K. S. MACDONALD, J. CASTILLO, J. E. EMBREE, S. NJENGA, J.D. NAGELKERKE NICOLAS, I. NGATIA, Z. MOHAMMED. Mount Sinai Hospital, 1484-600, University Avenue, Toronto, Ontario, M5G 1X5; University of Manitoba, Canada University Of Nairobi, Nairobi, Kenya

Objectives: We sought to determine whether specific class I Human Leucocyte Antigens (HLA) or the degree of maternal-child sharing of class I HLA, were associated with differential risk of HIV-1 transmission.

Methods: HIV-1 infected mothers and their infants within the University of Nairobi Perinatal Transmission and Pediatric AIDS Cohort, underwent serological class I HLA typing. Class I HLA matching between mother and infant was scored from 3/6 to 6/6. Class I determinants at a frequency of greater than 5% were examined for an association with differential risk of HIV-1 transmission. Serologically defined determinants associated with differential risk were molecularly confirmed and subtyped. HIV-1 status was determined by a combination of HIV-1 serology and PCR.

Results: One hundred and sixty infants born to 125 mothers were enrolled. Nineteen were classified as perinatally infected and 141 were uninfected at birth. Of these, 20 subsequently acquired HIV-1 during follow-up from breast feeding. HLA-A2 was strongly associated with a decreased risk of perinatal HIV-1 transmission. (Odds Ratio: 0.11; 95% CI, 0.02-0.55, P = .006 multivariate analysis). Molecular subtyping of HLA-A2 in this population revealed a number of allelic subtypes including A*0201, A*0202, A*0205 and A*0214. In addition, maternal-child class I HLA concordance was independently associated with an increased risk of perinatal but not breastmilk transmission of HIV-1. (OR = 2.63; 95%CI, 1.36-5.07; P = .003)

Conclusions: The HLA determinant HLA-A2 comprising a number of allelic subtypes, and class I HLA discordance were independently protective in perinatal HIV transmission but not breastmilk transmission. This points to independent but additive mechanisms of protection potentially mediated by both HLA restricted cellular effectors and anti-HLA alloimmune responses.

Presented at:

12^th WORLD AIDS CONFERENCE, Geneva, Switzerland, June 28-July 3, 1998.

©Copyright 1999 Last Modified