17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

HIV IN GENITAL FLUIDS DURING HETEROSEXUAL TRANSMISSION

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MOAA0302

D. Boeras ¹, P. Hawkins¹, R. Haaland¹, C. Derdeyn¹, J. Mulenga², S. Allen¹, E. Hunter^1
1Emory University, Atlanta, United States, ²Zambia Blood Transfusion Services and ZEHRP, Lusaka, Zambia

BACKGROUND: Previous studies in the blood of epidemiologically linked donor and recipient pairs demonstrated that despite a heterogeneous variant population in the donor, recipient sequences detected soon after seroconversion formed a distinct, relatively homogeneous subcluster within the donor. This finding suggests that an acute genetic bottleneck occurs during the transmission process. We hypothesized that an initial genetic restriction is occuring in the genital compartment of the donor.

METHODS: A unique cohort of cohabitating HIV-1 discordant couples in Lusaka, Zambia was followed prospectively. Despite intervention methods, a small percentage of the uninfected partners seroconverted and blood and genital fluid samples were obtained to investigate the variant virus transmitted. To determine the level of viral heterogeneity in donor genital fluids, viral variants present in the donor vaginal and seminal fluids at the time of transmission were amplified and sequenced using single genome amplification.

RESULTS: Successful extraction and amplification of viral nucleic acids from donor vaginal swabs and seminal fluid allowed for sequence comparison of variants found in donor blood and genital fluids to those in the recipient‘s blood. Phylogenetic analysis of the donor derived envelope sequences (V1-V4) from five females and two males revealed an overall subclustering of genetic variants within the donor genital compartment. Yet, from these seven transmission pairs it does not appear that the genetic variant in the recipient is derived from these genitally enriched populations.

CONCLUSIONS: These preliminary data argue that the severe genetic bottleneck observed in newly infected partners does not originate from the genitally enriched variant populations. Because heterosexual transmission of HIV-1 is the predominant mode of transmission worldwide and non-subtype B viruses prevail in many developing countries, this study can directly address critical questions about where genetic bottlenecks occur during transmission - novel information that will be relevant to the development of vaccines and microbicides.

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2008-08-13
MOAA0302

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