Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: a randomized controlled trial.
BACKGROUND
Antenatal counseling and human immunodeficiency virus (HIV) testing are not universal in Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012 nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant within 72 hours of birth).


OBJECTIVE
To determine risk of mother-to-child transmission of HIV when either standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women tested at delivery.


METHODS
A randomized, open-label, phase 3 trial conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were previously antiretroviral treatment-naive. Infants were randomly assigned to NVP (n = 448) and NVP plus ZDV (n = 446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18 months. The HIV status of 90% of all infants was established at 6 to 8 weeks.


METHODS
Mothers received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week.


METHODS
HIV infection of infant at birth and 6 to 8 weeks, and adverse events.


RESULTS
The mother-to-child transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in those administered NVP plus ZDV (P =.30). A life table estimate of transmission at 6 to 8 weeks was 14.1% (95% confidence interval [CI], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%-19.8%) in those who received NVP plus ZDV (P =.36). For infants not infected at birth and retested at 6 to 8 weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who received NVP plus ZDV (P =.88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks. Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving NVP only and NVP plus ZDV, respectively (P =.76).


CONCLUSIONS
The frequency of mother-to-child HIV transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing neonatal ZDV was similar to that of a standard NVP regimen.
Taha
Taha E
TE
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md 21205, USA. ttaha@jhsph.edu
Kumwenda
Newton I
NI
Hoover
Donald R
DR
Fiscus
Susan A
SA
Kafulafula
George
G
Nkhoma
Chiwawa
C
Nour
Samah
S
Chen
Shu
S
Liomba
George
G
Miotti
Paolo G
PG
Broadhead
Robin L
RL
D015492:AIDS Serodiagnosis; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D036861:Delivery, Obstetric; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000151:congenital* / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008295:Malawi; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D016019:Survival Analysis; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine; D019829:Nevirapine