The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.Molecular surveillance has revealed significant heterogeneity in the prevalence and geographic distribution of various subtypes worldwide (5,35,36). For example, subtype B viruses account for an estimated 12.3% of cases globally, but infections with this subtype are primarily seen in the Americas, Western Europe, and Australia (35). Conversely, subtype C viruses were estimated to have caused Ͼ47% of the worldwide infections, with the highest incidence in southern African countries, Ethiopia, and India (35). As with the nonrecombinant subtypes, circulating recombinant forms (CRFs) also show founder effects and uneven geographic distributions. For example, CRF01_AE appears to be the cause of a high proportion of infections in Southeast Asia and seems to be largely confined to that area of the world with relatively little spread into other populations (35). In contrast, CRF02_AG contributes to a major number of new infections in West Africa and appears to be associated with rapidly spreading epidemics in West African countries (3,6,7,28,31,35,37). The underlying causes of the varied geographic distributions are most likely founder effects with other contributing factors, such as human population movements, unregulated commercial sex work, and intravenous drug use.Over the course of an 18-year prospective study monitoring a cohort of female sex workers (FSWs) in Dakar, Senegal, we found that the most prevalent circulating strain in the cohort is CRF02_AG, as seen in other parts of West Africa (2,6,7,28,31,35,37). However, recent work conducted in our lab revealed that a unique group of viruses within the human immunodeficiency virus type 1 (...