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 immunodeficienc y virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treat ment reduces perinatal transmission. Design. - A nonrandomized prospec tive cohort study, Setting. - University medical center and two genera l hospital affiliates from May 1989 to September 1994. Patients. - Nin ety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants . Intervention. - forty-two mothers (43 pregnancies) received zidovudi ne therapy during pregnancy and/or during labor and delivery. Eleven i nfants received prophylactic zidovudine for the first 6 weeks after de livery. 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 lev els higher than 50 000 copies per milliliter at delivery than nontrans mitting mothers (15 [75.0%] of 20 transmitters vs four [5.3%] of 75 no ntransmitters; P<.001). None of the 63 women with less than 20 000 HIV -1 RNA copies per milliliter transmitted. Twenty-two women treated wit h open-label oral zidovudine during gestation showed an eightfold medi an decrease in plasma RNA levels (median [25th and 75th percentile], 4 3 043 [5699 and 63 053] copies per milliliter before zidovudine vs 423 8 [603 and 5116] HIV-1 RNA copies per milliliter at delivery; P<.001), and none transmitted. Four zidovudine-treated women with high HIV-1 l evels transmitted despite the presence of zidovudine-sensitive virus i n vitro in both the mothers and their infants. Conclusions. - Maternal HIV-1 RNA levels were highly predictive of perinatal transmission ris k and suggest that certain levels of virus late in gestation and/or du ring 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 perinat al transmission in women with high or increasing virus levels and/or z idovudine-resistant virus.