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.


METHODS
A nonrandomized prospective cohort study.


METHODS
University medical center and two general hospital affiliates from May 1989 to September 1994.


METHODS
Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants.


METHODS
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.


METHODS
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 < .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 eightfold 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 < .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.
Dickover
R E
RE
Department of Pediatrics, UCLA School of Medicine 90024, USA.
Garratty
E M
EM
Herman
S A
SA
Sim
M S
MS
Plaeger
S
S
Boyer
P J
PJ
Keller
M
M
Deveikis
A
A
Stiehm
E R
ER
Bryson
Y J
YJ
D015492:AIDS Serodiagnosis / Q000379:methods; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D036861:Delivery, Obstetric; D004352:Drug Resistance, Microbial; D005260:Female; D005865:Gestational Age; D015658:HIV Infections / Q000097:blood / Q000151:congenital / Q000188:drug therapy / Q000635:transmission*; D006679:HIV Seropositivity / Q000097:blood / Q000151:congenital / Q000188:drug therapy / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D012306:Risk; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*
D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D015215:Zidovudine