PMID- 17471440
OWN - NLM
STAT- MEDLINE
DCOM- 20070629
LR  - 20070501
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 195
IP  - 11
DP  - 2007 Jun 1
TI  - Effects of human leukocyte antigen class I genetic parameters on clinical 
      outcomes and survival after initiation of highly active antiretroviral therapy.
PG  - 1694-704
AB  - 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). CONCLUSION: 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.
FAU - Brumme, Zabrina L
AU  - Brumme ZL
AD  - British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
FAU - Brumme, Chanson J
AU  - Brumme CJ
FAU - Chui, Celia
AU  - Chui C
FAU - Mo, Theresa
AU  - Mo T
FAU - Wynhoven, Brian
AU  - Wynhoven B
FAU - Woods, Conan K
AU  - Woods CK
FAU - Henrick, Bethany M
AU  - Henrick BM
FAU - Hogg, Robert S
AU  - Hogg RS
FAU - Montaner, Julio S G
AU  - Montaner JS
FAU - Harrigan, P Richard
AU  - Harrigan PR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070424
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (HLA Antigens)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Adult
MH  - *Antiretroviral Therapy, Highly Active
MH  - Cohort Studies
MH  - Female
MH  - HIV Infections/*drug therapy/genetics/immunology/*mortality/virology
MH  - HIV-1/*drug effects/physiology
MH  - HLA Antigens/*genetics
MH  - Histocompatibility Testing
MH  - Humans
MH  - Male
MH  - Multivariate Analysis
MH  - Proportional Hazards Models
MH  - RNA, Viral/blood
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - Viral Load
EDAT- 2007/05/02 09:00
MHDA- 2007/06/30 09:00
CRDT- 2007/05/02 09:00
PHST- 2006/10/03 00:00 [received]
PHST- 2006/12/18 00:00 [accepted]
PHST- 2007/05/02 09:00 [pubmed]
PHST- 2007/06/30 09:00 [medline]
PHST- 2007/05/02 09:00 [entrez]
AID - JID37608 [pii]
AID - 10.1086/516789 [doi]
PST - ppublish
SO  - J Infect Dis. 2007 Jun 1;195(11):1694-704. doi: 10.1086/516789. Epub 2007 Apr 24.