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.


METHODS
A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 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 (CXCR4) co-receptors.


RESULTS
HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 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/delta32 children transmission occurred only at viral loads greater than 4.0 log10 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/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants.


CONCLUSIONS
Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.
Ometto
L
L
Department of Oncology and Surgical Sciences, AISA Reference Center, University of Padua, Italy.
Zanchetta
M
M
Mainardi
M
M
De Salvo
G L
GL
Garcia-Rodriguez
M C
MC
Gray
L
L
Newell
M L
ML
Chieco-Bianchi
L
L
De Rossi
A
A
D017332:Cetirizine; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006679:HIV Seropositivity / Q000635:transmission*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D019713:Receptors, CCR5 / Q000235:genetics*; D019718:Receptors, CXCR4; D019562:Viral Load
D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017332:Cetirizine