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Session 24 Oral Abstract Session Antiretroviral Chemotherapy: Pathogenesis of Primary HIV Infection Session Time: Wednesday, 10 am - 12:30 pm Room 6A-B

12:15   100. Correlates of Viral Diversity in Primary HIV-1 Infection in Women M. Sagar*1,2, L. Lavreys3, J. Baeten2, B. Richardson2, K. Mandaliya3, J. Kreiss2, and J. Overbaugh1 1Fred Hutchinson Cancer Res. Ctr., Seattle; 2Univ. of Washington, Seattle; and 3Coast Provincial Gen. Hosp., Mombasa, Kenya Background: The majority of women are infected by multiple viral variants while the remainder harbor a homogeneous virus population early in their infection. It is unknown what factors predict whether multiple HIV-1 variants will be transmitted and what impact the genetic complexity of the infecting virus has on disease progression. Methods: Viral diversity was analyzed in a cohort of women by amplifying envelope sequences from a minimum of 20 proviral genomes, as quantified by real-time PCR, and analyzing the genotypic heterogeneity using the heteroduplex mobility assay. Factors related to infection and disease progression were compared using chi2 and Mann Whitney U-tests and were modeled over time using linear mixed effects models. Results: To date, we have shown that the initial HIV-1 proviral population from 61 of 102 (60%) women is heterogeneous at or near seroconversion. Demographic and behavioral factors were not associated with the complexity of the initial infecting virus population. We found no association between the presence of sexually transmitted diseases at or near the time of infection and the genetic diversity of the initial virus population. At or near the time of infection. Women with initial viral diversity were more likely to have used oral contraceptive pills (OR 4.3, 95% CI 1.5-12.8, p<0.006), Depo medroxyprogesterone (OR 4.6, 95% CI 1.5-13.4, p<0.004) or any form of hormonal contraception (OR 4.2, 95% CI 1.8-10.1, p< 0.001) as compared to women with an initial homogeneous virus population. The median of the first viral load measured between 4 months and 12 months post-infection was higher in women with initial viral heterogeneity (median 100,000, range 3020-1,659,586) as compared to women with homogeneity (median 45,709, range 478-8,511,380) (p=0.02) and this difference persisted in measurements over 5 years post-infection. The median of the first CD4 count measured between 4 months and 5 years post-infection was significantly lower in women with viral heterogeneity (median 394, range 49-978) as compared to women with initial homogeneity (median 460, range 88-949) (p = 0.03) and this difference persisted over 5 years of follow-up. Conclusion: Hormonal contraception use near the time of infection was associated with acquisition of a genetically complex virus population. An initial heterogeneous virus population is associated with faster disease progression as measured by HIV-1 plasma viral load and CD4 count.

©2002 9th Conference on Retroviruses and Opportunistic Infections