HLA Class I Alleles Associated with Mortality in Thai Military Recruits with HIV-1 CRF01_AE Infection.

Abstract

In HIV-1-infected patients, variation at the HLA class I locus is associated with disease progression, but few studies have assessed the influence of HLA alleles on HIV-1 CRF01_AE infection, which is dominant in Thailand. We hypothesized that alleles predicted to confer more effective immune responses, such as HLA-B*46, would protect against disease progression. HLA typing was performed on HIV-1 incident cases surviving until 1998-1999 and HIV-1-negative matched controls from Thai army cohorts enrolled between 1991 and 1995. We assessed associations between class I alleles and disease progression subsequent to HLA typing. Ninety-nine HIV-1-incident cases were followed for a median of 3.7 years after HLA typing; during this time, 58 participants died. Two alleles were associated with mortality: HLA B*51 was protective (3-year survival B*51(pos) vs. B*51(neg): 75% vs. 52%; p = 0.034) whereas Cw*04 was deleterious (3-year survival Cw*04(pos) vs. Cw*04(neg): 39% vs. 60%; p = 0.027). HLA-B*46 was not associated with disease progression. Alleles present at different frequencies in HIV-1-incident compared with HIV-1-negative men included HLA-A*02:03, B*35, B*15, and C*08. 1. In conclusion in this Thai army cohort, HLA-B*51 was associated with lower mortality, confirming that this allele, which is protective in clade B HIV-1 infection, has a similar effect on HIV CRF01_AE infection. The deleterious effect of HLA-Cw*04 must be interpreted with caution because it may be in linkage disequilibrium with disease-susceptible HLA-B alleles. We did not find that HLA-B*46 was protective. These findings may inform vaccine development for areas of the world in which HIV-1 CRF01_AE infection is prevalent.

• Authors: Rajesh T Gandhi, Ronald J Bosch, Ram Rangsin, Thippawan Chuenchitra, Narongrid Sirisopana, Jerome H Kim, Merlin L Robb, Sasijit Vejbaesya, Robert M Paris, Kenrad E Nelson
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 32 Issue 1 Pg. 44-9 (Jan 2016) ISSN: 1931-8405 [Electronic] United States
• PMID: 26383907 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• HLA-A Antigens
• HLA-B Antigens
• HLA-C Antigens

Topics

• Adult
• Alleles
• Case-Control Studies
• Disease Progression
• Gene Expression
• Gene Frequency
• Genetic Predisposition to Disease
• HIV Infections (diagnosis, genetics, immunology, mortality)
• HIV-1 (immunology, pathogenicity)
• HLA-A Antigens (genetics, immunology)
• HLA-B Antigens (genetics, immunology)
• HLA-C Antigens (genetics, immunology)
• Histocompatibility Testing
• Humans
• Male
• Military Personnel
• Protective Factors
• Survival Analysis
• Thailand