HIV Drug Combination Blocks Mother-to-Child Transmission

A large clinical trial conducted in sub-Saharan Africa and India found that administering HIV-infected mothers with a 3-drug antiretroviral regimen while breastfeeding eliminated mother-to-child HIV transmission.

Findings from the ongoing Promoting Maternal and Infant Survival Everywhere (PROMISE) study support World Health Organization (WHO) guidelines that recommend all HIV-infected pregnant and breastfeeding women to have lifelong antiretroviral therapy. PROMISE, funded by the National Institutes of Health, found that daily infant nevirapine and a 3-drug maternal antiretroviral therapy was both safe and effective in the prevention of HIV transmission during breastfeeding.

The findings were presented in a poster at the 21st International AIDS Conference in Durban, South Africa, and the pre-conference 8th International Workshop on HIV Pediatrics.

“These findings add to the considerable body of evidence confirming the benefits of antiretroviral therapy for every person living with HIV,” said Anthony S. Fauci, director of the NIH National Institute of Allergy and Infectious Diseases. “Maternal antiretroviral therapy safely minimized the threat of HIV transmission through breast milk while preserving the health advantages of breastfeeding, as the high infant survival in this study underscores.”

PROMISE is a multi-component study to determine the best method to safely reduce the risk of HIV transmission from mothers to babies during pregnancy, delivery, and after childbirth, while also preserving their health. In 2014, researchers identified the superiority of a 3-drug regimen over others for preventing perinatal HIV transmission during pregnancy and birth.

From a component of the PROMISE study, researchers compared the safety and efficacy of 2 antiretroviral regimens in HIV transmission between mother and child during breastfeeding. For the study, researchers enrolled 2431 pairs of HIV-infected mothers and their HIV-negative infants at clinical research sites in India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe between June 2011 and October 2014.

On average, the women were asymptomatic and had relatively high CD4+ cell levels. HIV-positive mothers and their babies were randomized to receive either triple-drug antiretroviral therapy for the mother that continued through the follow-up study period, along with daily doses of nevirapine for their infant until 6 weeks after birth; or they were administered a triple-drug antiretroviral therapy for the mother until 1 week after delivery, and daily doses of nevirapine for the infant that started from the first week after birth and continued through the completion of study follow-up.

Researchers followed the participants for 18 months, or until the mother stopped breastfeeding, whichever came first. The results of the study found that mothers who took the triple-drug antiretroviral therapy and their infants who took nevirapine were protected from mother-to-child HIV transmission. The rate of perinatal transmission was found to be very low with 0.3% at 6-months-old, and 0.6% at 1-year-old, and did not differ between the 2 study arms.

Adverse events in the mothers and their babies occurred in low rates and were similar among the 2 arms. Although the infant mortality in resource-limited countries can be high, the findings found that nearly 99% of the babies lived to see their first birthday.

“The PROMISE team and the PROMISE mothers were gratified with the extremely low rates of infant infection and excellent infant survival with the use of maternal antiretroviral therapy,” said protocol chair Mary Glenn Fowler, MD, MPH. “These results show the importance of mothers continuing to take antiretroviral therapy to reduce the risk of mother-to-child transmission during breastfeeding.”

The findings also showed that infant nevirapine provides a safe and effective alternative if a mother has difficulty adhering to, or tolerating, antiretroviral therapy, the authors noted.

“HIV-infected mothers in low and middle income countries, who may not have access to alternative feeding methods, can be reassured that breastfeeding is a safe option for their infants,” said researcher Nahida Chakhtoura, MD.

In a different component of PROMISE, 1652 HIV-positive non-breastfeeding women who had relatively healthy immune systems were enrolled in the study and randomized to either continue antiretroviral therapy, or stop antiretroviral therapy postpartum.

The findings revealed similarly low rates of AIDS-defining and serious non-AIDS events in both groups, and other HIV-related illnesses were significantly lower among women who continued on antiretroviral therapy. The findings provide additional evidence of the benefit of antiretroviral therapy in women.