South
African mother with HIV/AIDS who has access to life-saving treatment.
It
is well known that without prophylactic antiretroviral
therapy, HIV may be transmitted from mothers to their
babies during gestation, delivery, or breast-feeding. However, besides HIV
viral load, the factors that increase the risk of perinatal transmission are not
fully understood.
In a study described in the April 15, 2008 Journal
of Infectious Diseases, an American and African research team looked at associations
between maternal and child human leukocyte antigen (HLA) patterns and likelihood
of HIV transmission.
The
HLA system, or major histocompatibility complex, is a group of genes that play
a role in immune response. Each individual carries two versions of HLA, which
may either be the same (homozygous) or different (heterozygous). Further, mothers
and their babies may either have matching (concordant) or dissimilar (discordant)
HLA patterns.
In
the present study, the researchers set out to test the hypothesis that maternal
HLA homozygosity and mother-child HLA concordance may increase the risk of vertical
HIV transmission by reducing infant immune responses. They analyzed HLA patterns
in 277 mother-infant pairs in a Kenyan perinatal cohort receiving prenatal zidovudine
(AZT; Retrovir) to reduce the
risk of HIV transmission. HLA concordance was scored as the number of shared class
I alleles. Relative risk estimates were adjusted for maternal HIV viral load.
Results
•
Among 277 mother-infant
pairs, a total of 58 infants (21%) were infected with HIV:
•
in utero:
21 (36%); •
peripartum
(during delivery): 26 (45%); •
via breast-feeding:
11 (19%).
•
As HLA concordance
increased, there was a significant rise in the risk of HIV transmission overall
(adjusted hazard ratio [AHR] 1.3), in utero (AHR 1.72), and via breast-feeding
(AHR 1.6) (all P = .04).
•
Women with
HLA homozygosity had higher plasma HIV RNA levels at 32 weeks of gestation (5.1
vs 4.8 log10 copies/mL; P = .03).
•
HLA homozygous
mothers had an increased risk of transmitting HIV overall (AHR 1.7; P = .03) and
via breast-feeding (AHR 5.8; P = .002).
Conclusion
"The
risks of overall, in utero, and breast milk HIV-1 transmission increased with
HLA concordance and homozygosity," the investigators concluded. "The
increased risk may be due to reduced alloimmunity or less diverse protective immune
responses."
University of Washington, Seattle, WA; Laboratory of
Genomic Diversity, Science Applications International Corporation-Frederick, National
Cancer Institute-Frederick, Frederick, MD; University of Nairobi, Nairobi, Kenya;
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular
Medicine, Oxford, UK.
4/18/08
Reference RD Mackelprang,
G John Stewart, M Carrington, and others. Maternal HLA Homozygosity and Mother
Child HLA Concordance Increase the Risk of Vertical Transmission of HIV 1. Journal
of Infectious Diseases 19798): 1156-1161. April 15, 2008.
Results
