HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort.
View/ Open
Date
2013Author
Peterson TA.
Kimani J.
Wachihi C.
Bielawny T.
Mendoza, L
Thavaneswaran, S
Narayansingh, MJ
Kariri, T
Liang, B
Ball, TB
Ngugi, Elizabeth N
Plummer, FA
Luo, M
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan–Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm3). A*01 (P = 0.020), C*06:02 (P = 0.042) and C*07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320–0.790]. Conversely, A*23:01 (P = 0.004), B*07:02 (P = 0.003) and B*42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290–3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132–0.544). B*07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A*74:01 (P = 0.04/P = 0.006), B*14 (P = 0.003/P = 0.003) and B*57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B*07:02 (P = 0.020), B*15:10 (P = 0.022) and B*53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B*35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1
URI
http://www.ncbi.nlm.nih.gov/pubmed/23330720http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/16167
Citation
Tissue Antigens.2013 Feb;81(2):93-107Publisher
HIV and Human Genetics, National Microbiology Laboratory, Winnipeg, MB, Canada. Department of Medical Microbiology, University of Nairobi Department of Community Health, University of Nairobi, Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada
Subject
Differential human immunodeficiency virus-1 seroconversion;Differential human immunodeficiency virus-1 seroconversion;
Human leukocyte antigen class I association;
Natural resistance to human immunodeficiency virus-1 infection;
Pumwani Sex Worker Cohort
Collections
- Faculty of Health Sciences (FHS) [10377]