14 December 2004
Washington -- Weeks before President Bush announced a plan to protect African babies from AIDS, top U.S. health officials were warned that research on the key drug was flawed and might have under-reported severe reactions including deaths, government documents show.
The 2002 warnings about the drug, nevirapine, were serious enough to suspend testing for more than a year, let Uganda's government know of the dangers and prompt the drug's maker to pull its request for permission to use the medicine to protect newborns in the United States.
But the National Institutes of Health, the government's premier health research agency, chose not to inform the White House as it scrambled to keep its experts' concerns from scuttling the use of nevirapine in Africa as a cheap solution, according to documents obtained by the Associated Press.
"Everyone recognized the enormity that this decision could have on the worldwide use of nevirapine to interrupt mother-baby transmission," NIH's AIDS research chief, Dr. Edmund Tramont, reported March 14, 2002, to his boss, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
The documents show Tramont and other NIH officials discussed the problems with the nevirapine research in Uganda as overblown and were slow to report safety concerns to the Food and Drug Administration.
NIH's nevirapine research in Uganda was so riddled with sloppy record keeping that NIH investigators couldn't be sure from patient records which mothers got the drug. Instead, they had to use blood samples to confirm doses, the documents show.
Less than a month after Bush announced a $500 million plan to make nevirapine available across Africa to slow the AIDS epidemic, the Health and Human Services Department sent a nine-page letter to Ugandan officials identifying violations of federal patient protection rules by NIH's research. Africa accounts for more than two-thirds of the world's AIDS cases, with 27 million infected.
The NIH research "may have represented a failure to minimize risk to the subjects," the Office of Human Research Protections told Ugandan authorities in summer 2002.
Nevertheless, NIH officials told AP they remained confident after re-reviewing the Uganda study and other research that nevirapine could be used safely in single doses by African mothers and children to prevent HIV transmissions during birth. But they acknowledged their Uganda research failed to meet required U.S. standards.
As a result, NIH recently asked the National Academy of Sciences to investigate its science in the case, and it has spent millions in the last two years improving its safety monitoring and record keeping.
Senate Finance Committee Chairman Charles Grassley, R-Iowa, has asked the Justice Department to investigate NIH's conduct.
Dr. H. Clifford Lane, NIH's No. 2 official on infectious diseases, said NIH officials had been aware in spring 2002 about the impending White House announcement on nevirapine but had not told presidential aids of the problems because they were confident, even before reviewing the Uganda research, that the underlying science was solid.
The White House -- though unaware of the NIH concerns -- also remains confident in Bush's $500 million plan in 2002 to send nevirapine to Africa. Bush approved $2.9 billion for global AIDS fighting next year.
"The president's mission is to try to stop the spread of AIDS in Africa and to come at it from a new angle, and that is what this is all about," said spokesman Trent Duffy.
Nevirapine is an antiretroviral drug marketed in the United States as Viramune that has been used since the 1990s to treat adult AIDS patients and is known to have potentially lethal effects such as liver damage and to cause severe rashes when taken over time.
In 1997, NIH began studying in Uganda whether it could be given safely in single doses to stop mother-to-baby transmissions. That research showed it could reduce transmission in as many as half the births.
But by early 2002, an NIH auditor, the agency's medical safety experts and the drug's maker all disclosed widespread problems about the U.S.-funded research in Uganda.
Boehringer Ingelheim, the Connecticut-based company that makes nevirapine, told NIH it had identified at least one "critical compliance issue" that compromised the integrity of the study and more than four dozen issues it described as "serious" and "major."
Boehringer and NIH auditors cited concerns such as failing to get patients' consent about changes in the experiment, administering wrong doses and delays and under-reporting of "fatal and life-threatening" problems.
"It appeared likely, in fact, that many adverse events and perhaps a significant number of serious adverse events for both mother and infant may not have been collected or reported in a timely manner," Westat Corp. reported in March 2002. Westat is a professional medical auditing firm hired by NIH to visit and audit the Uganda site.
Westat reported that there were 14 deaths not reported in the study database as of early 2002 and that the top two researchers in Uganda acknowledged "thousands" of bad reactions that weren't disclosed.
Reprinted from The San Francisco Chronicle 14 December
16 December 2004
Johannesburg: President Thabo Mbeki's ruling party published an attack Friday on top U.S. health officials, accusing them of treating Africans like "guinea pigs" and lying to promote a key AIDS drug.
The criticism reinforces fear of doctors and activists that new questions about the testing of nevirapine could halt use of the drug that's credited with protecting thousands of African babies from catching HIV from their mothers.
The article, published in the online journal ANC Today, was responding to news reports this week that U.S. health officials withheld criticism of a nevirapine study before President Bush began a 2002 plan to distribute the drug in Africa.
Documents obtained by the Associated Press show that Dr. Edmund Tramont, chief of the National Institutes of Health's AIDS division, rewrote an Institute report to omit negative conclusions about the way a U.S.-funded drug trial was conducted in Uganda and later ordered the research to continue over the objections of his staff. Tramont's staff worried about recordkeeping problems, violations of federal patient safeguards and other issues at the Uganda research site.
"Dr. Tramont was happy that the peoples of Africa should be used as guinea pigs, given a drug he knew very well should not be prescribed," the ANC Today article said. "In other words, they entered into a conspiracy with a pharmaceutical company to tell lies to promote the sales of nevirapine in Africa, with absolutely no consideration of the health impact on those lives of millions of Africans."
About 70 percent of the 45 million people worldwide with HIV live in sub-Saharan Africa.
Studies have shown that a single dose of nevirapine to an infected woman during labor and another dose to her newborn can reduce the chances of HIV transmission by up to 50 percent. Nevirapine is also used in combination with other drugs to prolong the lives of AIDS patients.
Subsequent research has confirmed the safety and efficacy of
nevirapine in protecting newborns, the World Health Organization says.
But there's evidence that pregnant women who receive a single dose can
develop resistance to the drug that can compromise their future AIDS
Reprinted from the San Francisco Chronicle, 16 December 2004.