By Liz Highleyman

A single dose of nevirapine (Viramune) administered to both mother and infant can decrease mother-to-child HIV transmission by nearly 50%, comparable to the risk reduction achieved with ultra-short course AZT (zidovudine; Retrovir). However, there is limited data about the benefits of combining single-dose nevirapine and short-course AZT.

As reported in the January 1, 2007 issue of Clinical Infectious Diseases, researchers conducted a randomized, double-blind, placebo-controlled trial to determine whether ultra-short course AZT combined with single-dose nevirapine improved neonatal outcomes compared with single-dose nevirapine alone.

Pregnant women in Zimbabwe (n = 1140) were randomly assigned to 1 of 2 treatment groups. Those in the ultra-short course AZT plus single-dose nevirapine group received a loading dose of AZT (600 mg administered orally) and continued to receive 300 mg doses of AZT orally every 3 hours while in labor; their infants received an oral AZT dosage of 2 mg/kg of body weight 4 times per day for 72 hours after birth. Mothers and infants in the single-dose nevirapine group received an AZT placebo dosed in the same manner. All mothers received oral nevirapine at a dosage of 200 mg while in labor; all infants received oral nevirapine 2 mg/kg of body weight within 72 hours after delivery.

Results

• Outcomes at 6 weeks of age were available for 609 infants.

• The primary endpoint of detectable HIV RNA or death occurred in 21.8% of infants in the ultra-short course AZT plus single-dose nevirapine arm compared with 23.6% of the infants in the nevirapine-only arm.

• Infant mortality rates were 7.4% for infants in the combination AZT/nevirapine group compared with 7.1% for those in the nevirapine-only group.

• There were 9 maternal deaths out of 596 in the combination therapy arm compared with 13 out of 571 in the nevirapine-only arm.

• The study was stopped early "on the basis of futility" after interim data showed that, with the present trends, the combined regimen would not demonstrate superiority.

Conclusion

In conclusion, the investigators wrote, "Ultra-short course AZT, when added to a standard 2-dose regimen of single-dose nevirapine, did not demonstrate a clinically important decrease in the combined end-point of mother-to-child transmission or infant death."

However, they added that high rates of adverse maternal and infant outcomes in both study arms remain a concern and "suggest that improved approaches are necessary."

1/19/07

Reference
P Thistle, R F Spitzer, R H Glazier, and others. 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. Clinical Infectious Diseases 44(1): 111-119. January 1, 2007.