No Evidence of Serious Flaws in NIH-Funded Study of Nevirapine Use Among Pregnant Women in Uganda, IOM Report Says

There is no evidence of serious flaws in an NIH-funded study of the antiretroviral drug nevirapine among pregnant women in Uganda that would "cast doubt" on the study's findings, according to a report released on Thursday by an independent review panel of the Institute of Medicine, the Baltimore Sun reports (Bor, Baltimore Sun, 4/8). The IOM panel investigated the trial -- called HIVNET 012 -- which began in 1997 to study the use of single-dose nevirapine among HIV-positive pregnant women in Uganda to prevent vertical HIV transmission. The initial results showed that the drug prevented HIV transmission to newborns in as many as half of births. However, by early 2002, medical safety specialists and auditors with NIH, as well as the drug's manufacturer Boehringer Ingelheim, cited administrative problems with the research in Uganda. Because of the reported problems, NIH suspended the research from spring 2002 to summer 2003 and in 2004 asked IOM to review the trial. 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" (Kaiser Daily HIV/AIDS Report, 3/16).

Panel Findings
Although the panel reported that there were "shortcomings" in the study, it said that the trial "generally adhered to research standards and provided strong evidence" that nevirapine reduces the risk of vertical HIV transmission, according to the Boston Globe (Smith, Boston Globe, 4/8). "The data from the HIVNET 012 study, which showed that nevirapine effectively prevents many infants from contracting HIV from their infected mothers, are sound and reliable," James Ware, a professor of biostatistics at the Harvard School of Public Health and chair of the IOM panel, said, adding, "None of the shortcomings that we discovered upon reviewing the data and conducting our own original analysis of source documents indicates a need to retract or discount the study's findings" (Fox, Reuters, 4/7). In addition, the committee found "no reason that medical journals should revise or retract articles that reported on the efficacy and safety of nevirapine" for reducing vertical HIV transmission, according to an IOM release (IOM release, 4/7). The panel found that the researchers failed to report some adverse health events in some infants included in the study but also found no evidence of underreporting of infant deaths or differing results about children taking nevirapine or zidovudine, the other antiretroviral drug included in the study, according to VOA News. Mark Kline, a pediatric AIDS specialist at Baylor College of Medicine and an IOM panel member, said, "Nevirapine really is the cornerstone of efforts to reduce mother-to-child transmission of HIV in poor countries around the world, particularly in Africa, so the concerns that have been raised about the study really have had a chilling effect on the use of this drug," adding, "So we're happy to report that the drug is efficacious and is safe because we would obviously like to do anything we possibly can do to help to provide tools for the prevention of mother-to-child transmission of HIV in poor settings around the world" (McAlary, VOA News, 4/7).

Reaction
The IOM report likely will not end congressional and federal investigations into whether NIH safety and legal guidelines were violated by front-line researchers and managers in this study and other studies, according to the AP/Long Island Newsday (Solomon, AP/Long Island Newsday, 4/7). However, NIH said it expects the IOM findings to "restore confidence in the validity of the conclusions of this study, allow the controversy surrounding this issue to subside and facilitate policy decisions that seek to promote the health of newborns at risk of HIV infection," according to an NIH release (NIH release, 4/7). Mark Isaac, vice president of the Elizabeth Glaser Pediatric AIDS Foundation, said, "The IOM's review is a true public service that allows us to settle any lingering concerns about the safety and efficacy of nevirapine," adding, "Now we can once and for all put this issue to rest and focus our time and energy on the real issue of saving the lives of women and children in the developing world" (EGPAF release, 4/7). However, Jonathan Fishbein, the former NIH employee who "first sounded an alarm" about the study and now is suing the agency over his subsequent firing for alleged poor performance, said he takes the IOM report "with a grain of salt." He added that the Uganda study "can't be considered as part of the useful body of knowledge about nevirapine. This study is garbage" (Boston Globe, 4/8).

NPR's "Morning Edition" on Friday reported on the panel's review. The segment includes comments from Kline and Isaac (Wilson, "Morning Edition," NPR, 4/8). The complete segment is available online in RealPlayer.