Maternal versus paternal inheritance of HLA class I alleles among HIV-infected children: consequences for clinical disease progression.
OBJECTIVE
When children acquire HIV infection from their mothers (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 investigated whether maternal HLA selection pressures on the virus would adversely influence clinical outcomes of HIV-infected children.


METHODS
We tested whether time to AIDS diagnosis or death, among a cohort of 59 HIV-infected children in New York City followed from birth for up to 12 years, was associated with maternally- or paternally-inherited child HLA class I alleles, and with HLA similarity between mother and child.


RESULTS
HIV-infected children with an HLA allele usually associated with slow disease experienced a slower progression to AIDS or death only if the allele was paternally inherited. If the allele was present in the mother, no association was observed. Children who were homozygous or who shared both alleles with their mothers at more than one HLA class I locus were more likely to progress to AIDS or death than other children (relative hazard, 3.46; 95% confidence interval, 1.24-9.71).


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.
Kuhn
Louise
L
Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
Abrams
Elaine J
EJ
Palumbo
Paul
P
Bulterys
Marc
M
Aga
Ronnie
R
Louie
Leslie
L
Hodge
Thomas
T
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000401:mortality; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005220:Fathers; D005260:Female; D005805:Genes, MHC Class I; D015658:HIV Infections / Q000235:genetics* / Q000401:mortality / Q000635:transmission; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009035:Mothers; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D019562:Viral Load