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Session 51 Poster Session Impact of Host Genetics on Viral Transmission and Disease Progression Session Time: 4:30-6:30 pm Room 4E-F

325-W. Host Genetic Profiles Strongly Correlate with Virologic and Immunologic Outcomes in HIV-1 Seroprevalent and Primarily African American Adolescents J. Tang*, C. M. Wilson, S. Meleth, M. Shaen, A. Myracle, E. Lobashevsky, M. Mulligan, and R. A. Kaslow for the REACH Cohort Study Group Univ. of Alabama, Birmingham Background: HIV-1 pathogenesis can be regulated by host genetic variations at several loci involved in natural and acquired immunity. We evaluated the correlation between host genetic profiles (defined by HLA and HIV-1 coreceptor variants) and the virologic and immunologic outcomes among HIV-1-infected adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: 227 HIV-1-seropositive REACH adolescents (ages 13-18, 75% females, and 71% African Americans) with quarterly follow-up visits (1996-2000) were categorized into 3 groups based on average plasma HIV-1 RNA concentration (viral load [VL] in copies/mL) and CD4+ T-cell counts (cells/muL) during a 6-12 months interval when antiretroviral therapy (ART) was not taken. HLA class I and HIV-1 co-receptor (CCR) alleles and haplotypes were resolved using PCR-SSP, reference-strand conformation analysis, and DNA sequencing. Each HLA and CCR variant with a previously reported risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. Individuals with identical net scores were grouped and analyzed in relation to VL and CD4+ cell counts. Multivariable models were applied to assess the relative effects of genetic scores along with other host variables including race, gender, and prior exposure to ART. Results: Adolescents (n=40) with a clearly favorable combination of VL (<1000) and CD4 counts (>450) consistently had more positive (+1 to +2) than negative (-1 to -4) scores compared with those (n=80) with an unfavorable combination (VL >16,000 and CD4 <450) or the remainder (n=107) of the cohort (p<0.0001). Close association of genetic profile with mean log10 VL remained persistent (p<0.0001) after adjustment for differences in gender (p=0.048), race (p=0.721), and history of ART (p=0.001). Conclusions: Strong and consistent association between host genetic profile and virologic/immunologic control of HIV-1 infection in primarily African American youth suggests that readily available HLA class I and CCR genotyping data can offer another tool for predicting clinical outcomes. The prognostic value of our genetic scoring algorithm in both clinical and investigative settings will undoubtedly improve as effects of additional host genetic factors are revealed and confirmed.

©2002 9th Conference on Retroviruses and Opportunistic Infections