Postnatal antiretroviral prophylaxis may reduce risk for HIV transmission

Addition of zidovudine did not improve results over nevirapine alone.

Issue: March 2008

Daily antiretroviral prophylaxis with nevirapine or nevirapine plus zidovudine for the first 14 weeks after birth significantly reduced the risk for postnatal HIV infection at age 9 months compared with treatment for only one week. HIV-free survival was also significantly increased.

“In sub-Saharan Africa, breast-feeding contributes to about 8% to 16% of postnatal HIV transmission,” said Taha E. Taha, MD, a professor of epidemiology at the Johns Hopkins University Bloomberg School of Public Health in Baltimore. “We know that preventive measures are urgently needed to reduce breast-milk associated HIV transmission and improve child survival.”

The Post Exposure Prophylaxis of Infants-Malawi study was a randomized, open-label, phase-3 trial of 14-week extended infant antiretroviral prophylaxis in children born to HIV-positive mothers in Blantyre, Malawi. Taha presented the results at The 15th Conference on Retroviruses and Opportunistic Infections, held recently in Boston.

Study treatments

The control arm of the study received a single dose of nevirapine plus one week of zidovudine. There were two extended prophylaxis arms of the study: in one arm, infants were treated with the same initial regimen followed by nevirapine to age 14 weeks; in the other, the same initial regimen was followed by nevirapine plus zidovudine to age 14 weeks. Mothers were counseled to breastfeed exclusively and wean by 6 months.

The researchers enrolled 3,276 infants; excluding those who were infected at birth, the control arm had 1,003 infants, the nevirapine arm had 1,016 infants, and the nevirapine plus zidovudine arm had 997 infants. “The baseline characteristics by treatment arm were comparable, for both mother and infant factors,” Taha said.

After 9 months, infants in the control group had about a 10.6% probability of HIV-1 infection. The nevirapine group had a 5.2% probability, and the nevirapine plus zidovudine group had a 6.4% probability. “Starting from six weeks, there was clear suppression,” Taha said. He noted that the differences between the control and the two treatment groups were statistically significant out to 18 months.

Infant mortality

The probability of death in infants was not significantly different at any time point during the study. However, “the estimates of mortality within the control arm were slightly higher,” Taha said. At 9 months, the probability of death in the control arm was 8.9% compared with 6.8% in the nevirapine arm and 6.3% in the nevirapine plus zidovudine arm.

The researchers also analyzed a composite endpoint of HIV-1 infection or death, and found a probability at 9 months of 16.8% in the control arm compared with 10.6% in the nevirapine group and 11.2% in the nevirapine plus zidovudine group. This was a statistically significant difference for both treatment groups up to 9 months vs. the control arm, and the nevirapine group was significantly better than the control up to 15 months.

After adjustment for other risk factors, the extended treatments reduced the risk for HIV infection. The hazard ratio for nevirapine vs. control was 0.56 (95% CI, 0.41-0.76), and the HR for nevirapine plus zidovudine vs. control was 0.65 (95% CI, 0.48-0.88). Maternal CD4 count decreases of 100 units resulted in a HR of 1.27 (95% CI, 1.19-1.36).

Similar results were found for the risk factors associated with HIV infection or mortality. For the nevirapine arm vs. control, the HR was 0.69 (95% CI, 0.55-0.87); for the nevirapine plus zidovudine arm vs. control, the HR was 0.72 (95% CI, 0.57-0.90). Maternal CD4 count decreases were again associated with an increase in risk, with an HR of 1.14 (95% CI, 1.09-1.19).

Treatment toxicity

Overall, there were no significant differences between the groups regarding to serious adverse events, and most of the serious events were not related to the study treatment. Taha said that there were more serious adverse events deemed to be possibly related to the treatments in the nevirapine plus zidovudine arm than in the control group.

“Extended infant prophylaxis for 14 weeks reduces HIV transmission and improves HIV-free survival in breastfed infants,” Taha said. “The efficacy was maintained at more than 50% through nine months but decreases through time with continued breast-feeding.” – Dave Levitan

For more information:

Taha T, Thigpen M, Kumwenda N, et al. Extended infant post-exposure prophylaxis with antiretroviral drugs significantly reduces postnatal HIV transmission: the PEPI-Malawi study. #42. Presented at: The 15th Conference on Retroviruses and Opportunistic Infections; Feb. 3-6, 2008; Boston.