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

• Published in: AIDS (London) Vol. 16; no. 17; pp. 2275 - 2284
• Main Authors: JIANMING TANG, WILSON, Craig M, MELETH, Shreelatha, MYRACLE, Angela, LOBASHEVSKY, Elena, MULLIGAN, Mark J, DOUGLAS, Steven D, KORBER, Bette, VERMUND, Sten H, KASLOW, Richard A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 22.11.2002
• Subjects: Adolescent; AIDS/HIV; Algorithms; Alleles; Biological and medical sciences; CD4 Lymphocyte Count; Female; Follow-Up Studies; Genes, MHC Class II; Genetic Markers; Genetic Predisposition to Disease; Haplotypes; Histocompatibility Testing; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV-1; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Prognosis; Receptors, CCR2; Receptors, Chemokine - genetics; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Viremia - genetics; Viremia - immunology; Viremia - virology; HIV-1; Prognosis; HIV-1 virus; Pathogenesis; Viremia; Chemokine receptor; Genetic determinism; Prevention; genetics; CCR5; Class I histocompatibility antigen; Human; Immunopathology; adolescents; Retroviridae; AIDS; Lentivirus; Algorithm; Immune deficiency; Infection; Virus; Viral disease; Adolescent; Human immunodeficiency virus; Predictive factor; HLA
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200211220-00007

To evaluate the correlation between host genetic profiles and virological and immunological outcomes among HIV-1-seropositive participants from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. 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. 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 x 10(6) cells/l) 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 x 10(6) cells/l) or the remainder (n = 134) of the cohort (overall P < 0.0001). 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.