The following letter by Udo Schueklenk was submitted to Brother Sister in Melbourne.
Clinical researchers at the US National Institute of Health (NIH) recently conducted a trial to test a drug, FIAU, supposed to combat hepatitis B virus. Four patients died of liver failure, several others in the 20 person trial experienced serious problems after receiving this drug over a three-month period. As the Journal of NIH Research revealed in its September issue, FIAU structurally resembles deoxythymidine, and like other nucleoside analogues (such as AZT) it inhibits DNA replication. FIAU functions similarly to AZT.
Jay Hoofnagle of the US National Institute of Diabetes and Digestive and Kidney Disease, the principle investigator of the FIAU trial, warned: "We are concerned about the usual toxicities associated with nucleoside analogues, including neuropathy and myopathy (both of which are often observed in AIDS patients taking AZT)".
Yale University's Yung-chi Cheng wasn't surprised about the dramatic failure of the FIAU trial. He warned of the potential of nucleoside analogues to damage mitochondria irreversibly as early as 1989, when he was able to show that similar viral inhibitors can interfere with mitochondrial DNA replication. He said "I am surprised that the effects of FIAU on mitochondria were never assessed. Nobody has paid attention to mitochondrial DNA synthesis in the past. But as these drugs that inhibit viral DNA replication [such as AZT] are being used in long-term treatment ... [it becomes] a problem that needs to be addressed".
The article in the Journal of NIH Research continues reporting that several other antiviral drugs being used to treat AIDS patients may be exerting a similar toxic effect in people receiving long-term therapy. In the March 1993 issue of AIDS, Joel Freiman of the US Food and Drug Administration and colleagues reported eight cases of liver failure in HIV-1 infected patients receiving AZT. The major toxic effects of AZT, ddC, and ddl include damage to the skeletal muscle, the pancreas, blood cells and the peripheral nervous system. As early as 1990, US scientists reported that the muscle myopathy found in patients taking AZT for prolonged periods may be due to damage to skeletal muscle-mitochondia.
A large number of studies revealed recently that AZT, ddC, and ddl may induce liver damage as well. It has been reported by Freiman and associates that persons infected with HIV-1 who had not developed AIDS, and who had been treated with AZT for more than six months, developed hepatic failure with severe steatosis. The NIH report continues, "Six of the patients died, two did not".
This is not a bad record for a drug which is supposed to prolong the disease-free period of life for infected persons, and even prolong the lives of persons with AIDS, is it? If one was a cynic, one could even argue that those people didn't die of AIDS, therefore AZT was somewhat successful in preventing AIDS. "There appear to be many similarities in cases of AZT and FIAU toxicity", says Freiman.
By June 1993, the US Food and Drug Agency asked Burroughs Wellcome to send a letter to 12,000 infectious disease doctors warning them about the problem. Last month the same letter went out to a more general audience of 194,000 other physicians, as concerns grew. What has really brought the issue of these potentially fatal side effects of AZT and other nucleoside analogues into the news is the sudden death of five out of the seven FIAU clinical trial participants who received the full 30 day regimen of that drug.
The Washington Post has, in a series of articles, broken the silence on the previously unexplained side effects of nucleoside analogues.
It is unlikely that disturbing revelations such as these will have a great impact on the Australian AIDS organisations' advertising frenzy for AZT, ddC and ddl, or on the Australian AIDS research establishments changing their policies on AZT. Both have spent the last years propagating every study on AZT as another proof of how wonderful this drug is, while at the same time ignoring the significant body of empirical evidence questioning each of their standard claims, i.e. that AZT prolongs the disease-free period of life and that it prolongs life.
While the Concorde study has already had a significant impact on the prescription of AZT in Europe and in the USA, Australia still seems to be on the 'early intervention with AZT trip'. The information revealed in the Journal of NIH Research article shows why AZT, ddC, and ddl are a dead end.
(Thanks to Billi Goldberg of ACT UP San Francisco for supplying the information on the FIAU trials.)