment of groups N, O, P as well as HIV-2 may be attributable to viral factors such as poor transmissibility and fitness or host restriction factors including HLA types. The role of this divergent evolution in the development of drug resistance, fitness and disease progression among HIV and SIV strains remains largely unknown. Despite the abundance of studies on the pattern of drug resistance and disease progression in HIV-1 subtype B patients, there is a paucity of similar data on HIV genotypes circulating in sub-Saharan Africa where the epidemic is hitting the hardest. Such studies are of particular importance at a time when the roll out of Highly Active Antiretroviral Therapy (HAART) in sub-Saharan Africa is gradually making a difference. Through collaboration with Dr. Pascal Bessong at the University of Venda (Univen), Thohoyandou, in the Limpopo Province of Northern South Africa, we have established contacts with HIV clinics throughout the Province that have been administering HAART since 2004. Studies include the establishment of electronic databases that would facilitate treatment follow-up and outcome studies, utilizing novel genotypic and phenotypic assays to determine reasons for HAART failure and the pattern of drug resistance development especially in subtype C. These studies are performed on site at the University of Venda and also in our UVa laboratories and involve joint collaboration of Faculty, Staff and students from both Universities. At our UVa laboratory, we continue to study by in vitro mutagenesis experiments how the divergent evolution of HIV group O has affected resistance to novel antiretrovirals. We are also expanding on earlier studies of drug resistance development to include aspects of fitness and disease progression in CRF02_AG and CRF06cpx strains, the most prevalent recombinant HIVs in West and Central Africa. Using recent molecular Bayesian analyses methods coupled with our phenotypic analyses, old and recent sequences from the HIV database will be used to reconstruct the dissemination dynamics of CRF02_AG and CRF06cpx strains in West and Central Africa during the last 2 decades.