Daily Nevirapine for Newborns Reduces HIV Transfer Through Breast Milk

Brian Hoyle

March 10, 2011

March 10, 2011 (Boston, Massachusetts) — Infants who receive daily nevirapine (NVP) for a full 6 months while being breastfed by their HIV-positive mothers are less apt to become HIV-positive than their counterparts who receive NVP prophylaxis for only 6 or 14 weeks.

The longer regimen is not associated with an increase in adverse events, according to the results of a phase 3 randomized placebo-controlled study presented here at the 18th Conference on Retroviruses and Opportunistic Infections.

"There have been other studies looking at the benefit of NVP for up to 6 months. However, a comparison of shorter regimens and a longer 6-month regimen has not been done in a way that has the power to detect absolute differences — statistically significant differences — in the shorter- and longer-term regimens," reported coinvestigator Yvonne Maldonado, MD, from Stanford University in Palo Alto, California, and the University of the Witwatersrand in Durban, South Africa. Dr. Maldonado presented the results for study head Hoosen Coovadia, MD, from the University of the Witwatersrand.

"These findings show that giving the infants of HIV-infected mothers an antiretroviral drug daily for the full duration of breastfeeding safely minimizes the threat of HIV transmission through breast milk while preserving the health benefits of extended breastfeeding," Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, stated in a National Institutes of Health information release concerning the study.

The HPTN 046 trial enrolled 1522 infants born to 1505 HIV-infected women in 4 regions of Africa. The infants received daily NVP for the first 6 weeks after birth. The infants who were HIV-negative at 6 weeks were randomized to receive, in a double-blind fashion, NVP (759 infants of 752 women) or placebo (763 infants of 753 women) for 6 months or the end of breastfeeding, whichever came first.

The investigators compared rates of HIV infection, safety, and tolerance of NVP in the 2 study groups.

At 6 weeks, 29% of the women in each group — 221 of the 752 women in the NVP group and 219 of the 753 women in the placebo group — were receiving highly active antiretroviral therapy (HAART). At that time, the median CD4 count of the mothers was 528 and 560 cells/mm3 in the treatment and placebo groups, respectively.

By 6 months, HAART had increased to 31% and 32% of women in the treatment and placebo groups, respectively. At 3 months, 95% of the infants in each group were being breastfed exclusively. Between 6 and 9 months, breastfeeding dropped precipitously, with more than 90% in each group no longer breastfeeding.

Self-reported compliance with the daily oral drug regimen through 6 months was 88% to 96% in both study groups.

In mothers who were receiving HAART at the time of the 6-week randomization to NVP or placebo, the 6-month HIV infection rate was 0.5% in the NVP group and 0.0% in the placebo group. This overall infection rate was 55% less than that in mothers who were not receiving HAART at randomization. At 6 months, it was 1.4% in the NVP group and 3.4% in the placebo group.

Adverse events occurred at a rate of 86% in both study groups. Serious adverse events — mostly due to infectious diseases unrelated to NVP use, including diarrhea, pneumonia, and malaria — occurred in 19% of the NVP group and 17% of the placebo group. Only 5% of the infants in either group had to stop taking NVP.

There were 43 deaths during the study period. Of these, two thirds occurred after 6 months, when most infants where no longer breastfeeding.

In women whose CD4 counts were less than 350 cells/mm3 when they delivered and who were receiving HAART, no detectable HIV was transferred through the breast milk during the course of the trial.

The highest transmission of HIV occurred in women with CD4 counts below 350 cells/mm3 who did not receive HAART, even though, under World Health Organization (WHO) guidelines, they should have. The difference was not statistically significant.

In the most striking finding, according to Dr. Maldonado, infants of mothers who had a CD4 count of 350 cells/mm3 or greater, and who therefore did not require antiretroviral therapy (according to WHO guidelines), the 6-month NVP regimen reduced breast-milk-transmitted HIV by 76%, compared with the 6-week regimen.

"This indicates that there is a group of infants that is relatively unprotected at this time," Dr. Maldonado told Medscape Medical News.

The final analysis of the data will occur in the summer of 2011, when infants have reached the 18-month follow-up.

Dr. Maldonado and Dr. Fauci have disclosed no relevant financial relationships.

18th Conference on Retroviruses and Opportunistic Infections (CROI): Late-Breaking Abstract 123. Presented March 2, 2011.

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