July 12, 2002
Dr. Le Coeur presented the preliminary results of the PHPT-2 study evaluating whether the addition of nevirapine (NVP) during labor and given to the infant reduces the transmission of HIV from the mother to child. This is a multi-center, double-blinded, three-arm study conducted in Thailand.
Mothers had to start ZDV 300 mg twice daily at 28 weeks gestation or as soon as possible thereafter. Mothers had to also agree to formula feed their infants. The three arms are as follows: 1) NVP + ZDV mother/NVP + ZDV infant, 2) NVP + ZDV mother/Placebo + ZDV infant and 3) Placebo + ZDV mother/Placebo + ZDV infant. All mothers were given ZDV during labor. ZDV was given for one week to infants or six weeks to the infant if the mother had been on ZDV less than four weeks prior to delivery.
NVP was given as a single 200 mg oral dose to the mother at onset of labor and the infant was given 6 mg orally 48-72 hours after birth. The primary endpoint was the number of infants HIV infected as determined by two positive HIV-1 RNA PCRs obtained on different samples. A total of 1,313 women have been enrolled, 48 percent started ZDV at 28 weeks, 16 percent after 32 weeks. Baseline CD4+ T-cell count was 371 cells/µl and HIV viral load was 3.94 log copies/ml. There have been 922 deliveries with 629 evaluable infants. Twenty-one percent had non-elective cesarean sections.
The Data Safety Monitoring Board recommended that the ZDV alone arm be stopped -- because HIV transmission was significantly higher than in the NVP + ZDV mother/NVP + ZDV infant arm (stopping boundary: P = 0.00036) -- and that the other two arms be continued. Although Dr. Le Coeur reported that adding NVP during labor and in the neonate in addition to oral ZDV prophylaxis starting at 28 weeks or as soon as possible thereafter significantly decreases the risk of HIV perinatal transmission, she did not give the actual numbers of infected infants born in any of the three arms.
One of the important follow up concerns will be the emergence of NVP resistance among the mothers and the infected infants. Also of concern is that the mothers were given a single dose of NVP and there was no intent to continue the therapy which will ultimately lead to progressive HIV disease among the mothers. So, as much as we may be preventing some of these infants from acquiring HIV, they will most likely grow up to be orphans and subsequent care of this generation is unknown.
Although this is a start to assist other countries in preventing HIV, we need to do so responsibly. We do know that potent antiretroviral therapy will reduce vertical transmission so one can make a strong argument that studies like these are unethical unless one can assure continued therapy to the mothers and their infected infants.
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