IOM To Publish Review of Trial Testing Nevirapine Use in HIV-Positive Pregnant Ugandan Women
An Institute of Medicine independent study expected to be published later this month aims to "settle serious questions" about apparent "flaws" with recordkeeping in an NIH-funded study on the use of the antiretroviral drug nevirapine among pregnant HIV-positive women in Uganda, Nature Medicine reports (Check, Nature Medicine, March 2005). A series of Associated Press articles published in December 2004 criticized the conduct of a trial that began in 1997 to determine whether and to what extent single-dose nevirapine prevents vertical HIV transmission. The initial results showed that the drug prevented vertical transmission in as many as half of births, but by early 2002, medical safety specialists and auditors with NIH as well as Boehringer Ingelheim, which produces nevirapine under the brand name Viramune, cited administrative problems with the research. 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. In response, the National Institute of Allergy and Infectious Diseases in a 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." NIH in July 2004 asked IOM to conduct a review of the Ugandan trial (Kaiser Daily HIV/AIDS Report, 1/20).
HIV/AIDS Advocates Reaction, NIH Policy Changes
HIV/AIDS advocates say that the IOM report is "unlikely" to resolve the "most important lesson" from the trial, which is that poor countries cannot be expected to conduct research that meets U.S. standards without "comparable funding," Nature Medicine reports. Ugandan researchers did not receive money for the study from NIH to offset overhead costs, such as the cost of buildings, instruments and computers, according to Arthur Ammann, president of the not-for-profit advocacy group Global Strategies for HIV Prevention, Nature Medicine reports. Currently, NIH allows foreign grantees to apply for additional funding for overhead costs up to 8% of the total grant amount but allows U.S. institutions to apply for up to 30% in additional funding for overhead costs. But critics say there should be "complete parity" between grants to U.S. and foreign institutions, according to Nature Medicine (Nature Medicine, March 2005).
The Associated Press articles have been "widely misconstrued to the potential detriment of public health" and might "lead to the decreased use in developing countries of a proven intervention" to block vertical HIV transmission when "no other options are available," NIAID acting Deputy Director Clifford Lane, NIAID Special Assistant for Research Reporting Gregory Folkers and NIAID Director Anthony Fauci write in a Nature Medicine opinion piece. "[M]ultiple" U.S. and international reviews of nevirapine have "consistently supported" the safety and efficacy of the drug, they say. In addition, Fauci, Lane and Folkers say that NIAID Division of AIDS Director Dr. Edmund Tramont did not "alte[r]" the results of the Ugandan study, although the Associated Press reported that Tramont 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. "In settings where other options are not available," nevirapine "remains a recommended and valuable public health tool," the authors conclude (Lane et al., Nature Medicine, March 2005).
NPR's "All Things Considered" on Sunday reported on the use of nevirapine. The segment includes comments from Dr. Francois Dabis of Bordeaux University; Mark Isaac, vice president for policy and communications for the Elizabeth Glaser Pediatric AIDS Foundation; Dr. Richard Marlink, executive director of the Harvard AIDS Initiative at the Harvard School of Public Health; and Dr. Moses Sinkala, director of the Zambian Ministry of Health (Knox, "All Things Considered," NPR, 3/6). The complete segment is available online in RealPlayer.
NPR's "All Things Considered" also reported on physicians and HIV/AIDS advocates who say politicians in South Africa are "misguided" in their contention that nevirapine "might be unsafe." The segment includes comments from Mark Heywood of the South African HIV/AIDS advocacy group Treatment Action Campaign and Dr. James McIntyre, director of perinatal research at the Chris Hani Baragwanath Hospital in Johannesberg (Wilson, "All Things Considered," NPR, 3/6). The complete segment is available online in RealPlayer.