Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents

Jianming Tang, Craig M. Wilson, Shreelatha Meleth, Angela Myracle, Elena Lobashevsky, Mark J. Mulligan, Steven D. Douglas, Bette Korber, Sten H. Vermund, Richard A. Kaslow, L. Friedman, L. Pall, D. Maturo, A. Pasquale, D. Futterman, D. Monte, M. Alovera-DeBellis, N. Hoffman, S. Jackson, D. SchwarzB. Rudy, M. Tanney, A. Feldman, M. Belzer, D. Tucker, C. Hosmer, K. Chung, S. E. Abdalian, L. Green, C. McKendall, L. Wenthold, L. J. D'Angelo, C. Trexler, C. Townsend-Akpan, R. Hagler, J. A. Morrissy, L. Peralta, C. Ryder, S. Miller, S. Calianno, L. Henry-Reid, R. Camacho, M. Sturdevant, A. Howell, J. E. Johnson, A. Puga, D. Cruz, P. McLendon, M. Sawyer, J. Tigner, A. Simmonds, P. Flynn, K. Lett, J. Dewey, S. Discenza, L. Levin, M. Geiger, P. Stanford, F. Briggs, J. Birnbaum, M. Ramnarine, V. Guarino, C. Holland, A. B. Moscicki, D. A. Murphy, P. Crowley-Nowick, C. Partlow, S. J. Durako, J. H. Ellenberg, B. Hobbs, A. Bennett, M. Camarca, K. Clingan, J. Houser, V. Junankar, O. Leytush, L. Muenz, Y. Ma, R. Mitchell, T. Myint, P. Ohan, L. Paolinelli, M. Rakheja, M. Sarr, A. Soloviov, A. Rogers, A. Willoughby, K. Davenny, V. Smeriglio, E. Matzen, B. Vitiello

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Objective: To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-l-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Methods: HLA class I and chemokine coreceptor (CCR) alleles and haplotypes were resolved in 227 HIV-1 -seropositive adolescents (ages 13-18 years; 75% females; 71% African-Americans) and 183 HIV-seronegative individuals, with quarterly follow-up visits between 1996 and 2000. Each HLA and CCR variant with consistent risk and protective effect on HIV-1 pathogenesis was assigned a score of -1 and +1, respectively. All individual markers and genetic scores were analyzed in relation to plasma viral load (VL) and CD4 T lymphocytes during a 6-12-month interval when no antiretroviral therapy was taken. Results: HLA-B* 57 alone was a strong predictor of VL (P < 0.0001), but composite genetic profiles found in over 50% of patients consistently outperformed the individual component markers in multivariable analyses with or without adjustment for gender, race, age, and membership of clinical patient groups. Adolescents (n = 37) with a favorable combination of VL (< 1000 copies/ml) and CD4 T cell counts (> 450 × 106 cells/I) consistently had more positive (+1 to +2) than negative (-1 to -4) HLA and CCR scores compared with those (n = 56) with an unfavorable combination (VL > 16 000 copies/ml and CD4 cells < 450 × 106 cells/I) or the remainder (n = 134) of the cohort (overall P < 0.0001). Conclusion: A generalizable genetic scoring algorithm based on seven HLA class I and CCR markers is highly predictive of viremia and immunodeficiency in HIV-1-infected adolescents.

Original languageEnglish (US)
Pages (from-to)2275-2284
Number of pages10
JournalAIDS
Volume16
Issue number17
DOIs
StatePublished - Nov 22 2002

Keywords

  • Adolescents
  • CCR5
  • Genetics
  • HIV-1
  • HLA
  • Prognosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tang, J., Wilson, C. M., Meleth, S., Myracle, A., Lobashevsky, E., Mulligan, M. J., Douglas, S. D., Korber, B., Vermund, S. H., Kaslow, R. A., Friedman, L., Pall, L., Maturo, D., Pasquale, A., Futterman, D., Monte, D., Alovera-DeBellis, M., Hoffman, N., Jackson, S., ... Vitiello, B. (2002). Host genetic profiles predict virological and immunological control of HIV-1 infection in adolescents. AIDS, 16(17), 2275-2284. https://doi.org/10.1097/00002030-200211220-00007