Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial.
BACKGROUND
In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age.


METHODS
From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat.


RESULTS
We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10.3% and 8.1% at birth (p=0.35); 20.0% and 11.8% by age 6-8 weeks (p=0.0063); 22.1% and 13.5% by age 14-16 weeks (p=0.0064); and 25.8% and 15.7% by age 18 months (p=0.0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects.


CONCLUSIONS
Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8.2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10.1% [95% CI 3.5-16.6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007745:Labor Onset / Q000187:drug effects; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D014454:Uganda; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine; D019829:Nevirapine