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Andrew B. Kairalla MD, Editor
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Prevention of HIV Transmission
Single-Dose Perinatal Nevirapine plus Standard Zidovudine to Prevent Mother-to-Child Transmission of HIV-1 in Thailand. Lallemant M, Jourdain G, Le Coeur S, et al. NEJM (July 15, 2004) 351: 271-228.
Background Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV.
Methods We conducted a randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of nevirapine (nevirapine–nevirapine regimen); in another, mothers and infants received nevirapine and placebo, respectively (nevirapine–placebo regimen); and in the last, mothers and infants received placebo (placebo–placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed. The end point of the study was infection with HIV in the infants, established by virologic testing.
Results Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first interim analysis, the independent data monitoring committee stopped enrollment in the placebo–placebo group. Among women who delivered before the interim analysis, the as-randomized Kaplan–Meier estimates of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapine–nevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo–placebo group (P<0.001). The final per-protocol transmission rate in the nevirapine–nevirapine group, 1.9 percent (95 percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine–placebo group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated with nevirapine therapy.
Comment. These results were so dramatic, that it prompted an
early release of this article by NEJM. It appears that we now have a new
standard for preventing perinatal transmission of HIV. In addition to
standard treatment of mother and baby with zidovudine (starting at 28 weeks
gestation), we can now add a single dose (200 mg) of nevirapine to mother at
the onset of labor, and a single dose (6 mg) of nevirapine to baby at 48-72
hours. Adding nevirapine takes the risk of perinatal transmission of HIV down
to less than 2%, versus 6.3% with zidovudine alone. While there was no
statistical difference between giving nevirapine to mother alone (2.8%
transmission rate) vs. treating both mother and baby (1.9% transmission
rate), there seems to be little downside to treating the baby as well. No
significant side effects attributed to the drug was reported. The most common
side effect was a rash (4% of mothers and 16% in babies). One potential risk
for mothers was that a single intrapartum dose of nevirapine could induce drug
resistance mutations making later treatment with this drug less effective.
ABK.
Date: 16 Sep 2004
Time: 10:56:24
It would have been nice if they also study another group: placebo-neviparine.
This group however would not be important if our OB's add neviparine to their
HIV patients already on zidovudine treatment. Maybe we all should 'advertise'
this article to the OB's in our respective hospitals.
UserName: Felix A. Estrada, MD
Institution: Parkway Regional Medical Center
telephone: 305-654-5612
email: felixaestradamd@pol.net
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