Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy.
BACKGROUND
Human leukocyte antigen (HLA) class I variation influences the progression of untreated human immunodeficiency virus (HIV) disease; however, it is not known whether HLA class I variation may influence clinical outcomes after initiation of highly active antiretroviral therapy (HAART).


METHODS
Associations between HLA class I genotypes and pretherapy clinical parameters were investigated in a cohort of 765 antiretroviral-naive adults initiating HAART. Cox proportional hazards regression was used to investigate the effects of HLA class I genotypes on time to suppression of the viral load to <500 HIV RNA copies/mL, time to an increase in the CD4 cell count to >100 cells/mm(3) above the baseline count, and time to nonaccidental death over a >5-year period after initiation of HAART.


RESULTS
Homozygosity at any HLA class I locus and possession of common HLA alleles were associated with a higher pretherapy viral load (P<.05). In multivariate analyses controlling for sociodemographic and clinical parameters at baseline, HLA class I homozygosity was significantly associated with a poorer CD4 cell response (P=.008), whereas possession of uncommon HLA alleles was associated with slower virologic suppression after initiation of HAART (P=.02). We observed no significant association between HLA parameters and time to nonaccidental death after initiation of HAART (P>.05, univariate analysis).


CONCLUSIONS
HLA class I zygosity-dependent and frequency-dependent effects may influence short-term HAART outcomes, and, thus, they deserve further investigation. No effects of these HLA parameters on survival after initiation of HAART were observed.
Brumme
Zabrina L
ZL
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
Brumme
Chanson J
CJ
Chui
Celia
C
Mo
Theresa
T
Wynhoven
Brian
B
Woods
Conan K
CK
Henrick
Bethany M
BM
Hogg
Robert S
RS
Montaner
Julio S G
JS
Harrigan
P Richard
PR
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000401:mortality* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
D006680:HLA Antigens; D012367:RNA, Viral