Adding the drug nevirapine to the regimen given to newborns of women diagnosed with HIV shortly before or during labor halves the newborns' risk of contracting the virus, according to findings by a National Institutes of Health research network.
The researchers found that the rate of mother-to-child HIV transmission around the time of delivery was 2.2 percent among infants who received the standard drug zidovudine combined with nevirapine, compared with 4.8 percent among infants treated with zidovudine alone.
The researchers also found a reduced rate of transmission (2.4 percent) among infants treated with a three-drug combination: zidovudine, nelfinavir and lamivudine.
However, infants given the two-drug combination were less likely to have neutropenia than were those on the three drug regimen. (Neutropenia is a blood disorder consisting of low levels of neutrophils, a type of infection fighting white blood cell.) The two drug combination is also less expensive and easier to administer than the three drug combination.
"Pregnant women who don't know they have HIV or those who don't come in for prenatal care may not get the early treatment needed to keep the virus from being passed on to the baby," said study author Heather Watts, M.D., of the Pediatric, Adolescent and Maternal AIDS Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). "Our findings show that even in these situations, many, many infant cases of HIV can be prevented with the two drug combination treatment."
First author Karin Nielsen-Saines, M.D., of the University of California, Los Angeles, School of Medicine conducted the research with Dr. Mofenson and 25 colleagues at the NICHD and 17 other hospitals and research institutions in Argentina, Brazil, South Africa and the United States.
The researchers conducted the study as part of the NICHD- and NIAID-funded International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) and its predecessor networks, the HIV Prevention Trials Network (HPTN) and the Pediatric AIDS Clinical Trials Group (PACTG). Additional support for IMPAACT was provided by NIH's National Institute of Mental Health.
Their findings appear in the New England Journal of Medicine.
The study included more than 1,600 infants born between 2004 and 2010. All had received one of three treatments:
• the standard twice daily zidovudine alone for six weeks,
• twice daily zidovudine for six weeks plus three doses of nevirapine in the first six days after birth
• twice daily zidovudine for six weeks plus two weeks of treatment with nelfinavir and lamivudine. Newborns are most susceptible to HIV in the two weeks following birth.
To reduce the risk of HIV transmission through breast milk, mothers were counseled to formula feed their infants. The researchers tested the infant's HIV status at three months. About 8 percent of all the infants were HIV positive.
Within 48 hours after birth, the researchers tested the infants for HIV. Overall, about 6 percent tested positive, indicating that infection occurred before birth.
The researchers calculated the overall infection rates for all the infants in the study - those infected at birth, and later, after 6 weeks of treatment. In addition to acquiring HIV during their time in the womb, infants may also become infected during the labor and delivery process.
The study evaluated the effectiveness of the treatments in reducing HIV transmission during this latter interval (intrapartum transmission). So the researchers calculated the transmission rate around the time of delivery - the proportion of infections among infants who tested negative at birth, but later tested positive after six weeks of treatment.
In the different drug treatment groups, infection rates were 7.1 percent in the zidovudine-nevirapine group (which had a 2.2 percent transmission rate), 7.4 percent in the three-drug arm (which had a 2.4 percent transmission rate), and 11 percent in the zidovudine-only group (which had a 4.8 percent transmission rate).
The researchers also found that mothers with more severe HIV infections were more likely to transmit HIV to their infants than were other mothers in the study. Illegal drug use during pregnancy also increased the transmission rate.
"The two-drug combination is relatively easy to administer and well tolerated by the babies," Dr. Watts said. "Now that this alternative has been shown to be effective, it is increasingly being adopted worldwide to prevent transmission in these high-risk situations."