Download Article PDF/SlidesThe risk of MTCT can be reduced to below 2% by employing interventions that include antiretroviral therapy given to HIV-infected women during pregnancy and labor, as well as to exposed infants during the first weeks of life; the avoidance of breastfeeding; and delivery by elective Caesarean section. With all of these approaches, there are numerous questions and considerations. In turn, PRN invited Dr. Elaine Abrams—a Columbia University pediatrician involved in both national and international programs focused on curtailing MTCT of HIV—to put these questions and considerations into context for the PRN membership and readers of The PRN Notebook.
| Risk Factors for MTCT | Top of page |
As for obstetrical factors, Dr. Abrams explained that prolonged rupture of membranes, defined as longer than four hours, has been associated with an increased risk of transmission. Caesarean section has been shown to be protective if electively done prior to the onset of labor. “C-sections remain protective in the context of antiretroviral therapy given for perinatal prevention, particularly zidovudine monotherapy. This procedure is recommended in the United States for HIV-positive pregnant women with viral loads greater than 1,000 copies/mL. However, C-sections may not have an added benefit when viremia is very low or undetectable as a result of using combination antiretroviral therapy.”
Infants born prematurely are also at higher risk for infection. “It was initially believed that HIV infection of the fetus led to premature delivery,” recalled Dr. Abrams, “but it appears the premature babies are at greater risk for infection during labor and delivery, compared to babies who reach full term.”
Guidelines in the United States and most European countries have strongly warned against breastfeeding among new HIV-positive mothers. However, in many parts of the world, where the benefits of breastfeeding are weighed heavily against the risks, it remains a major issue. “It has been estimated that there are about ten cases of infection for every 100 women who breastfeed for a year and that the risk of transmission is pretty constant throughout the duration of breastfeeding,” Dr. Abrams explained. “And much like the transmission of HIV in utero or around the time of labor and delivery, maternal factors—such as high viral load and low CD4+ cell counts—can increase the risk of transmission while breastfeeding.”
| Nevirapine to the Fore | Top of page |
“HIVNET 012 was an extremely important study,” commented Dr. Abrams. “It helped galvanize efforts to set up simple and cheap perinatal prevention programs in some of the poorest parts of the world. Since this study was published, the Elizabeth Glaser Pediatric AIDS Foundation, working with governments, healthcare providers, ministries, provinces, and individuals—a whole assortment of groups and individuals—has actively set up programs using single-dose nevirapine in more than 17 countries. They estimate that more than a million women have received single-dose nevirapine since these programs went into effect. We’ve also seen many governments develop national plans to roll out single-dose nevirapine for perinatal prevention.”
While the results of HIVNET 012 solidified the importance of nevirapine as an agent to help prevent perinatal HIV transmission, the infection rates were still higher than those seen in PACTG 076 and significantly higher than the transmission rates seen today in the United States in association with the use of combination antiretroviral therapy. In turn, the PHPT group—responsible for the study evaluating varying courses of zidovudine in HIV-infected pregnant women and infants discussed above—conducted a second study (dubbed PHPT-2) to examine whether adding a single dose of nevirapine to a short-course zidovudine could help further reduce MTCT HIV transmission rates (Lallemant, 2004).
Between January 2001 and February 2004, the study randomized 1,844 HIV-positive women to one of three treatment groups: zidovudine alone, started at 28 weeks’ gestation and continued through labor, delivery, and to the infant for six weeks after birth (placebo-placebo group); zidovudine plus single-dose nevirapine (200 mg) given to the woman at the onset of labor but not the infant (NVP-placebo group); or zidovudine plus single-dose nevirapine given to the woman at the onset of labor and to the infant after birth (NVP-NVP group). All women formula fed their infants after delivery. An interim analysis conducted in May 2002, involving the first 629 infants born in the study, demonstrated a significant reduction in vertical transmission in all NVP-treated mothers. In turn, the placebo-placebo group was dropped.
In the intent-to-treat analysis conducted in May 2002, a significant reduction in vertical transmission was seen in the NVP-NVP group compared with the placebo-placebo group (1.1% vs. 6.3% transmission rate respectively). In the NVP-placebo group, the rate was 2.1%. As for the final intent-to-treat analysis, the transmission rate among those in the NVP-NVP group was 2.0%, compared to a transmission rate of 2.8% in the NVP-placebo group. Results were similar in the as-treated analysis.
“What’s so important about these transmission rates in this non-breastfeeding population is that they parallel what we’re seeing in the U.S. and Europe, using much more complicated regimens with much more frequent and greater toxicities,” Dr. Abrams said. “This combined regimen does offer a more simplified and less toxic regimen that we can move forward with in resource-poor areas.”
| Conclusion | Top of page |
The second priority should be to maintain MTCT prevention programs using single-dose nevirapine. “These are often the first programs established in settings that really have never provided any form of HIV care and have virtually nothing to offer women and their families,” Dr. Abrams said. “We have to look at these programs as a starting point… as a way to train people… as a way to begin offering communities some focus on care and treatment, while also being able to decrease the rate of perinatal HIV transmission. With this groundwork, programs can be built up to a point where they can offer more comprehensive services to women who are eligible for more complex regimens that are more efficacious than single-dose nevirapine.”
| References | Top of page |
