Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission

Objective: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. Patients and methods: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and Delta 32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR3) co-receptors. Results: HIV-1 transmission rates in wt/wt and wt/Delta 32 mothers (14.7 versus 15.8%), and in wt/wt and wt/Delta 32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/Delta 32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log(10) copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/Delta 32 children transmission occurred only at viral loads greater than 4.0 log(10) copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/Delta 32 mothers with an R5-type virus transmitted HIV-1 to their wt/Delta 32 infants. Conclusion: Taken together, these findings suggest that CCR5 Delta 32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolat