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 t ransmission and to ascertain the mechanism by which zidovudine treatme nt reduces perinatal transmission. Design. A nonrandomized prospective cohort study. Setting. University medical center and two general hosp ital affiliates from May 1989 to September 1994. Patients. Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants. Interv ention. Forty-two mothers (43 pregnancies) received zidovudine therapy during pregnancy and/or during labor and delivery. Eleven infants rec eived prophylactic zidovudine for the first 6 weeks after delivery. Ma in Outcome Measure. HIV-1 infection status of the infant. Results. Twe nty of the 97 infants were perinatally infected with HIV-1. Transmitti ng mothers were more likely to have plasma HIV-1 RNA levels higher tha n 50,000 copies per milliliter at delivery than nontransmitting mother s (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 copie s 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 5 116] HIV-1 RNA copies per milliliter at delivery; P < .001), and none transmitted. Four zidovudine-treated women with high HIV-1 levels tran smitted despite the presence of zidovudine-sensitive virus in vitro in both the mothers and their infants. Conclusions. Maternal HIV-1 RNA l evels were highly predictive of perinatal transmission risk and sugges t that certain levels of virus late in gestation and/or during labor a nd delivery are associated with both a high risk and a low risk of tra nsmission. Our results also suggest that zidovudine exerts a major pro tective effect by reducing maternal HIV-1 RNA levels prior to delivery and that further strategies are needed to prevent perinatal transmiss ion in women with high or increasing virus levels and/or zidovudine-re sistant virus.