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Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy.
J Infect Dis. 2007 Jun 01; 195(11):1694-704.JI

Abstract

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.

Authors+Show Affiliations

British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17471440

Citation

Brumme, Zabrina L., et al. "Effects of Human Leukocyte Antigen Class I Genetic Parameters On Clinical Outcomes and Survival After Initiation of Highly Active Antiretroviral Therapy." The Journal of Infectious Diseases, vol. 195, no. 11, 2007, pp. 1694-704.
Brumme ZL, Brumme CJ, Chui C, et al. Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy. J Infect Dis. 2007;195(11):1694-704.
Brumme, Z. L., Brumme, C. J., Chui, C., Mo, T., Wynhoven, B., Woods, C. K., Henrick, B. M., Hogg, R. S., Montaner, J. S., & Harrigan, P. R. (2007). Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy. The Journal of Infectious Diseases, 195(11), 1694-704.
Brumme ZL, et al. Effects of Human Leukocyte Antigen Class I Genetic Parameters On Clinical Outcomes and Survival After Initiation of Highly Active Antiretroviral Therapy. J Infect Dis. 2007 Jun 1;195(11):1694-704. PubMed PMID: 17471440.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy. AU - Brumme,Zabrina L, AU - Brumme,Chanson J, AU - Chui,Celia, AU - Mo,Theresa, AU - Wynhoven,Brian, AU - Woods,Conan K, AU - Henrick,Bethany M, AU - Hogg,Robert S, AU - Montaner,Julio S G, AU - Harrigan,P Richard, Y1 - 2007/04/24/ PY - 2006/10/03/received PY - 2006/12/18/accepted PY - 2007/5/2/pubmed PY - 2007/6/30/medline PY - 2007/5/2/entrez SP - 1694 EP - 704 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 195 IS - 11 N2 - 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. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/17471440/Effects_of_human_leukocyte_antigen_class_I_genetic_parameters_on_clinical_outcomes_and_survival_after_initiation_of_highly_active_antiretroviral_therapy_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/516789 DB - PRIME DP - Unbound Medicine ER -