Maternal HLA homozygosity and mother-child HLA concordance increase the risk of vertical transmission of HIV-1.
BACKGROUND
Mother-child human leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses.


METHODS
We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load.


RESULTS
Among 277 mother-infant pairs, HIV-1 transmission occurred in 58 infants (21%), with in utero transmission in 21 (36%), peripartum transmission in 26 (45%), and transmission via breast-feeding in 11 (19%). With increased concordance, we observed a significant increase in the risk of transmission overall (adjusted hazard ratio [aHR], 1.3 [95% confidence interval {CI}, 1.0-1.7]; P = .04 in utero (adjusted odds ratio, 1.72 [95% CI, 1.0-1.7]; P = .04), and via breast-feeding (aHR, 1.6 [95% CI, 1.0-2.5]; P = .04). Women with homozygosity had higher plasma HIV-1 RNA levels at 32 weeks of gestation (5.1 vs. 4.8 log(10) copies/mL; P = .03) and an increased risk of transmission overall (aHR, 1.7 [95% CI, 1.1-2.7]; P = .03) and via breast-feeding (aHR, 5.8 [95% CI, 1.9-17.7]; P = .002).


CONCLUSIONS
The risks of overall, in utero, and breast milk HIV-1 transmission increased with HLA concordance and homozygosity. The increased risk may be due to reduced alloimmunity or less diverse protective immune responses.
Mackelprang
Romel D
RD
Department of Epidemiology, University of Washington, Seattle 98104, USA.
John-Stewart
Grace
G
Carrington
Mary
M
Richardson
Barbra
B
Rowland-Jones
Sarah
S
Gao
Xiaojiang
X
Mbori-Ngacha
Dorothy
D
Mabuka
Jennifer
J
Lohman-Payne
Barbara
B
Farquhar
Carey
C
D001942:Breast Feeding; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000821:virology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood
D004279:DNA, Viral; D006680:HLA Antigens; D012367:RNA, Viral