Articles on Nevirapine Trial Might Threaten Drug’s Use Among Newborns, South African AIDS Experts Say
A recent series of Associated Press articles "criticizing the conduct" of a trial of the antiretroviral drug nevirapine among pregnant women in Uganda is "threatening to undermine" the drug's use to prevent infection among newborn infants in developing countries, according to some South African HIV/AIDS experts, BMJ reports (Roehr, BMJ, 1/8). The articles concerned an NIH-funded trial that began in 1997 to study the use of nevirapine in single doses among HIV-positive pregnant women in Uganda to determine the drug's ability to prevent vertical HIV transmission. The initial results showed that the drug prevented HIV transmission to newborns in as many as half of births. By early 2002, medical safety specialists and auditors with NIH as well as the drug's manufacturer Boehringer Ingelheim all cited "widespread" problems with the research in Uganda -- including a failure to receive participants' consent about changes in the study, administration of incorrect doses, and delays in reporting and underreporting of fatal and life-threatening reactions to the drug. Because of the reported problems, NIH suspended the research from spring 2002 to summer 2003 in order to review the trial and take corrective steps. Last month, National Institute of Allergy and Infectious Diseases Division of AIDS Director Dr. Edmund Tramont also admitted to rewriting a safety report on the use of nevirapine in pregnant women in order to change its conclusions and remove negative information about the drug. However, NIAID in a recent Q & A document regarding the trial said that nevirapine is a "safe and effective" treatment to reduce the risk of vertical HIV transmission and that reviews of the study data "have found only a very small number of serious adverse reactions that potentially might be due to nevirapine" (Kaiser Daily HIV/AIDS Report, 1/5). NIH in July 2004 asked the Institute of Medicine to conduct a review of the Ugandan trial, and its results are expected in March.
Although "many" HIV/AIDS experts say that the Associated Press articles contained "little that was not already known" about the risks associated with nevirapine and presented some incorrect information and "distorted" facts, they have "provided ammunition" to some groups that have "long been opposed" to expanding antiretroviral treatment programs in developing countries, according to BMJ. Concerns over resistance developing from single-dose nevirapine in July 2004 led South Africa's Medicines Control Council to recommend using combination antiretroviral therapy to reduce the risk of vertical HIV transmission, according to BMJ. However, the cost of combination therapy "remains a prohibitive factor," BMJ reports (BMJ, 1/8). In addition, South Africa's ruling party, the African National Congress in an article published last month on its Web site accused the United States of treating Africans like "guinea pigs" and "entering into a conspiracy" with Boehringer to conceal potential adverse effects of nevirapine use. The article also implied that U.S. officials had covered up several nevirapine-related deaths (Kaiser Daily HIV/AIDS Report, 12/20/04). Other groups -- such as South Africa's Treatment Action Campaign -- have "rejected" ANC's statements, saying that there "is not a single reported life-threatening adverse event associated with this regimen, which is widely used in the developing world," BMJ reports. Dr. Ashraf Coovadia, head of the pediatric HIV clinic at Johannesburg's Coronation Mother and Child Hospital, told the Associated Press, "You can't apply a standard here in Africa that says until we can get the Rolls-Royce of treatment, let's not do anything," adding, "If we pull the plug on nevirapine, many, many more babies will die." UNAIDS estimates that 1,900 infants are born HIV-positive every day worldwide and that most of those infections could be prevented, according to BMJ (BMJ, 1/8).