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255 Dual HIV-1 Infection in Plasma and Genital Tract of Women
B. Weiser*1, H. Burger1, C. Chappey2, K. Anastos3, D. Mayers4, C. Kitchen5, W. A. Meyer III3, E. Paxinos2, C. Petropolis2, C.-H. Chen1, and G. Fang1
1Wadsworth Ctr., New York State Dept. of Hlth., Albany, USA; 2ViroLogic Inc., South San Francisco, CA, USA; 3Montefiore Med Ctr., NYC-WIHS, NY, USA; 4Henry Ford Hosp., Detroit, MI, USA; and 5Univ. of California, Los Angeles, USA
Background: To develop HIV-1 vaccines and therapies, we must understand mucosal transmission, viral reservoirs, and dual infection. Dual infection of the blood by distinct strains has been documented, particularly where multiple viral clades are endemic, but analyses of HIV-1 in different reservoirs have shown related viral species at each site.
Methods: To investigate HIV-1 sequence variation in blood and mucosal compartments, we studied the HIV-1 pol gene from serial, paired plasma, and genital tract samples of 8 women in the NYC Women’s Interagency HIV Study; all had received antiviral therapy. The route of infection was heterosexual transmission or injecting drug use, with 5 reporting both risks.
Results: Computational analyses of HIV-1 sequences from genital tract and plasma revealed marked differences; in 3 women, the degree of divergence between viruses in the 2 sites suggested dual infection with different viruses in different compartments. These results were derived from phylogenetic trees, pairwise analyses, and signature sequences. We are currently performing sequence analyses of the env gene from these patients as well as HTAs to confirm the presence of dual infection. Responses to antiviral therapy in the 2 compartments also differed in most patients, with greater reductions in viral load and fewer resistance mutations detected in virus from the genital tract.
Conclusions: These data demonstrate that the female genital tract can serve as a reservoir of HIV-1 that is genetically distinct from that in plasma. In particular, the findings suggest the presence of chronic dual infection, with different clade B strains infecting different sites in 3 of 5 women with risks for both parenteral and sexual exposure. The containment of different HIV-1 strains in separate compartments suggested here highlights the need to examine multiple reservoirs to understand the correlates of protection and effective therapy.
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