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

An extended course of the antiretroviral drug nevirapine (NVP) helps the breastfeeding babies of HIV-infected mothers remain HIV-negative and live longer, according to several new studies presented at the 15th Conference on Retroviruses and Opportunistic Infections held in Boston from February 3–6.

Three coordinated, large-scale Phase III clinical trials sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), found that NVP given once daily to breastfeeding infants from days 8 to 42 of life cut the rate of HIV transmission via breastfeeding by almost half at 6 weeks when compared with a single dose of NVP given to infants at birth, the current standard of care. Moreover, at 6 months, the risk of postnatal HIV infection or death for babies who received NVP for six weeks was nearly one-third less than the risk for infants given only a single dose. These clinical trials are known as the Six-Week Extended NVP (SWEN) studies.

A separate study—the PEPI-Malawi study—sponsored by NIH’s National Institute of Child Health and Human Development (NICHD) and the U.S. Centers for Disease Control and Prevention (CDC) found that giving NVP 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.

According to the authors of the studies, these findings are critical because approximately 150,000 infants worldwide acquire HIV annually through breastfeeding, and the risk of HIV transmission is generally believed to be greatest during the earliest months of life. Despite that risk, the World Health Organization and UNICEF recommend that infants born to HIV-infected mothers who lack access to safe, affordable and sustainable replacement feeding should breastfeed for at least six months, because under such conditions, breastfeeding may protect infants from other causes of illness and death that pose a greater risk than HIV infection itself. Replacement feeding, early weaning or both are not options for many women and their babies for economic, cultural, and health and safety reasons.

The SWEN Studies

The NIAID-sponsored SWEN studies sought to determine whether giving an extended daily regimen of NVP to the breastfeeding babies of HIV-infected mothers would reduce the rates of HIV acquisition and death in these infants more than the standard of care alone.

Investigators from the Johns Hopkins University (JHU) and an international team of researchers enrolled nearly 2,000 mother-infant pairs in three separate but coordinated studies that began in Ethiopia in 2001, India in 2002 and Uganda in 2004. The available standard of care in these countries for preventing mother-to-child transmission during labor and delivery is a single dose of NVP to the HIV-infected mother during labor and a single dose to her baby shortly after birth. This care was offered to all the women who were screened and identified as HIV-infected. Also, all women were counseled about the potential risks of HIV transmission associated with breastfeeding.

The infants of mothers who chose to breastfeed their babies and who gave informed consent were then selected at random to receive either one of two regimens: a single dose of NVP shortly after birth and a daily multivitamin from days 8 to 42; or a single dose of NVP shortly after birth and a daily dose of NVP plus a multivitamin from days 8 to 42. (The extended treatment period was begun at day 8 because previous studies have indicated that giving infants a single dose of NVP shortly after birth protects them for several days from transmission of HIV via breastfeeding.) Data were analyzed to determine the impact of extended NVP therapy on HIV transmission and rates of infant death at 6 weeks and 6 months.

The combined rates of HIV infection and death at both 6 weeks and 6 months were significantly lower in the SWEN group than in the group that received the standard, single-dose NVP regimen alone. The risk of postnatal HIV infection or death at 6 weeks was 3.7 percent in the SWEN group, 42 percent lower than in the single-dose group. At 6 months, the risk was 8.0 percent in the SWEN group, 27 percent lower than in the single-dose group.

The SWEN studies were led by J. Brooks Jackson, M.D., M.B.A., and Laura Guay, M.D., of JHU in collaboration with co-investigators at the Makerere University/Johns Hopkins University Research Collaboration in Kampala, Uganda; by Andrea Ruff, M.D., of JHU in collaboration with co-investigators at Addis Ababa University in Addis Ababa, Ethiopia; and by Robert Bollinger, M.D., M.P.H., of JHU in collaboration with co-investigators at BJ Medical College in Pune, India.

For more information about the SWEN studies, please see the SWEN Questions and Answers.

The PEPI-Malawi Study

In a separate study co-sponsored by NICHD and CDC, investigators from JHU and the University of Malawi examined whether a 14-week course of NVP alone or in combination with another antiretroviral drug, zidovudine (AZT), could reduce HIV transmission and death in the breastfeeding infants of HIV-infected mothers more than Malawi’s current standard of care: a single dose of NVP and one week of AZT. In particular, the researchers in this post-exposure infant prophylaxis (PEPI) study set out to determine the HIV transmission rates for each of the three regimens. The scientists enrolled 3,276 mother-infant pairs in Blantyre, Malawi, from April 2004 until August 2007.

Both 14-week extended drug courses cut the rate of HIV transmission via breastfeeding in 9-month-old infants when compared with the standard of care in Malawi. The rate of HIV transmission was reduced by about 50 percent—from 10.6 percent to 5.2 percent—in infants who received the extended NVP regimen, and by about 40 percent—from 10.6 percent to 6.4 percent—in infants who received the extended NVP and AZT regimen. Further, the extended drug regimens were found to decrease the rate of HIV infection or death by more than 30 percent among the infants at 9 months. Use of NVP and AZT in combination was no more effective than NVP by itself, the researchers found.

The PEPI-Malawi study was led by Taha E. Taha, M.D., Ph.D., of JHU and Newton Kumwenda, Ph.D., of the University of Malawi College of Medicine and was conducted at Queen Elizabeth Central Hospital and five health centers in Blantyre, Malawi.

For more information about the PEPI-Malawi study, please see the PEPI-Malawi Questions and Answers.

The SWEN and PEPI-Malawi studies demonstrate that providing extended courses of daily NVP to breastfeeding infants is as safe as the current standard of care for preventing mother-to-infant transmission of HIV in the countries where the studies were conducted (single-dose NVP in the SWEN countries or single-dose NVP plus one week of infant AZT in Malawi). Based on these encouraging findings, NIAID has changed the design of a similar study that was comparing placebo to NVP for the first six months of life in infants born to HIV-infected mothers. The study has been modified so all infants receive NVP for the first six weeks of life. This Phase III clinical trial is ongoing in Uganda and Zimbabwe and planned for South Africa and Tanzania. Conducting the study 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 NICHD. .

Media inquiries can be directed to the NIAID News and Public Information Branch at 301-402-1663, niaidnews@niaid.nih.gov.

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.

NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit http://www.nichd.nih.gov.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov

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