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ARTICLE |

Identification of Levels of Maternal HIV-1 RNA Associated With Risk of Perinatal Transmission:  Effect of Maternal Zidovudine Treatment on Viral Load

Ruth E. Dickover, PhD; Eileen M. Garratty, AIBMS; Steven A. Herman, PhD; Myung-Shin Sim, MS; Susan Plaeger, PhD; Pamela J. Boyer, MD, PhD; Margaret Keller, MD; Audra Deveikis, MD; E. Richard Stiehm, MD; Yvonne J. Bryson, MD
JAMA. 1996;275(8):599-605. doi:10.1001/jama.1996.03530320023029.
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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<.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], 43043 [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.(JAMA. 1996;275:599-605)

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