title: 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.affiliation: 1 Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachusetts and Ragon Institute of Massachusetts General Hospital , MIT and Harvard, Cambridge, Massachusetts.
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.affiliation: 2 Harvard School of Public Health , Boston, Massachusetts.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.affiliation: 3 Department of Military and Community Medicine, Phramongkutklao College of Medicine , Bangkok, Thailand .
authors.forename: Ram
authors.initials: R
authors.lastname: Rangsin
authors.affiliation: 4 Research Division, Armed Forces Research Institute of Medical Sciences (AFRIMS)-Royal Thai Army , Bangkok, Thailand .
authors.forename: Thippawan
authors.initials: T
authors.lastname: Chuenchitra
authors.affiliation: 4 Research Division, Armed Forces Research Institute of Medical Sciences (AFRIMS)-Royal Thai Army , Bangkok, Thailand .
authors.forename: Narongrid
authors.initials: N
authors.lastname: Sirisopana
authors.affiliation: 5 International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 5 International Vaccine Institute, Seoul, Republic of Korea.|6 Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: 7 Department of Transfusion Medicine, Faculty of Medicine, Siriraj Hospital , Bangkok, Thailand .
authors.forename: Sasijit
authors.initials: S
authors.lastname: Vejbaesya
authors.affiliation: 8 Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand and Military Malaria Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Paris
authors.affiliation: 9 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Kenrad E
authors.initials: KE
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008889:Military Personnel; D065840:Protective Factors; D016019:Survival Analysis; D013785:Thailand
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens