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


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 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).


CONCLUSIONS
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.
Tang
Jianming
J
Department of Medicine, University of Alabama at Birmingham, AL 39294-0022, USA.
Wilson
Craig M
CM
Meleth
Shreelatha
S
Myracle
Angela
A
Lobashevsky
Elena
E
Mulligan
Mark J
MJ
Douglas
Steven D
SD
Korber
Bette
B
Vermund
Sten H
SH
Kaslow
Richard A
RA
D000293:Adolescent; D000465:Algorithms; D000483:Alleles; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D005802:Genes, MHC Class II; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D011379:Prognosis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000276:immunology / Q000821:virology
C515334:CCR2 protein, human; D005819:Genetic Markers; D054390:Receptors, CCR2; D019707:Receptors, Chemokine