{"article":{"id":120358,"heading":"The NIH Two-Step - Stepping Over Bodies on the Way to Market","author":"Liam Scheff","created":"2004-12-19 21:16:00","modified":"2013-11-11 00:31:48","last_modified":"Mon, 11 Nov 2013 07:31:48","article":"

This week, Dr. Edmund Tramont, Head of the National Institutes of Health (NIH) AIDS division, was outed by fellow NIH AIDS researcher Dr. Jonathan Fishbein, for burying evidence of drug toxicity in an African drug trial. Tramont censored reporting of thousands of toxic reactions and at least 14 deaths in the ongoing Nevirapine study in Uganda.

The media has seized on this like it’s news, but the truth about Nevirapine was known in 2000, when the FDA put a black-box label on the drug, warning of the drug’s ability to cause fatal liver damage and bloody rupturing of skin and flesh.

The drug’s manufacturer, Boehringer Ingelheim, wanted to get the drug into the US market for use in pregnant HIV-positive women. But the drug’s toxicities were so great, they pulled it out of the FDA approval process. Then they did what all drug companies do with their garbage – dump it into impoverished foreign markets and tell the soft-headed liberal media that it’s an AIDS drug.

The Ugandan study that Tramont helped bury was overseen by Dr. Laura Guay, a US doctor from Johns Hopkins University School of Medicine. Under Dr. Guay, the drug found its approval overseas. How does a drug that kills Americans save Africans?

South African lawyer and journalist Anthony Brink scrutinized the study in \"The Trouble With Nevirapine\" first published in April 2002, and updated this year. Dr. Fishbein tracked down Brink, whose study he described as \"an expertly written piece about this very dangerous drug.\"

There’s not a word in the current NIH mea culpa that Brink didn’t outline in greater detail a year and a half ago.

The Ugandan study started like all AIDS drug trials do. Dr.Guay discarded the study controls. There was no placebo group to compare the Nevirapine group to. Everybody was on one of two cell-killing drugs – Nevirapine or AZT.

The study put pregnant women on one of the two pills at labor. Why at labor? The idea is to prevent transmission of HIV from mother to child. The mother’s HIV status is determined, of course, by what we call an HIV antibody test.

Here’s a clever bit of information left out of the NIH report and the mainstream press coverage - HIV test inserts warn that pregnancy produces antibodies which cause the tests to come up positive. Pregnancy, on its own, creates positive HIV test results. You’ll find this over and over again in the medical literature. But it was ignored in Uganda (as it is in the US, every day).

The other line of missing logic in the Ugandan study is that, according to the test manufacturers, no child can be tested for at least 18 months with any certainty, because of normal “passive transmission of maternal antibodies” that can trip up the hyper-reactive HIV tests.

So, what are we trying to prevent transmission of? Antibodies? Pregnancy? Who knows.

In order to get around the standard tests’ short-comings, the babies were instead tested with a genetic kit called PCR. But here’s the joke. PCR isn’t validated or approved to diagnose viral infection.

PCR is irreproducible. In the lab, it gives wildly varying results for the same sample. There’s no standard to measure it against.

PCR tests amplify scraps of unidentifiable genetic material in cells. Researchers like to pretend that this material represents some aspect of a virus – but the manufacturer warns specifically against using the test for this purpose:

“The AMPLICOR HIV-1 MONITOR Test….is not intended to be used as a screening test for HIV or as a diagnostic test to confirm the presence of HIV infection.” (Roche PCR HIV-1 Monitor Test)

But that’s exactly how doctors and researchers are using it, to get infants into a drug study.

Where’s the liberal media on this issue - Mother Jones, Democracy Now? I’ve presented it to DN, several times, and apparently, they can’t be bothered with it. After all, how could the medical establishment be wrong?

But even if the tests were accurate, and the drugs weren’t biological weapons, there’s a terrible flaw in these studies. To paraphrase Brink - what’s the purpose of a last-minute drugging to prevent the passage of a retrovirus, when the child and mother have been sharing the same blood, tissue, cells and body for nine months?

Adding insult to injury, the Guay study also became immediately unblinded. Everybody knew who was on Nevirapine, who was on AZT, and who tested positive. In the absence of a controlled, well-observed study, participants tend to give into panic, pill-sharing, over-consuming, and the mixing in of non-study drugs to try to get the HIV-antibody response to go away.

The results of Guay’s study came in with an official recommendation for Nevirapine, but only after recording a 20% rate of “serious adverse events” in both the Nevirapine and AZT groups. Patients on the drugs had blood and tissue infection, pneumonia, blood cell death, severe rash and insufficient oxygen reaching their tissues.

Thirty-eight babies died. Sixteen on Nevirapine, twenty-two on AZT.

The drug was approved because the rate of PCR-inferred viral infection in the Nevirapine infants was 13.1%. Lower than that of the AZT group’s PCR rating. What’s PCR? A non-diagnostic test with no standard that gives different results for every sample.

According to the medical\/pharmaceutical establishment, it was enough to get a profitable, deadly drug into the international marketplace. (Dead babies don’t mean much there).

If that doesn’t penetrate your skull, try this. A study was done in 1998 with 561 expectant African mothers to see what the rate of presumed HIV infection was with no drugs, no pills and no placebos. The result – 12%. Less than 13.1? Sure. But where’s the money in not drugging them?



This summer in America, the same drug was being used in an NIH sponsored trial of US patients. Another expectant mother, Joyce Ann Hafford, had been dosed with Nevirapine (commercially sold here as “Viramune”) because she too had a reaction on an HIV test.

Hafford was 33. Before entering the study, she was healthy and pregnant, but was convinced to go on the drug because of her HIV test result. In early August doctors knew that Hafford’s liver was failing. But they kept her on the drugs.

She died two weeks later due to “drug-induced hepatitis” – fatal liver poisoning. An emergency cesarean-section was performed to get her baby out of her dying body. Neither she nor her family had been given the drug’s boxed warning label prior to her entrance into the study. If she had, she might be here today.

The Nevirapine (Viramune) label:

“Warning: Severe, life-threatening, and in some cases fatal hepatotoxicity [liver poisoning], including fulminant and cholestatic hepatitis, hepatitic necrosis [liver death] and hepatatic [liver] failure, has been reported in patients treated with VIRAMUNE [Nevirapine]…Patients with signs or symptoms of hepatitis must discontinue VIRAMUNE and seek medical evaluation immediately.

Severe, life-threatening skin reactions, including fatal cases, have occurred in patients treated with VIRAMUNE. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis [skin death], and hypersensitivity reactions characterized by rash, constitutional findings and organ dysfunction.

It is essential that patients be monitored intensively during the first 18 weeks of therapy with VIRAMUNE to detect potentially life-threatening hepatotoxicity or skin reactions….In some cases, hepatatic injury has progressed despite continuation of treatment. VIRAMUNE should not be restarted following severe hepatatic, skin, or hypersensitivity reactions.”

Dr. Edmund Tramont, of the NIH, had these thoughtful words to offer on the subject.

\"Ouch! Not much wwe (we) can do about dumd (dumb) docs,\" he wrote, in an inner-office email, leaked to the Associated Press.

“Ouch! Not much we can do about dumb docs?”

Sure there is. We can take them to court. In droves.

But maybe it’s time that the rest of us got smart, and began to regard the NIH with the same unblinking critical eye that we do any other money-driven corporate entity. The day that the Left stops pretending that the NIH is going to solve the world’s health problems, we might actually start saving some lives.



For more on Nevirapine, see the 2001 European Study photos and link at \"Altheal.org\":http:\/\/www.altheal.org\/toxicity\/orphans.htm<\/a>

<\/p>\n","contact":"","link":"","address":"","phone":"","parent_id":0,"mime_type":"text\/plain","summary":"The major media is finally covering the toxicity of what pharmaceutical companies mislabel 'AIDS Drugs,' but they're four years and hundreds of deaths too late","numcomment":3,"fileurl":"\/uploads\/","filesize":null,"article_url":"\/news\/2004\/12\/120358.php"},"attachments":[],"comments":[{"id":120383,"heading":"Liam Scheff should learn some medicine","article":"Sadly Mr Scheff needs to learn some basic medicine, and read the HIVNET012 study protocol. \r\n\r\n1. The placenta is designed to prevent maternal and fetal blood from mixing. HIV only rarely infects DURING pregancy. C-section can prevent infection, since it mostly occurs as the baby travels down the birth canal. Treating at the time of birth therefore makes good sense. \r\n\r\n2. Pregnancy causes very rare false-positive reactions on the HIV tests. One recent study put it at 0.44% in a "high" rate group. Also the Ugandan study used full US-style testing with confirmatory Western Blot, not just rapid ELISA. \r\n\r\n3. The tests used for neonatal diagnosis are used routinely: not every RNA test is unapproved in diagnosis! One was approved in September 2001 by the FDA for the purpose of screening samples. Additionally the infections in infants were actually confirmed by additional RNA tests, virus cultures, and serology after the magical 18 month value Mr Scheff mentions. \r\n\r\n4. Nevirapine is still approved to treat HIV, despite what he says in the article. The toxicity problem is no different from, say, Tylenol which also causes fatal liver toxicity. The study problem he rightly enough draws attention to is not one of AIDS drugs, but one of study docs (in this single instance) not paying enough attention to their patients. \r\n\r\nThe study protocol is freely available online at \r\n http:\/\/www.hptn.org\/Web%20Documents\/HIVNET_Protocols\/HIVNET012v2.pdf \r\n\r\nThere really should be no excuse for mis-representing it. \r\n\r\nBennett ","author":"Bennett","parent_id":120358,"mime_type":"text\/plain","created":"2004-12-21 03:52:35","modified":"2004-12-21 03:52:35","fileurl":""},{"id":120562,"heading":"Utter nonsense by Bennett","article":"Serious Adverse Events Attributed to Nevirapine Regimens \r\nfor Postexposure Prophylaxis After HIV Exposures --- Worldwide, 1997--2000\r\n\t\r\n\r\nFROM THE CDC ITSELF\r\n\r\n\r\nIn September 2000, two instances of life-threatening hepatotoxicity were reported \r\nin health-care workers taking nevirapine (NVP) for postexposure prophylaxis (PEP) \r\nafter occupational human immunodeficiency virus (HIV) exposure*. In one case, a \r\n43-year-old female health-care worker required liver transplantation after developing \r\nfulminant hepatitis and end-stage hepatic failure while taking NVP, zidovudine, and lamivudine \r\nas PEP following a needlestick injury (1). In the second case, a 38-year-old male \r\nphysician was hospitalized with life-threatening fulminant hepatitis while taking NVP, \r\nzidovudine, and lamivudine as PEP following a mucous membrane exposure. To characterize \r\nNVP-associated PEP toxicity, CDC and the Food and Drug Administration (FDA) \r\nreviewed MedWatch reports of serious adverse events in persons taking NVP for PEP received \r\nby FDA (Figure 1). This report summarizes the results of that analysis and indicates \r\nthat healthy persons taking abbreviated 4-week NVP regimens for PEP are at risk for \r\nserious adverse events. Clinicians should use recommended PEP guidelines and dosing \r\ninstructions to reduce the risk for serious adverse events.\r\n\r\nMedWatch is a voluntary reporting system for adverse events and problems \r\nwith drugs, medical devices, biologics, and special nutritional products. For this analysis, \r\na serious adverse event was defined as any event that was life-threatening, \r\npermanently disabling, required or prolonged hospitalization, required intervention to prevent \r\npermanent impairment or damage, or any other event that required medical attention.\r\n\r\nIncluding the two case reports of fulminant hepatitis, FDA received reports of \r\n22 cases of serious adverse events related to NVP taken for PEP from March 1997 \r\nthrough September 2000. These 22 events included hepatotoxicity (12), skin reaction (14), \r\nand rhabdomyolysis (one); four cases involved both hepatotoxicity and skin reaction, \r\nand one case involved both rhabdomyolysis and skin reaction. The median age of \r\naffected persons was 36.5 years (range: 12--50 years; age was not reported for four cases); \r\n12 were female, and 12 occurred in the United States. Reasons for administration of \r\nPEP were occupational needlestick or other sharps injury (12), other occupational \r\nexposure (four), sexual exposure (three), nonoccupational (pediatric) needlestick injury (one), \r\nother nonoccupational exposure (one), and unknown (one).\r\n\r\nNine persons took a maximum NVP dose of 200 mg per day, and 12 persons took \r\na maximum dose of 200 mg twice per day (the dose of NVP was not recorded for \r\none person). Among the 12 persons taking a maximum dose of 200 mg twice daily, six \r\nwere first given a lead-in dose of 200 mg per day for 3--14 days. Concomitant \r\nantiretroviral agents used with NVP for PEP included zidovudine and lamivudine (10); stavudine \r\nand lamivudine (three); zidovudine and didanosine (two); stavudine and didanosine \r\n(one); stavudine and indinavir (one); didanosine and indinavir (one); stavudine, didanosine, \r\nand ritonavir (one); lamivudine, didanosine, and nelfinavir (one); stavudine, \r\nlamivudine, nelfinavir, and saquinavir (one); and none (one). Among the 12 persons with \r\nhepatotoxic reactions, one developed liver failure (requiring liver transplantation), seven had \r\nclinical hepatitis (e.g., jaundice, fever, nausea, vomiting, abdominal pain, and\/or \r\nhepatomegaly), and four had elevations in serum liver enzymes (i.e., alanine aminotransferase [ALT] \r\nand aspartate aminotransferase [AST]) without reports of clinical hepatitis. \r\n\r\nBaseline liver function tests were reported for six patients and were within \r\nnormal limits. Abnormal liver function tests were reported during PEP for 10 patients; \r\nmedian \r\npeak ALT was 215 U\/L (range: 182--2790 U\/L; normal: 10--34 U\/L), median peak AST \r\nwas 375 U\/L (range: 96--2370 U\/L; normal: 10--34 U\/L), and median peak total bilirubin was \r\n7.5 mg\/dL (range: 2.0--33.7 mg\/dL; normal: 0.2--1.0 mg\/dL). The median time from \r\ninitiation of NVP use to first abnormal liver function tests was 21 days (range: 13--36 days). In \r\nsix cases, hepatitis A, B, and C serologies were reported; all were negative. Eleven \r\npersons reported symptoms, including fever, malaise, and abdominal pain. The median onset \r\nof these symptoms was 14 days after beginning NVP for PEP (range: 3--36 days). The \r\n14 reports of skin rash included one documented and two possible cases of \r\nStevens-Johnson syndrome. The median onset of rash occurred 9 days after beginning PEP (range: \r\n6--36 days).\r\n\r\nReported by: D Boxwell, Pharm D, Office of Postmarketing Drug Risk Assessment; H \r\nHaverkos, MD, S Kukich, MD, K Struble, Pharm D, H Jolson, MD, Div of Anti-Viral Drug Products, Center \r\nfor Drug Evaluation and Research, Food and Drug Administration. Prevention and Evaluation \r\nBr, Div of Healthcare Quality Promotion [proposed], National Center for Infectious Diseases, CDC.\r\n\r\nEditorial Note:\r\n\r\nSevere, life-threatening, and fatal cases of hepatotoxicity and \r\nskin reactions have occurred among HIV-infected patients treated with NVP \r\n(2,3) and are described in a box warning on the NVP label (Viramune\u2122 [package \r\ninsert]\u2020, Boehringer Ingelheim\/Roxane Laboratories, Inc., Ridgefield, Connecticut, 1998). This report \r\nsuggests that persons taking NVP regimens for PEP after HIV exposures also are at risk \r\nfor serious adverse events.\r\n\r\nIn 1996, the U.S. Public Health Service (PHS) first recommended PEP after \r\ncertain occupational exposures to HIV (4). These recommendations, updated in 1998 \r\n(5), are being revised to include other antiretroviral agents that have been approved by FDA \r\nfor use in HIV-infected persons. NVP is not recommended for basic or expanded PEP \r\nregimens. However, data on the safe and effective use of single-dose NVP to prevent \r\nperinatal HIV transmission (6,7) and a theoretical advantage of more rapid activity (i.e., \r\nNVP does not require phosphorylation for activation) have prompted clinicians to include \r\nNVP in PEP regimens following HIV exposures. In the HIV PEP registry, which collected data \r\non occupational HIV PEP use from October 1995 through March 1999, six cases of \r\nserious adverse events related to PEP were reported among 492 registered participants; a \r\nsevere skin reaction occurred in one of 11 health-care workers taking a regimen \r\nthat included NVP (8).\r\n\r\nBecause most occupational HIV exposures do not result in transmission of HIV \r\n(9), clinicians considering prescribing PEP for exposed persons must balance the risk for \r\nHIV transmission represented by the exposure and the exposure source against the \r\npotential toxicity of the specific agent(s) used \r\n(4). In many circumstances, the risks \r\nassociated with NVP as part of a PEP regimen outweigh the anticipated benefits. When PEP is \r\nprescribed, the manufacturer's package insert should be consulted for dosing \r\ninstructions, possible side effects, and potential drug interactions.\r\n\r\nThe findings in this report are subject to at least three limitations. First, MedWatch \r\nis a voluntary, passive reporting system, and it is unlikely that all serious adverse events \r\nin persons taking NVP for PEP have been reported. Second, data about administration of \r\na lead-in dose and results of baseline liver function tests and hepatitis serologies were \r\nnot included in all reports. In six cases, the initial dose of NVP was 200 mg twice daily \r\nwithout the recommended 2-week dose escalation, which may have increased the likelihood \r\nof adverse events (10). Third, available denominator data about the use of NVP for \r\nPEP were insufficient to calculate accurate rates of adverse events.\r\n\r\nThe findings in this report do not apply to NVP use in other settings. Single-dose \r\nNVP is one of the regimens recommended by PHS for prevention of perinatal HIV \r\ntransmission (7). No serious toxicity has been reported among mother-infant pairs using \r\nthis regimen. Combination antiretroviral regimens containing NVP may be used in HIV- \r\ninfected persons after weighing the risks and benefits and monitoring adverse \r\nreactions.\r\n\r\nHealth-care providers and the public can assist in monitoring the safety \r\nof antiretrovirals and other agents by reporting adverse reactions to the FDA \r\nMedWatch program: telephone, (800) 332-1088, fax, (800) 332-0178, World-Wide Web,\r\nhttp:\/\/www.FDA.gov\/medwatch, or mail, MedWatch, HF-2, FDA, 5600 Fishers Lane, \r\nRockville, MD 20857.\r\n\r\nReferences\r\n\r\n1.\tJohnson S, Baraboutis JG, Sha BE, Proia LA, Kessler HA. Adverse effects associated \r\nwith use of nevirapine in HIV postexposure for 2 health care workers [Letters]. \r\nJAMA 2000;284:2722--3.\r\n2.\tCattelan AM, Erne E, Slatino A, et al. Severe hepatic failure related to nevirapine \r\ntreatment. Clin Infect Dis 1999;29:455--6.\r\n3.\tSidley P. South Africa to tighten control on drug trials after five deaths. Br Med \r\nJ 2000;320:1028.\r\n4.\tCDC. Update: provisional Public Health Service recommendations for \r\nchemoprophylaxis after occupational exposure to HIV. MMWR 1996;45:468--72.\r\n5.\tCDC. Public Health Service guidelines for the management of health-care worker \r\nexposures to HIV and recommendations for postexposure prophylaxis. MMWR \r\n1998;47(no. RR-7).\r\n6.\tGuay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose \r\nnevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 \r\nin Kampala, Uganda: HIVNET 012 randomized trial. Lancet 1999;354:795--802.\r\n7.\tUS Public Health Service. Public Health Service Task Force recommendations for use \r\nof antiretroviral drugs in pregnant HIV-1 infected women for maternal health and \r\ninterventions to reduce perinatal HIV-1 transmission in the United States. Available at\r\n\r\nhttp:\/\/hivatis.org\/guidelines\/perinatal\/Nov_00\/text\/index.html. Accessed January 2001.\r\n8.\tWang SA, Panlilio AL, Doi PA, et al. Experience of healthcare workers taking \r\npostexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure \r\nProphylaxis Registry. Infect Control Hosp Epidemiol 2000;21:780--5.\r\n9.\tBell DM. Occupational risk of human immunodeficiency virus infection in \r\nhealthcare workers: an overview. Am J Med 1997;102:9--15.\r\n10.\tSoriano AP, Jim\u00e9nez-N\u00e1cher I, Rodriguez-Rosado R, Dona MC, Barreiro PM, \r\nGonz\u00e1lez-Lahoz J. Incidence of rash and discontinuation of nevirapine using two different \r\nescalating initial doses [Letter]. AIDS 1999;13:524.\r\n\r\n* Information included in this report does not represent Food and Drug Administration \r\napproval or approved labeling for the particular product or indications in question.\r\n\r\n\u2020 Use of trade names and commercial sources is for identification only and does not \r\nconstitute endorsement by CDC or the U.S. Department of Health and Human Services.\r\n","author":"Paul King","parent_id":120358,"mime_type":"text\/plain","created":"2004-12-29 01:48:04","modified":"2013-11-11 00:31:49","fileurl":""},{"id":120563,"heading":"AP: U.S. Officials Knew of AIDS Drug Risks","article":"AP: U.S. Officials Knew of AIDS Drug Risks \r\nMon Dec 13, 3:11 PM ET\r\n\r\n\u00a0White House - AP\r\nBy JOHN SOLOMON, Associated Press Writer \r\nWASHINGTON - Weeks before President Bush (news - web sites) announced a plan to protect African babies from AIDS (news - web sites), top U.S. health officials were warned that research on the key drug was flawed and may have underreported thousands of severe reactions including deaths, government documents show. \r\nAP Photo \r\nAP Photo \r\nSlideshow: HIV\/AIDS\r\n\u00a0\r\nThe 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. \r\nBut the National Institutes of Health (news - web sites), the government's premiere 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. \r\n"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 (news - web sites). \r\nThe 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 (news - web sites). \r\nNIH'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. \r\nLess than a month after Bush announced a $500 million plan to push nevirapine across Africa to slow the AIDS epidemic, the Health and Human Services (news - web sites) Department sent a nine-page letter to Ugandan officials identifying violations of federal patient protection rules by NIH's research. \r\nThe 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. \r\nAfrica accounts for more than two-thirds of the world's AIDS cases, with 27 million infected, and the United States sought to help slow the disease's spread across the continent. \r\nNevertheless, 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 (news - web sites) transmissions during birth. But they acknowledged their Uganda research failed to meet required U.S. standards. \r\nAs a result, NIH recently asked the National Academy of Sciences (news - web sites) to investigate its science in the case, and has spent millions in the last two years improving its safety monitoring and record keeping. \r\n"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. \r\nOne lesson derived from a closer review of the Uganda research is that even single doses of nevirapine can create instant resistance, meaning patients may not be able to use the drug or others in its class again when their AIDS worsens, Lane said. \r\n"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. \r\nLane said NIH officials were aware in spring 2002 about 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. \r\nThe White House \u2014 though unaware of the NIH concerns \u2014 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. \r\n"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," spokesman Trent Duffy said. \r\n\u00a0\r\nNevirapine 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 like liver damage and severe rashes when taken over time. \r\nIn 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. \r\nBut 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. \r\nBoehringer 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." \r\nBoehringer 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. \r\n"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. \r\nWestat 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. \r\nNIH 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 fully and quickly disclose them. \r\nOfficials said the problems began when NIH converted the research from determining the drug's usefulness to supporting FDA (news - web sites) approval for the drug. Paperwork in Uganda wasn't kept to the FDA standards, they said. \r\n"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." \r\nNIH officials reviewed the bad news in early March 2002. \r\nMeeting 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). \r\n"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. \r\nThe minutes quote an NIH official who visited Uganda as saying, "The site staff doesn't know what they don't know." \r\nBut 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. \r\n"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. \r\nIn January 2002, Boehringer sent NIH an early copy of its report. But the drug maker, fearing publicity about the report might destroy its chance to get the FDA approval of the drug for domestic use, asked NIH to destroy it before FDA regulators could learn about it. \r\n"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. \r\nBoehringer says it never requested the document be destroyed, saying "our actions throughout the study evaluation were proactive and forthcoming." \r\nLane 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." \r\nNIH 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. \r\nUnaware of the internal NIH concerns, Bush announced in June 2002 a $500 million effort to fight the spread of AIDS in Africa and the Caribbean. The plan's centerpiece was nevirapine. \r\n"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. The White House hoped the initiative would reach up to 1 million women a year and cut mother-to-child transmission of HIV by up to 40 percent. \r\nTwo years later, after hundreds of thousands of doses of nevirapine have been distributed to African mothers and children, the FDA has recommended NIH stop using the drug with certain patients. It also has demanded stronger warnings to doctors and patients about possible lethal liver damage and rashes in patients who take nevirapine for longer periods of time. \r\nAfrican 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. \r\nAfrican doctors said they weren't aware of the full extent of NIH's concerns but feel comfortable \u2014 at least until better options emerge \u2014 administering it in single doses to AIDS-sickened mothers who have few other choices to protect newborns. \r\n"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." \r\nBoehringer 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. \r\n"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. \r\nStill, the German-owned company no longer is seeking FDA permission to use nevirapine for protecting U.S. infants because better treatments have emerged, he said. \r\n___ \r\nAP reporter Alexandra Zavis in Johannesburg, South Africa, contributed to this story. \r\nOn the Net: \r\nDocuments gathered by AP for this story are available at: http:\/\/wid.ap.org\/nevirapine1.html \r\nNational Institutes of Health: http:\/\/www.nih.gov \r\nBoehringer Ingelheim: http:\/\/www.boehringer-ingelheim.com ","author":"Paul King","parent_id":120358,"mime_type":"text\/plain","created":"2004-12-29 01:50:14","modified":"2013-11-11 00:31:49","fileurl":""}]}