| Abstract
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Since 1985, our laboratory has been conducting a prospective study of a cohort of registered female sex workers (FSW) in Dakar, Senegal. Initial surveys of the different HIV-1 subtypes circulating in the cohort revealed that, while a majority of the women were infected with the circulating recombinant form CRF02_AG, a distinct subcluster of viruses was also present in the FSW population. Furthermore, it appeared as if these viruses were over-represented in HIV-1/HIV-2 dually infected individuals as compared to women who were singly infected with HIV-1. The goal of this study was to characterize this distinct group of viruses. Phylogenetic analyses and pairwise distance calculations indicated that these viruses could be considered a new sub-subtype of HIV-1 group M viruses, which we have termed HIV-1 A3. We also examined the molecular epidemiology of A3 in the Dakar FSW cohort and, found evidence of A3 in 46 HIV-1-infected women. HIV-1 A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001, with an increasing incidence. We also found that HIV-1 A3 is not only confined to the FSW cohort in Senegal, but is circulating in the general population in Dakar as well as in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin and Equatorial Guinea. To better understand the reason why A3 was over-represented in dually infected subjects, we examined some biological correlates of disease and pathogenesis. We compared women infected with A3 to those with CRF02_AG and found no difference in disease progression or in viral loads at setpoint. Then, we isolated viruses from peripheral blood mononuclear cells (PBMCs) taken from infected individuals to compare the replication kinetics between A3 and CRF02_AG viruses. Isolates were used to infect PBMCs from both HIV-negative and HIV-2-infected individuals. Though there appeared to be a trend towards higher mean p24 production from cells infected with CRF02_AG, there were no statistically significant differences. In conclusion, we have characterized a new sub-subtype of HIV-1 viruses circulating in West Africa, which we have named A3. The studies described here provide a phylogenetic, epidemiological, and preliminary biological characterization of HIV-1 A3.
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