Background:  When children acquire HIV infection from their mother (with whom they share at least 50% of their HLA alleles), they acquire virus with a history of encounter with maternal HLA-mediated immune responses. We sought to investigate whether HLA selection pressure would adversely influence clinical outcomes of HIV-infected children. The underlying idea is that virus transmitted to the child has evolved to evade maternal HLA-mediated responses. To the extent that the child relies on these same HLA-mediated responses to contain viral replication, the child’s immune response may be set up to fail.

Methods:  We examined whether time to diagnosis with clinical AIDS or death among a cohort of 59 HIV-infected children in New York City followed from birth for as long as 12 years was associated with maternally or paternally inherited child HLA class I alleles, and with HLA gene similarity between mother and child. High resolution HLA class I typing was undertaken for the children and their mothers.

Results:  HLA disease-progression associations were modified by whether the allele was inherited from the mother or from the father. If HLA alleles usually associated with “slow disease” (e.g., A*11, B*27, B*57) or “rapid disease” (e.g., B*35, B*53, Cw*4) were inherited from the father expected HLA disease-progression associations were observed. However, if these same alleles were inherited from the mother, no associations between these alleles and disease progression were observed. We also investigated the extent of HLA class I similarity between children and mothers. Children with 2 or more loci shared with the mother were more likely to progress to AIDS or death than other children (relative hazard 3.48; 95% confidence interval: 1.24 - 9.80). These findings remained robust after adjusting for markers of the severity of maternal disease, taking into account antiretroviral drug therapy, and restricting to African American children.

Conclusions:  Genetic similarity between mother and child may compromise the child’s capacity to control HIV replication when the virus is acquired from the mother. HLA-mediated selective pressures on the virus in a transmitting mother-infant pair may undermine future HLA-mediated viral control in the child.

Keywords: HLA; disease progression