WASHINGTON, D.C. - A joint Uganda-U.S. study has found an effective, safe and cost-effective regimen for preventing perinatal HIV transmission.
Interim results from the study demonstrated that a single, oral dose of the antiretroviral drug nevirapine (Viramune, Roxane Laboratories) given to an HIV-infected woman in labor and another to her infant within three days of birth reduced the transmission rate by half compared with a similar short course of zidovudine (AZT, Retrovir, Glaxo Wellcome).
Uganda investigators, part of the NIAID-supported HIV Prevention Trials Network (HIVNET), opened the trial two years ago in Kampala, Uganda. Women enrolled in the study were in their ninth month of pregnancy and were treatment naive.
The randomized study, known as HIVNET 012, compared the safety and efficacy of two different short-course regimens of antiviral drugs administered late in pregnancy. The women received either a 200-mg dose of oral nevirapine at the onset of labor, followed by a 2-mg/kg oral dose given to their babies within three days of birth; or a 600-mg dose of AZT at the onset of labor, and 300-mg doses every three hours during labor. The infants born to mothers in the AZT group received 4 mg/kg given twice daily for the first week of life. Both drugs appeared to be safe and well-tolerated.
For the interim analysis, the team looked at data from 618 mothers (308 receiving AZT and 310 receiving nevirapine) and their infants. Nevirapine was markedly more effective, researchers said. At 14 to 16 weeks of age, 13.1% of infants who received nevirapine were infected with HIV, compared with 25.1% of those who received AZT.
"In this study, the short-course nevirapine regimen resulted in a 47% reduction in mother-to-infant HIV transmission compared with a short course of AZT. The implications of this study for developing countries, where 95% of the AIDS epidemic is occurring, are profound," said Brooks Jackson, MD, of Johns Hopkins University School of Medicine. Jackson was the lead U.S. investigator on the trial.
Finding affordable interventions for developing countries is key to curtailing the AIDS epidemic. In parts of sub-Saharan Africa, up to 30% of pregnant women are infected with HIV, and 25% to 35% of their infants will be born infected. UNAIDS estimated that about 1,800 HIV-infected infants are born every day in developing countries.
Several years ago, a protocol was found using AZT to prevent perinatal transmission. That regimen, used in the West, is too expensive and impractical for widespread use in poorer countries.
Based on average U.S. wholesale costs, the cost of the nevirapine regimen is much cheaper than the long-course AZT used in the United States and a short course of AZT given to the mother during the last month of pregnancy - a regimen tested in Thailand by the Centers for Disease Control and Prevention and reported effective in 1998.
Drugs costs alone are not the only barrier to HIV prevention. Access to other health care services required to implement this regimen, such as counseling and voluntary HIV testing, are beyond the resources of many developing countries. But if further research upholds nevirapine's good safety record, the investigators said that potentially all pregnant women who live in high prevalence areas could receive the drug during labor, even in the absence of an established HIV diagnosis.
Nevirapine, developed by Boehringer Ingelheim Pharmaceuticals, is a non-nucleoside reverse transcriptase inhibitor. Although it is in a different class of antiviral drugs than AZT, nevirapine works against the same HIV target enzyme that is critical for the virus to infect new cells.
Nevirapine is rapidly absorbed and transferred across the placenta to the infant, and it breaks down slowly.
If implemented widely, this new regimen could prevent HIV transmission to about 300,000 to 400,000 newborns, according to a press statement from the National Institute of Allergy and Infectious Diseases.
Long-term follow-up of both mothers and infants is needed to assess any late drug toxicities and long-term survival. They will continue to be actively followed until the infants are 18 months old. This period is critical to establish the efficacy of the intervention, researchers said.
Even if an infant is born free of HIV, he or she may acquire the virus during breastfeeding, which is practiced widely in developing countries. Most studies indicate that the rate of HIV transmission through breastfeeding is highest in the first few months of life. No intervention has yet been shown to prevent HIV transmission through breast milk other than not breastfeeding. The data analyzed so far cover only the first three months of the newborn's life. Investigators plan a follow-up study to evaluate the efficacy of nevirapine administered to the mother during labor and to the newborns for a longer period.
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