66 The Biology of HIV-1 Transmission and Re-infection B Chohan1,2, L Lavreys2, S Rainwater1, M Sagar1,2, K Mandaliya3, K Mandaliya, and Julie Overbaugh*1 1Fred Hutchinson Cancer Res Ctr, Seattle, WA, USA; 2Univ of Washington, Seattle, USA; and 3Coast Provincial Gen Hosp, Mombasi, Kenya

The viruses present during chronic HIV-1 infection are genetically and phenotypically diverse, and thus are likely to differ in their fitness for transmission to a new host. The variants that are most successful at spreading from host to host are important targets for vaccine design, microbicides and other interventions.  To characterize these viruses, we have been examining HIV-1 variants present soon after infection in women who are part of a prospective cohort study in Kenya that was established in 1993.  Our studies showed that although the types of virus that are transmitted may in some cases be genetically heterogeneous, they nonetheless share some common signature sequence characteristics that may distinguish them from variants present at later stages.  

In this cohort of high-risk women, who continue to be exposed to HIV-1, we have found that intersubtype superinfection is surprisingly common. Three cases of superinfection were identified in the 20 women examined to-date. These 20 women were chosen for study because they were initially infected with non-A subtypes (C or D), whereas most of the circulating strains in Kenya are subtype A.  Subtype A superinfection was detected in 3 cases that included approximately 70 person-years of follow-up, a period in which ~ 6 new infections would be predicted to occur in a similar population of HIV-1 negative women.  This result suggests that the barrier to re-infection by a second subtype may be relatively low in women who acquire HIV-1 through heterosexual contact.  It will be important to define the immunological responses in these women and to determine if intrasubtype reinfection occurs as commonly as intersubtype reinfections.