Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

Abstract

Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age. Likelihood ratio tests based on a proportional hazards model adjusting for maternal CD4 T cell count and HIV-1 viral load at 32 weeks of gestation were used to test associations between infant allelic variation and incident HIV-1 infection. Among 433 infants, 76 (18%) were HIV-1 infected during 12 months of follow-up. HLA B*18 was associated with a significantly lower risk of early HIV-1 transmission [relative risk (RR) = 0.26; 95% confidence interval (CI) 0.04-0.82], and none of the 24 breastfeeding infants expressing HLA B*18 who were uninfected at month 1 acquired HIV-1 late via breast milk. We observed a trend toward increased early HIV-1 acquisition for infants presenting HLA A*29 (RR = 2.0; 95% CI 1.0-3.8) and increased late HIV-1 acquisition via breast milk for both Cw*07 and Cw*08 (RR = 4.0; 95% CI 1.0-17.8 and RR = 7.2; 95% CI 1.2-37.3, respectively). HLA B*18 may protect breast-feeding infants against both early and late HIV-1 acquisition, a finding that could have implications for the design and monitoring of HIV-1 vaccines targeting cellular immune responses against HIV-1.

Immunogenetics and infectious diseases: special reference to the mayor histocompatibility complex

“…The HLA-B*18 allele was associated with a significantly lower risk of early HIV-1 transmission. An increase in the early acquisition of HIV-1 was also observed in children who had the HLA-A*29 allele [88]. Transmission is increased if the fetus or the newborn has the HLA-DRB1*03011 allele, while the HLA-DR13 antigen and the HLA-DRB1*1501 allele would appear to protect against infection [89].…”

Human Leucocyte Antigen Class I Diversity among Human Immunodeficiency Virus Exposed Negative and Positive Children in Cameroon

“…For example, HLA B*18 has been associated with a significantly lower risk of early HIV-1 transmission from mother to child [36]. HLA-B*45, -B*49, and -B*50 have been found at a moderately increased frequency among individuals responding to HIV-1 infection with a marked circulating and infiltrative CD8 T-cell lymphocytosis, and presenting a slow rate of CD4 T-cell decline, very low frequency of opportunistic infections, and low viral strain heterogeneity [37].…”

Mother‐to‐infant transmission of multiple blood‐borne viral infections from multi‐infected mothers

“…CTLs responses play an important role in control of HIV-1 [McMichael and Rowland-Jones, 2001] and HCV [Ibe et al, 1998;Gruner et al, 2000] replication and transmission [Goulder et al, 2001]. In mother-to-infant transmission specific class I and II MHC alleles among infants have been associated with protective effect from perinatal HIV-1 [Winchester et al, 1995;MacDonald et al, 2001;Farquhar et al, 2004] and HCV [Bosi et al, 2002] transmission. Therefore in the single patient, a given class-1or -2 MHC might protect against a virus and favor infection by a different one.…”