Perinatal HIV transmission refers to HIV transmission from mother to child during pregnancy, labor and delivery, or breastfeeding. It accounts for the majority of childhood HIV infections. However, since the mid-1990s, implementation of HIV testing and preventive interventions has resulted in a more than 90 percent decrease in the number of children perinatally infected with HIV in the United States, according to CDC. NIAID research has helped pave the way for development of strategies to prevent perinatal transmission both in high-resource countries like the United States and in resource-limited settings around the world.
Antiretroviral Therapy Prevents Perinatal Transmission
In 1994, results from the landmark Pediatric AIDS Clinical Trials Group (PACTG) 076 study, co-sponsored by NIAID, demonstrated that giving the drug zidovudine to pregnant women living with HIV who had little or no prior antiretroviral therapy reduced the risk of perinatal transmission by two-thirds. Researchers gave pregnant women living with HIV in the United States and France daily oral zidovudine during pregnancy and intravenous zidovudine during labor. In addition, their newborns received oral doses of the drug every six hours for the first six weeks of life.
Since the release of the PACTG 076 results, researchers have continued to develop antiretroviral drug regimens to prevent perinatal transmission. Numerous studies have demonstrated varying degrees of efficacy for a variety of antiretroviral therapy regimens, including nearly all classes of antiretroviral agents.
Receiving combined antiretroviral therapy currently is standard care for pregnant women in the United States, and therapy is recommended to begin as soon as women are diagnosed with HIV infection. Coupled with avoidance of breastfeeding and good access to HIV and pregnancy care services, these regimens can reduce perinatal transmission to less than 1 percent, according to CDC.
Reducing Perinatal Transmission in Resource-Limited Settings
Efforts in resource-limited settings to introduce antiretroviral agents for perinatal prevention have resulted in a marked decrease in perinatal HIV transmission. Although numerous challenges remain, 7 out of 10 pregnant women living with HIV worldwide receive antiretroviral drugs, according to the World Health Organization (WHO). NIAID-funded studies have helped identify antiretroviral drug regimens that are effective, affordable, and relatively easy to administer in resource-limited settings.
Breastfeeding effectively reduces infant mortality in resource-limited settings that lack safe, clean water. Antibodies from the mother’s breast milk help protect babies against potentially life-threatening diarrheal and respiratory infections. To completely protect infants from HIV transmission through breast milk, total avoidance of breastfeeding is recommended for women living with HIV in the United States and other developed countries where safe and affordable formula is available and the risk of infant mortality due to infections is low. In resource-limited settings, however, scientists are investigating perinatal HIV prevention strategies that safely minimize the threat of HIV transmission through breast milk while preserving the health benefits of extended breastfeeding. For example, in 1999, results from the NIAID-sponsored HIVNET 012 study in Uganda showed that a single dose of nevirapine given to mothers living with HIV at the onset of labor and another to their infants soon after birth reduced perinatal transmission in a breastfeeding population more effectively than a similar course of zidovudine. While these findings offered a simple, inexpensive treatment, numerous other studies have been conducted since then, and single-dose nevirapine is no longer used.
The NIAID-funded Six-Week Extended Nevirapine (SWEN) studies, conducted in Ethiopia, India, and Uganda, found that giving uninfected infants born to mothers living with HIV a regimen of nevirapine for the first six weeks of life cut the rate of HIV transmission by breastfeeding by almost half when compared with a single dose of nevirapine given at birth. Moreover, at six months, the risk of postnatal HIV infection or death for babies who received nevirapine for six weeks was nearly one-third less than that for infants given only a single dose. The PEPI-Malawi study, sponsored by NIH’s National Institute of Child Health and Human Development and CDC, found that giving nevirapine daily to breastfeeding infants from 7 days to 14 weeks of age cut the rate of HIV transmission by half for up to nine months.
Longer nevirapine regimens may offer even greater benefits. Findings from the HPTN 046 study, co-funded by NIAID and other NIH institutes, suggest that giving breastfeeding infants of mothers living with HIV a daily dose of nevirapine for six months halved the risk of HIV transmission to the infants at six months of age compared with giving infants the drug daily for six weeks.
These and other studies contributed to WHO recommendations that can help prevent perinatal transmission while allowing women living with HIV in resource-limited settings to breastfeed their infants safely.
Identifying Optimal Strategies to Prevent Perinatal Transmission
In 2010, NIAID helped launch the PROMISE study, a multinational clinical trial that aims to determine the optimal antiretroviral regimen for reducing HIV transmission during pregnancy and breastfeeding and preserving the health of both mother and child. The study is being conducted in both high- and low-resource countries.
In late 2014, NIAID announced interim results from the PROMISE study. The findings strongly support the recommendation by WHO and most countries to provide a three-drug anti-HIV regimen to all pregnant women with HIV infection.
PROMISE compared a regimen of zidovudine given as early as 14 weeks into the pregnancy, a single dose of nevirapine during labor, and two weeks of tenofovir and emtricitabine after delivery (part of the WHO “Option A” regimen) with giving women one of two triple antiretroviral drug regimens (part of the WHO “Option B and Option B+” regimens). Only 0.5 to 0.6 percent of infants whose mothers received the triple-drug combinations in Option B/B+ became infected with HIV, while 1.8 percent of infants whose mothers received Option A became infected.
The PROMISE study is ongoing, and NIAID continues to support and conduct research to identify the best ways to prevent perinatal HIV transmission while assuring the benefits of antiretroviral therapy for mother and baby.