National Institute of Allergy and Infectious Diseases (NIAID)
http://www.niaid.nih.gov/

National Institute of Child Health and Human Development (NICHD)
http://www.nichd.nih.gov/

February 6, 2008

1.		What are the Six-Week Extended Nevirapine (SWEN) studies and why were they conducted?
		The SWEN studies are three separate but coordinated large-scale Phase III clinical trials funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trials were conducted to determine whether giving HIV-negative infants of HIV-infected mothers a regimen of nevirapine (NVP) for the first 6 weeks of life reduces the risk of HIV transmission through breastfeeding more than the current standard of care: a single dose of NVP given to the mother during labor and to the infant shortly after birth.
2.		Where were the SWEN studies conducted and by whom?
		The studies were conducted in Ethiopia, India and Uganda and were led by scientists from the host countries and the Johns Hopkins University in the United States, as follows: Ethiopia, in collaboration with co-investigators at Addis Ababa University Faculty of Medicine in Addis Ababa Principal Investigator: Andrea Ruff, M.D., Johns Hopkins University, Bloomberg School of Public Health India, in collaboration with co-investigators at the BJ Medical College and National AIDS Research Institute in Pune Principal Investigator: Robert Bollinger, M.D., M.P.H., Johns Hopkins University School of Medicine Uganda, in collaboration with co-investigators at Makerere University/Johns Hopkins University Research Collaboration in Kampala and the Ugandan Ministry of Health Principal Investigators: J. Brooks Jackson, M.D., M.B.A., and Laura Guay, M.D., Johns Hopkins University School of Medicine
3.		How were these three studies designed?
		In each study, the current standard of care (one dose of NVP to the mother and one to the infant) was offered to all women who were screened and identified as HIV-infected. All of the women were counseled about the risks of HIV transmission associated with breastfeeding. The infants of the mothers who chose to breastfeed and who gave informed consent to participate were selected at random to receive either a single dose of NVP shortly after birth and a daily multivitamin from days 8 to 42 of life; or a single dose of NVP shortly after birth and a daily dose of NVP plus a multivitamin from days 8 to 42. Only the infants who were HIV-uninfected at birth were included in the analyses of the data from the clinical trials. The Ugandan study included a third group of mother-infant pairs who received HIV immune globulin in combination with the standard NVP regimen.
4.		Why did the extended course of NVP begin at day 8 rather than immediately following the first dose?
		All infants in the studies received NVP shortly after birth in keeping with the current standard of care. Because the drug generally remains in infants’ bodies for at least seven days before their systems begin to clear it, researchers began giving the babies the extended daily NVP regimen on their eighth day of life.
5.		What are the primary results of these studies?
		In all three studies, the six-week NVP regimen was found to be as safe as and more effective than single-dose NVP in reducing the rates of postnatal HIV transmission and death in breastfeeding infants born to HIV-infected women. At 6 weeks of age, the risk of HIV transmission for infants who received six-week NVP was 2.5 percent, 46 percent lower than the risk for those who received a single dose of NVP. At 6 months of age, there was no significant reduction in the risk of HIV transmission between infants who received the six-week NVP regimen and those who received the standard regimen. At 6 months of age, the risk of death was 1.1 percent for infants who received 6-week NVP and 3.6 percent for infants who received a single dose of NVP. The risk of postnatal HIV infection or death in infants who received six-week NVP compared with those who received single-dose NVP was 3.7 percent versus 6.8 percent at 6 weeks of age and 8.1 percent versus 11.6 percent at 6 months of age.
6.		Did the use of HIV immune globulin in the Ugandan study have any effect on these results?
		No. The infants who received HIV immune globulin were not included in these analyses. Those data will be analyzed separately and compared with data from the infants who received a single dose of NVP.
7.		When were these studies conducted?
		The studies began in Ethiopia in February 2001, India in August 2002, and Uganda in July 2004. The researchers completed follow-up of the infants at all three sites by fall 2007.
8.		How many mother-infant pairs were included in these studies?
		Initially, 1,964 mother-infant pairs were enrolled in the studies. Sufficient data for evaluation were available for 1,887 mother-infant pairs; 986 of these infants received single-dose NVP, and 901 received the six-week regimen.
9.		What drug or regimen is currently used to prevent mother-to-infant transmission of HIV?
		Based on the results published in 1999 of a groundbreaking NIAID-sponsored study in Uganda (HIVNET 012), one of the current standards of care used globally to reduce mother-to-child transmission of HIV during labor and delivery in resource-limited settings is a single oral dose of NVP given to an HIV-infected woman in labor and another dose given to the baby shortly after birth. This regimen was found to be more effective, more affordable and easier to administer in resource-limited settings than other regimens. There is no standard regimen for reducing the risk of HIV transmission through breastfeeding.
10.		What are the implications of these study results?
		Because the risk of HIV transmission via breastfeeding is generally believed to be higher during the earliest months of life, the findings from the SWEN studies have the potential to greatly reduce HIV transmission or death in infants while allowing HIV-infected women to breastfeed when it is the only practical option.  In addition, standard practices for preventing mother-to-infant transmission of HIV, which are based on guidelines issued by the World Health Organization and made by individual ministries of health, may be re-evaluated in light of these findings because they suggest that the breastfeeding infants of HIV-infected mothers may benefit from continuing to receive NVP for six weeks.
11.		What are the implications of these results for other ongoing or planned clinical trials studying the prevention of mother-to-child transmission of HIV?
		NIAID has changed the design of an ongoing study of HIV transmission through breastfeeding from HIV-infected mothers to babies who are born without HIV infection. This Phase III clinical trial is evaluating the safety and efficacy of a regimen of NVP given to breastfeeding infants from 6 weeks to 6 months of life. Originally, after receiving the standard single-dose NVP at birth, the infants were randomly selected to receive either a placebo or NVP for their first 6 months of life. The experiment has been modified so all infants receive NVP for the first 6 weeks of life. Conducting the trial are the HIV Prevention Trials Network, which is funded by NIAID, and the International Maternal Pediatric/Adolescent AIDS Clinical Trials Group, which is co-funded by NIAID and the National Institute of Child Health and Human Development, also part of NIH.   Other studies may take the findings of the SWEN studies into consideration and may be modified as a result.
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NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

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