Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission - Effect of maternal zidovudine treatment on viral load

Objective. - To determine if there are levels of human immunodeficiency virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treatment reduces perinatal transmission. Design. - A nonrandomized prospective cohort study, Setting. - University medical center and two general hospital affiliates from May 1989 to September 1994. Patients. - Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants. Intervention. - forty-two mothers (43 pregnancies) received zidovudine therapy during pregnancy and/or during labor and delivery. Eleven infants received prophylactic zidovudine for the first 6 weeks after delivery. Main Outcome Measure. - HIV-1 infection status of the infant. Results. - Twenty of the 97 infants were perinatally infected with HIV-1. Transmitting mothers were more likely to have plasma HIV-1 RNA levels higher than 50 000 copies per milliliter at delivery than nontransmitting mothers (15 [75.0%] of 20 transmitters vs four [5.3%] of 75 nontransmitters; P<.001). None of the 63 women with less than 20 000 HIV-1 RNA copies per milliliter transmitted. Twenty-two women treated with open-label oral zidovudine during gestation showed an eightfold median decrease in plasma RNA levels (median [25th and 75th percentile], 43 043 [5699 and 63 053] copies per milliliter before zidovudine vs 4238 [603 and 5116] HIV-1 RNA copies per milliliter at delivery; P<.001), and none transmitted. Four zidovudine-treated women with high HIV-1 levels transmitted despite the presence of zidovudine-sensitive virus in vitro in both the mothers and their infants. Conclusions. - Maternal HIV-1 RNA levels were highly predictive of perinatal transmission risk and suggest that certain levels of virus late in gestation and/or during labor and delivery are associated with both a high risk and a low risk of transmission, Our results also suggest that zidovudine exerts a major protective effect by reducing maternal HIV-1 RNA levels prior to delivery and that further strategies are needed to prevent perinatal transmission in women with high or increasing virus levels and/or zidovudine-resistant virus.