A randomized, double-blind, placebo-controlled trial of combined nevirapine and zidovudine compared with nevirapine alone in the prevention of perinatal transmission of HIV in Zimbabwe.
BACKGROUND
A single dose of nevirapine (sdNVP) administered to both mother and infant can decrease mother-to-child transmission of human immunodeficiency virus (HIV) by 47%, compared with ultra-short course zidovudine therapy (usZDV). There is limited data about the benefit of usZDV added to sdNVP to prevent mother-to-child transmission.


METHODS
We performed a double-blind, randomized, placebo-controlled trial to determine whether usZDV combined with sdNVP improved neonatal outcome, compared with sdNVP alone. Mothers were randomized to 1 of 2 treatment groups. Mothers in the usZDV/sdNVP group received a loading dose of zidovudine (600 mg administered orally) and continued to receive 300-mg doses of zidovudine orally every 3 h while in labor, and their infants received zidovudine at a dosage of 2 mg per kg of body weight 4 times per day orally for 72 h. Mothers and infants in the sdNVP group received zidovudine placebo dosed in the same manner. All mothers also received nevirapine at a dosage of 200 mg orally while in labor, and all infants received nevirapine 2 mg per kg of body weight orally within 72 h of delivery.


RESULTS
The study was stopped on the basis of futility, because interim data showed that, at present trends, superiority would not be demonstrated. Results at 6 weeks of age were available for 609 infants. The primary end point of HIV RNA positivity or death occurred in 21.8% of infants in the usZDV/sdNVP arm and 23.6% of the infants in the sdNVP arm.


CONCLUSIONS
usZDV, when added to a standard 2-dose regimen of sdNVP, did not demonstrate a clinically important decrease in the combined end point of mother-to-child transmission or infant death. High rates of adverse maternal and infant outcome in both study arms suggest that improved approaches are necessary.
Thistle
Paul
P
The Salvation Army Howard Hospital, Glendale, Zimbabwe.
Spitzer
Rachel F
RF
Glazier
Richard H
RH
Pilon
Richard
R
Arbess
Gordon
G
Simor
Andrew
A
Boyle
Eleanor
E
Chitsike
Inam
I
Chipato
Tsungai
T
Gottesman
Maureen
M
Silverman
Michael
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology; D011256:Pregnancy Outcome; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use; D015030:Zimbabwe
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine