Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load
Dickover, R.E.; Garratty, E.M.; Herman, S.A.; Sim, M.S.; Plaeger, S.; Boyer, P.J.; Keller, M.; Deveikis, A.; Stiehm, E.R.; Bryson, Y.J.
JAMA 275(8): 599-605
1996
ISSN/ISBN: 0098-7484 PMID: 8594240 Document Number: 459440
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 50000 copies per milliliter at delivery than nontransmitting mothers (15 (75.0%) of 20 transmitters vs four (5.3%) of 75 nontransmitters; P lt .001). None of the 63 women with less than 20000 HIV-1 RNA copies per milliliter transmitted. Twenty-two women treated with open-label oral zidovudine during gestation showed an eight-fold median decrease in plasma RNA levels (median (25th and 75th percentile), 43043 (5699 and 63053) copies per milliliter before zidovudine vs 4238 (603 and 5116) HIV-1 RNA copies per milliliter at delivery; P lt .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.