By JOHN SOLOMON, Associated Press Writer

WASHINGTON - U.S. health officials told Uganda's government that a U.S.-funded study there on using an AIDS drug to protect babies violated federal safety rules even though they didn't tell President Bush before he authorized shipping the drug to Africa.

The Department of Health and Human Services' Office for Human Research Protections identified nearly nine-pages of problems with the National Institutes of Health research project on nevirapine in Uganda in a July 2002 letter that pointedly identified several violations of federal patient protection rules.

The letter also proposed numerous corrective actions.

"OHRP find that the ARC (the project's oversight committee) failed to conduct continuing reviews of the above-referenced research as required by HHS regulations," the letter to Uganda's National Council of Science and Technology said.

The letter identified problems that included lowering, without permission, the standards for disclosing bad reactions during the drug research, and giving patients information about the risks "that may not have been understandable."

It was sent just a month after Bush, unaware of NIH's safety concerns about the research, authorized a $500 million initiative to use nevirapine throughout Africa to protect babies from getting HIV from infected mothers.

The Ugandan government thanked the U.S agency for its findings, adding it was sometimes difficult to meet ethical standards in poor countries.

"These conditions tend to dictate the level of compliance with the required ethical issues of biomedical research," the Ugandans replied.

Wednesday December 15, 7:33 AM

AP: U.S. Officials Knew of AIDS Drug Risks

But the National Institutes of Health never told the White House about problems it found in 2002 with its research on the drug nevirapine before President Bush unveiled a $500 million plan to distribute the medicine across Africa, documents obtained by The Associated Press show.

Instead, officials inside the government's premier health research agency scrambled to keep its safety experts' concerns from scuttling the use of nevirapine in Africa as a cheap solution to stopping babies from getting AIDS from infected mothers, the memos show.

"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 C. Tramont, reported March 14, 2002, to his boss, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

Since then, hundreds of thousand of doses of the drug have been administered to African mothers and babies under the Bush plan.

Up to half those babies may have been stopped from getting AIDS, officials said. But now concerns are emerging about whether patients who received those single doses have developed resistance to further AIDS treatment.

The documents show Tramont and other NIH officials dismissed the problems with the nevirapine research in Uganda as overblown and were slow to report safety concerns to the Food and Drug Administration.

A professional auditor hired by NIH who first helped disclose the problems said in an interview that most of the problems were fixable but NIH officials were in a rush to declare that things were OK.

"It seemed to me we were drawing conclusions too quickly across the board, especially the implementation of nevirapine in South Africa," auditor Michael Hensley told AP.

Ultimately, NIH did stop the Uganda research for 15 months _ from the spring of 2002 to the summer of 2003 _ to review the science and take corrective actions.

NIH officials told AP they remain confident after re-reviewing the Uganda study and other research that nevirapine can be used safely in single doses by African mothers and children to prevent HIV transmission during birth.

But they acknowledged their Uganda research failed to meet required U.S. standards and have asked the National Academy of Sciences to investigate.

"I would say there are many lessons that we have learned from this review that will help us do our clinical research, both domestically and internationally, much better," said Dr. H. Clifford Lane, NIH's No. 2 infectious disease official.

The White House said it remains confident in Bush's $500 million plan in 2002 to send nevirapine to Africa, a continent that accounts for more than two-thirds of the world's AIDS cases, with 27 million people infected. The United States approved $2.9 billion to fight global AIDS in 2005.

"We want to make sure that people in need are getting the help they need," Press Secretary Scott McClellan said Tuesday. "The president is firmly committed to combatting the AIDS pandemic, particularly in the most afflicted areas of the world and that's why we're moving forward on the president's emergency relief plan."

Though the White House was never told of the problems, they were serious enough that the U.S. Health and Human Services Department sent a nine-page letter to Ugandan officials identifying violations of federal patient protection rules by NIH's research.

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, a month after Bush's announcement of the nevirapine announcement.

NIH officials said a recent closer review of the Uganda research has identified a new concern _ that even single doses of nevirapine can create instant resistance. That means patients may not be able to use the drug or others in its class again when their AIDS worsens, Lane said.

"It was unexpected, and what it means is nevirapine probably shouldn't be a drug of first choice if other options are available," Lane said.

Lane said NIH officials were aware in spring 2002 of the impending White House announcement on nevirapine but did not tell presidential aides of the problems because they were confident, even before reviewing the Uganda research, that the underlying science was solid.

In order to reconstruct the research to make sure the science held up, NIH officials in summer 2002 found they couldn't use patient records because of sloppy record keeping and missing files. Instead, they had to review blood samples to determine which patients got the medicines.

Nevirapine is an antiretroviral drug marketed in the United States as Viramune. It has been used since the 1990s to treat adult AIDS patients and is known to have potentially lethal side effects like liver damage and 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 HIV transmission. 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 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 underreporting 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. found in March 2002. Westat is a medical auditing firm hired by NIH to visit and audit the Uganda site.

Westat reported 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.

NIH said the subsequent review whittled that list down significantly, all deaths were eventually recorded and the majority of bad reactions are believed to have been caused by the poor health of patients, not the single dose of nevirapine. But they conceded it was incumbent on a U.S. research project to disclose them fully and quickly.

Officials said the problems began when NIH converted the research from determining the drug's usefulness to supporting FDA approval for the drug. Paperwork in Uganda wasn't kept to FDA standards, they said.

"We may not have reported exhaustively, but we reported all serious side effects," said Professor Francis Mmiro, a lead doctor in the Uganda study. "What you may call a serious side effect in the U.S. is not a serious side effect in Kampala."

NIH officials reviewed the bad news in early March 2002.

Meeting minutes, written in shorthand, raised broad concerns: Half the babies in the study were also enrolled in a vitamin A study that could have affected the outcome, and medical staff running the trials didn't follow procedures for divulging serious adverse events (SAEs).

"No mtg minutes, no training doc(umentation), site used their own criteria for grading SAEs. No lab normal values & serious underreporting of SAEs," the minutes stated.

They also quote an NIH official who visited Uganda as saying, "The site staff doesn't know what they don't know."

But Tramont, the AIDS research chief, and other top NIH officials repeatedly dismissed the concerns as preliminary or overblown, and sought to salvage the flawed research's underlying conclusions rather than start over.

"There is presently no evidence that the study's scientific results are invalid," said a report Tramont sent to his staff less than two weeks after getting the March 2002 Westat audit.

In January 2002, Boehringer had sent NIH an early copy of its report. But the drug maker, fearing publicity about the report might destroy its chance to get FDA approval of the drug for domestic use, asked NIH to destroy it before FDA regulators could learn about it.

"Sensitive information. Asked for it to be destroyed when audit is upon us," NIH official Mary Anne Luzar wrote on the cover page of Boehringer's report.

But Boehringer says it never requested the document be destroyed, saying "our actions throughout the study evaluation were proactive and forthcoming."

Lane said the request to destroy the report was inappropriate and NIH never complied. But he conceded his agency inappropriately kept the audit from FDA for weeks, saying, "It shouldn't have happened that way."

NIH at first sought to postpone the FDA review of nevirapine, then top NIH and FDA officials arranged for the drug maker to pull its U.S. application rather than risk a public rejection that might scare African countries looking for U.S. guidance on the drug.

Unaware of the internal NIH concerns, Bush announced in June 2002 the $500 million effort to fight the spread of AIDS in Africa and the Caribbean. The plan's centerpiece was nevirapine.

"This major commitment of my government to prevent mother-to-child HIV transmission is the first of this scale by any government, anywhere," Bush said in a Rose Garden announcement.

African health officials are having second thoughts. South African officials in July recommended ending the single-use treatment because of the new concerns about drug resistance.

African doctors said they weren't aware of the full extent of NIH's concerns but feel comfortable _ at least until better options emerge _ administering it in single doses to AIDS-sickened mothers who have few other choices to protect newborns.

"It's not ideal, but it works," said Dr. Ashraf Coovadia of Coronation Mother and Child Hospital in Johannesburg, South Africa. Without it, "many, many more babies would be born with HIV."

Boehringer Ingelheim said it has donated enough doses to treat more than 411,000 mothers and infants in Africa, and self disclosed the problems it found with the Uganda research. But it says it has research from other locations, like Thailand and South Africa, showing single dose usage at birth is safe and effective.

"The bottom line is there were these procedural issues, such as the speed of reporting adverse events, and the like. But the important scientific data was intact, and found to be valid," said Dr. Patrick Robinson, a top Boehringer AIDS specialist.

Still, the German-owned company is no longer seeking FDA permission in 2004 to use nevirapine for protecting U.S. infants because better treatments have emerged, he said.

By The Associated Press

THE DRUG: Nevirapine, an AIDS drug pronounced Nee-VERA-peen, is made by Boehringer Ingelheim Corp. and is marketed under the brand name Viramune. There are two generic versions, Nevimune, made by Cipla, and Nevirex, made by Aurobindo Pharma.

HOW IT WORKS: Nevirapine, a non-nucleoside reverse transcriptase inhibitor, blocks an HIV protein that the virus uses to make new viral particles.

HOW IT IS USED: Nevirapine is generally taken once or twice a day in combination with other anti-AIDS drugs, such as AZT or didanosine.

EXPERIMENTAL USE: Nevirapine was tested in Uganda, Kenya and Thailand to see if a single dose to a mother in labor and one later to the newborn could prevent HIV transmission from an infected, pregnant woman to her baby.

RESISTANCE PROBLEMS: Studies found that birthing mothers who received nevirapine could develop an HIV virus resistant to some HIV drugs, including nevirapine. This could make their later AIDS treatment less effective.

SIDE EFFECTS: Liver toxicity occurs in some patients. About 16 percent of patients develop a skin rash. Other common side effects include nausea, fatigue, headache, vomiting, diarrhea and abdominal and muscle pain.

AP: Woman Died During Gov't AIDS Study

Family members of Joyce Ann Hafford say the 33-year-old HIV-positive woman died without ever holding her newborn boy. They also said they never were told the National Institutes of Health concluded the drug therapy likely caused her death.

The family first learned of NIH's conclusions when The Associated Press obtained copies of the case file this month. For the past year, they say they were left to believe Hafford, of Memphis, Tenn., died from AIDS complications but began pursuing litigation to learn more.

"They tried to make it sound like she was just sick. They never connected it to the drug," said Rubbie King, Hafford's sister.

"If it were the disease, solely the disease, and the complications associated with the disease, that would be more readily acceptable than her being administered medication that came with warnings that the medical community failed to get ... to her."

Documents show Hafford's case reverberated among the government's top scientists in Washington, who were monitoring reports of her declining health in late July 2003 as she lay on a respirator.

NIH officials quickly suspected the drug regimen because it included nevirapine, a drug known to cause liver problems, and the case eventually reached the nation's chief AIDS researcher.

"Ouch! Not much wwe (we) can do about dumd (dumb) docs," Dr. Edmund Tramont, NIH's AIDS Division chief, responded in an e-mail after his staff reported that doctors continued to administer the drugs nevirapine and Combivir to Hafford despite signs of liver failure.

Nevirapine is an antiretroviral AIDS drug used since the mid-1990s, and the government has warned since at least 2000 that it could cause lethal liver problems or rashes when taken in multiple doses over time.

Asked about the case Thursday, White House press secretary Scott McClellan called Hafford's death "tragic and terrible." He gave no view on whether use of multiple doses of the drug should be halted.

"We want to see what the National Institute of Medicine says," said McClellan. But he reiterated that the single dose of nevirapine used in the president's emergency AIDS relief plan in Africa is considered safe.

NIH officials acknowledge that experimental drugs, most likely nevirapine, caused Hafford's death, and that keeping the family in the dark was inappropriate. But NIH usually leaves disclosures like that to the doctors who treated her, officials said.

"We feel horrible that something like this would happen to anyone in any circumstance," said Dr. H. Clifford Lane, NIH's No. 2 infectious disease specialist. "There are risks in research and we try to minimize them."

Jim Kyle, a lawyer representing Regional Medical Center in Memphis where Hafford died, declined comment because of the family's pending litigation. The doctors there referred a call seeking comment to NIH.

The study during which Hafford died recently led researchers to conclude that nevirapine poses risks when taken over time by certain pregnant women.

"Continuous nevirapine may be associated with increased toxicity among HIV-1 infected pregnant women" with certain liver cell counts, the study concluded.

Lane said Hafford should have signed a 15-page, NIH-approved consent form at the start of the experiment specifically warning her of the risks of liver failure. The family says Hafford seemed unaware of the liver risks. They even kept the bottle of nevirapine showing it had no safety warnings.

"My daughter didn't know any of the warning signs," said Rubbie Malone, Hafford's mother and now caretaker of Hafford's new baby and older son. "She never got to hold her baby."

Lane confirmed the nevirapine bottle Hafford received likely wouldn't have had safety warnings because the experiment's rules called for the patient to be unaware of the exact drug effects to avoid patient influence on the test results. That means the consent form would have been her lone warning about potential liver problems, he said.

That 15-page, single-spaced consent form is chock full of complex medical terms like "hypersensitivity reactions" and "pharmacokinetic test." The warning about potential liver problems shows up on the sixth page, where it said liver inflammation was possible and "rarely may lead to severe and life threatening liver damage and death."

Hafford, who was HIV-positive but otherwise healthy, agreed to participate in the NIH-funded research project that provided her multiple doses of nevirapine, also known as Viramune, to protect her soon-to-be-born son, Sterling, from getting HIV at birth.

The project was an outgrowth of earlier research in Africa that concluded the drug could be taken in single doses safely to protect newborns half the time.

"She didn't want her baby to be born with HIV infection if it could be prevented at any cost," said King, her sister.

Hafford died Aug. 1, 2003, less than 72 hours after giving birth. Sterling was delivered prematurely by Caesarean section as his mother was dying. Though premature, he was spared from HIV and is healthy.

NIH's documents suggest Hafford's life might also have been spared if the drug had been stopped when the first liver problems showed up in her blood work two weeks before death.

"This case was particularly unfortunate b/c (because) the PI (principle investigative doctor) didn't stop drug when grade 3 liver enzymes were reported," Dr. Jonathan Fishbein, NIH's chief of good research practices, told Tramont in an August 2003 e-mail.

Fishbein, who is seeking federal whistleblower protection after raising concerns about NIH's practices, told AP that Hafford's death is attributable to a bigger problem in government research.

"This is not just a clinical trial issue this is a healthcare issue. The public expects that diagnostic test results are promptly evaluated and acted on, if need be," Fishbein said. "Sadly, this is but one example where an assessment was not done quickly and it cost this young mother her life."

NIH's official review determined the Memphis hospital failed to react to lab results that showed her liver failure was starting well before she died. "The site had identified that there was a delay in reviewing laboratory evaluations from the clinic visit the week before she presented with clinical hepatitis," an Aug. 15, 2003, report concluded.

The official investigative files cited "drug-induced hepatitis" of the liver as the cause of death.

As is routine after a research-related death, NIH ordered changes to the rules its researchers followed in the nevirapine studies to ensure the early detection of liver problems, the memos show.

By ALEXANDRA ZAVIS, Associated Press Writer

JOHANNESBURG, South Africa - Charmaine and her husband tried for over a year to have a child. The day she found out she was pregnant, a doctor told her she was HIV-positive.

Devastated, Charmaine considered abortion, but opted instead to try an AIDS drug called nevirapine to protect her newborn girl — now a healthy 1-year-old "miracle," she says.

Researchers now warn that taking a single dose of nevirapine during pregnancy can make mothers resistant to later treatment with the drug. The finding is threatening a program that's saved thousands of infants here from HIV transmission in the world's most HIV infected country, where 600 people die each day from AIDS-related complications.

In July, South Africa's Medicines Control Council recommended hospitals give up the single-dose nevirapine regimen in light of resistance concerns, saying mothers should take more effective — and expensive — "cocktails" of anti-retroviral drugs available in the United States and other wealthy countries.

But that would put protection out of reach for mothers like Charmaine, who gave only one name because of the stigma still associated with AIDS. South African doctors say until better options become available here they'll continue giving nevirapine to AIDS-sickened mothers.

"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," said Dr. Ashraf Coovadia, head of the pediatric HIV clinic at Johannesburg's Coronation Mother and Child Hospital. "If we just pull the plug on nevirapine ... many, many more babies would die."

South African regulators started asking questions about nevirapine when manufacturer Boehringer-Ingelheim withdrew its 2002 application with the U.S. Food and Drug Administration to market the drug in America to protect babies during birth.

The company noted serious irregularities in a key study conducted in Uganda. Top U.S. officials were warned of the problems weeks before President Bush announced a $500 million initiative in June 2002 to spread nevirapine in Africa, The Associated Press revealed this week.

Subsequent studies, however, confirmed the safety and efficacy of nevirapine, including one at Coronation hospital that found a single dose cut HIV transmission to 8.9 percent.

Nevirapine can cause severe rashes, liver toxicity and even death in some patients who use the drug on a daily basis to treat HIV, the virus that causes AIDS. But no serious reactions have been reported after a single dose, researchers say.

The main concern is that taking nevirapine during pregnancy can cause resistance to the drug, compromising the mother's future treatment. One study conducted here found that 39 percent of HIV-infected women who get a single dose go on to harbor virus that is resistant to the drug.

World Health Organization officials have been aware of the risk since 2000, but said that until recently few infected African mothers could afford life-prolonging anti-retrovirals. WHO says concerns about resistance must be balanced against the practicality of delivering a single dose of nevirapine and recommends it remain an option in impoverished African countries.

More than 5 million of South Africa's 45 million people are infected with HIV, more than any other country. Of the 1 million women who give birth every year, close to 28 percent are HIV-positive, and more than a quarter pass on the virus to their children, researchers say.

Studies have shown that a single dose of nevirapine to an infected woman during labor and another dose to her newborn baby can reduce the chances of HIV transmission by up to 50 percent.

Nevirapine taken with other drugs — as recommended by the South African regulatory body — and other combinations have cut transmission to less than 1 percent in the United States, Europe and Thailand.

But in South Africa, prenatal care is not widely available, and many pregnant women turn up at the hospital for the first time in labor — too late to start more complicated regimens.

The South African Health Department is reviewing its guidelines on mother-to-child transmission. But it says it will continue to provide single-dose nevirapine until an alternative is decided.

Doctors agree state hospitals should expand to more potent regimens, but not at the expense of hard-won programs.

President Thabo Mbeki's government long refused to provide anti-retrovirals through the public health system, citing cost and safety concerns.

In August 2001, a coalition of health workers and AIDS activists won a Constitutional Court ruling ordering the government to provide nevirapine to all HIV-infected pregnant women. But it wasn't until the government launched a comprehensive AIDS treatment program last April that the drug became widely available.

The South African government has promised to provide free treatment to all who need it within five years. Meantime, Boehringer-Ingelheim provides nevirapine free to protect newborns in many developing countries and, under international pressure, other drug manufacturers have slashed their prices in poor countries as well.

Activists from the Treatment Action Campaign say the nevirapine program remains patchy in South Africa, but thousands of HIV infections are being prevented at more than 1,500 sites where the drug is administered.

Charmaine was lucky. The hospital she delivered in had raised its own funds for nevirapine.

The woman lying next to her in the ward never got the drug. Her baby was born HIV-positive and died within two weeks. The mother also died of AIDS-related complications.

Despite the risks to her own treatment, Charmaine didn't hesitate to take nevirapine. Her doctor says it's too early to tell if she's become resistant to the drug.

"If it can help my baby, it is worth taking the risks," Charmaine said as her little girl played with a stethoscope on a recent medical visit. "She is the best thing that ever happened to me."

Docs Worry AIDS Drug Use May Be Halted

Doctors and AIDS activists in Africa are worried governments may halt use of an AIDS drug that has protected thousands of babies from HIV infection in reaction to new concerns about the drug's testing and effect on pregnant women.

The Rev. Jesse Jackson is calling for a U.S. congressional investigation into a report that U.S. health officials were warned that research on nevirapine was flawed. The warning was withheld from the White House weeks before President Bush announced a plan in 2002 to distribute the drug in Africa, The Associated Press reported this week.

The AP report said that testing of nevirapine at Uganda's Mulago Hospital failed to meet international standards and that pregnant women who take the drug once to inhibit passing HIV to their babies may develop resistance to it that can limit drug therapies to combat the deadly disease.

In calling for the investigation, Jackson demanded that nevirapine no longer be distributed in Africa.

"This was not a thoughtful and reasonable decision, but a crime against humanity," he said Thursday in Chicago. "Research standards and drug quality that are unacceptable in the U.S. and other Western countries must never be pushed onto Africa."

Dr. Saul Onyango, a medical officer involved in the testing, said African officials fear being denied use of the drug.

"It's an issue affecting people's lives. A lot of damage has already been done and we need to do damage control," Onyango said.

Dr. Francis Miiro, a key researcher, dismissed concerns about the testing as discrimination against African scientists and insisted the drug works safely.

In South Africa, the Treatment Action Campaign, which lobbied for access to anti-retroviral drugs in that country, warned that reopening debate about the Uganda study could frighten patients off their treatment, even though subsequent research has confirmed nevirapine is safe and effective.

"I don't see a problem with nevirapine at all," said the group's leader, Zackie Achmat, who found out he was HIV-positive in 1990. "I use it twice daily."

Doctors working in the public health system, which serves the vast majority of South Africans, have privately expressed fears they will be pressured to stop using single-dose nevirapine for pregnant women before alternatives are available.

"I'm of the view that we should use nevirapine till a better situation can be created," said Dr. Ashraf Coovadia, head of the pediatric HIV clinic at Johannesburg's Coronation Mother and Child Hospital. "To halt the program would cause damage to what we have already achieved."

Comment on radio talks shows in South Africa following publication of the AP stories in the local press have included worries that authorities will pull the drug.

President Thabo Mbeki's government has been criticized for its sluggish response to the AIDS crisis. Until this year, it refused to provide anti-retrovirals through the public health system, citing safety and cost concerns.

In July, a South African regulator recommended a halt to the single-dose nevirapine regime for pregnant women, saying a "cocktail" of drugs should be used instead even though such drugs are expensive and available mostly in the United States and other wealthy nations.

On Wednesday, the Health Department said U.S. concerns about the quality of nevirapine research in Uganda supported its cautious attitude to the drug and it was reviewing its guidelines on mother-to-child HIV transmission.

A spokesman, Sibani Mngadi, said the drug is still distributed by hospitals for now.

"It is part of a public health program which cannot be stopped just because this research is continuing," Mngadi said.

Studies show that a single dose of nevirapine to an infected woman during labor and another dose to her newborn baby can reduce the chances of HIV transmission by up to 50 percent.

Nevirapine can cause rashes, liver toxicity and even death in some patients who use the drug on a daily basis to treat HIV, but no serious reactions have been reported after a single dose.

But a South African study found that 39 percent of HIV-infected women who get a single dose of nevirapine go on to harbor virus that is resistant to the drug.

In Uganda, the official in charge of community health services said the issue had become a political one in the country, often praised for its efforts to stop the spread of AIDS.

"The issue is highly contentious, that's why some people don't want to be quoted," Dr. Sam Okware said. "It's been going on for two and a half years."

In a letter obtained by AP, U.S. health officials told Uganda's government in July 2002 that the research had violated federal patient safety rules. The memos show U.S. officials knew about the problems as early as January 2002, but chose not to tell President Bush before he authorized shipping the drug to Africa later as part of a $500 million initiative.

By ALEXANDRA ZAVIS, Associated Press Writer

JOHANNESBURG, South Africa - President Thabo Mbeki's ruling party published a stinging 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 fears 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 Associated Press reports this week that U.S. health officials withheld criticism of a nevirapine study before President Bush launched a 2002 plan to distribute the drug in Africa.

Documents obtained by AP show Dr. Edmund C. Tramont, chief of the National Institutes of Health's AIDS division, rewrote an NIH 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 record-keeping 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 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 of those lies on the lives of millions of Africans."

Smuts Ngonyama, an African National Congress spokesman and editor of the journal, said the article was an opinion piece by a member and didn't reflect official party policy. He wouldn't identify the author.

In the United States, the Rev. Jesse Jackson called for a U.S. congressional investigation and demanded nevirapine no longer be distributed in Africa.

"This was not a thoughtful and reasonable decision, but a crime against humanity," Jackson said Thursday in Chicago. "Research standards and drug quality that are unacceptable in the U.S. and other Western countries must never be pushed onto Africa."

Dr. H. Clifford Lane, the NIH's No. 2 infectious disease specialist and one of Tramont's bosses, has said an internal review cleared Tramont of scientific misconduct.

He said Tramont changed the report because he was more experienced than his safety experts and had an "honest difference of opinion." Tramont has also argued that Africans in the midst of an AIDS crisis deserved some leniency in meeting tough U.S. safety standards.

Activists in South Africa accused the Health Department and ruling party officials of putting out misleading statements that could frighten patients off their treatment, and worried that governments may now halt use of single-dose nevirapine before alternatives are available.

"NIH may be guilty of a cover up of bad (research) protocols, in which case we would be the first to want them held accountable," said Zackie Achmat, head of the Treatment Action Campaign. "But there is no doubt in my mind about the safety of nevirapine."

Some 70 percent of the 45 million people worldwide infected 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 pregnant women who receive a single dose can develop resistance to the drug that can compromise their future AIDS treatment.

A study in Uganda found that 20 percent of pregnant women and 46 percent of their babies developed resistance to nevirapine after taking one dose, a health official said. Scientists don't know the possible long-term effects on the women, said Dr. Philippa Musoke.

"Resistance does occur, but it fades after one year," Musoke said, adding that Uganda will continue distributing the drug "for the time being until we get an alternative."

WHO recommends nevirapine be used in combination with other drugs where possible — a strategy that has reduced transmission to less than 1 percent in wealthier countries. But it says resistance concerns must be weighed against the practicality of administering a single dose of nevirapine in impoverished African countries.

In July, South Africa's Medicines Control Council recommended that nevirapine only be used in combination with other drugs because of the resistance concerns.

The Health Department this week welcomed U.S. concerns about the quality of nevirapine research in Uganda, saying it supported its cautious attitude to the drug.

Until this year, Mbeki's government refused to provide anti-retroviral drugs through the public health system, citing safety and cost concerns. A coalition of doctors and AIDS activists won a 2002 Constitutional Court order requiring the government to immediately expand a pilot nevirapine program to all infected pregnant women.

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