Associations of chemokine receptor polymorphisms With HIV-1 mother-to-child transmission in sub-Saharan Africa: possible modulation of genetic effects by antiretrovirals.
BACKGROUND
HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa.


METHODS
Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT.


RESULTS
In antiretroviral-naive mother-infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1-infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT.


CONCLUSIONS
CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093-0672, USA.
Kumud K
KK
Singh
Michael D
MD
Hughes
Jie
J
Chen
Kelesitse
K
Phiri
Christine
C
Rousseau
Louise
L
Kuhn
Anna
A
Coutsoudis
J Brooks
JB
Jackson
Laura A
LA
Guay
Philippa
P
Musoke
Francis
F
Mmiro
Richard D
RD
Semba
Stephen A
SA
Spector
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000635:transmission*; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000073883:CX3C Chemokine Receptor 1; D005260:Female; D015497:HIV-1; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011110:Polymorphism, Genetic; D011247:Pregnancy; D054390:Receptors, CCR2 / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics*
D019380:Anti-HIV Agents; C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine