32

p Protease inhibitors are a new class of AIDS drugs used in conjunction with older chemotherapy compounds such as AZT and ddl. The mixture of these treatments is called a “combination cocktail" or “highly active antiretroviral therapy" (HAART). The formula is usually two parts nucleoside analog to one part protease inhibitor. According to popular belief, this mix brings new power to the old chemotherapies, and achieves what press reports and AIDS groups characterize as unprecedented and amazing results.

p Approved after the fastest and most lenient review process in FDA history and immediately hailed as miraculous by mainstream media, the clinical benefits of protease inhibitor drugs remain unproved. More than four years after being released for use, there are still no reports in scientific journals that provide evidence of health improvement in patients taking these powerful drugs.

p Claims of victory for protease inhibitors are based entirely on changes in surrogate markers, laboratory measurements of unsubstantiated accuracy and value in assessing actual health. In the only published report alleging higher survival rates for patients treated with protease inhibitors, the study used no unmedicated placebo controls, did not allow reporting of any recurrent AIDS-defining events except pneumonia, included no patient data, cited outcomes for less than 10% of overall participants, and was prematurely terminated after an average follow-up of 38 weeks when emerging mortality statistics favored the protease inhibitor treated patients.^^115^^ The survival outcomes between the two groups—1.4% mortality among those on the new drugs, 3.1% for the old drugs—have no statistical significance, a fact that forces the drug advertisements to admit “because the study was ended early, there was insufficient data to determine the statistical impact of Crixivan on survival.”^^117^^

p One National Institutes of Health study of protease inhibitors, ACTG 315, is portrayed as a success even though its conclusions are drawn from a trial of only 12 weeks.^^118^^ Dr. Michael Lederman, protocol chairman and author of ACTG 315 acknowledged that the study was never designed to consider a patient’s health. Instead, results were determined by changes in the surrogate marker of “viral load,” a test that does not diagnose illness, quantify active virus or measure health.

p The absence of data on long-term effects of protease inhibitors has not prevented orthodox AIDS organizations who promote or provide the drugs from becoming uncritical advocates. Following the lead of the media, their focus has been on securing widespread access to the treatments rather than on examining evidence to insure they are safe and effective. AIDS doctors have also overlooked the

---

33 remarkable lack of documentation in favor of the options for treatment offered by protease inhibitors. And while boldface headlines continue to assign lifesaving properties to these drugs, the tiny type in pharmaceutical ads, the ever-growing list of side effects, and the increasing number of unsuccessful experiences—ranging from physical deformities to sudden death—tell an entirely different story.

p Protease inhibitors are assumed to work by disrupting an enzymatic link in the reproduction of HIV Enzymes are proteins that join together or cut apart other molecules. Like all retroviruses, HIV has three enzymes: reverse transcriptase, integrase, and protease which cut proteins apart, an essential step in the reproductive process of a retrovirus. Protease inhibitors block proteases by acting as dysfunctional molecules that take the place of functional ones and inhibit the cutting apart of proteins. All retroviral enzymes are similar to various human enzymes and there are numerous human proteases, including ones required for digestion of food.

p Protease inhibitors are like nucleoside analog drugs such as AZT in that they produce dysfunctional substitutes that interrupt or prevent normal processes of enzymes. While manufacturers of protease inhibitors claim that the drugs specifically target HIV protease, the growing list of side effects contradicts their assertions. Nucleoside analogs such as AZT, once promoted as specifically targeting HIV, have been shown to block the construction of vital human DNA as effectively as they block the formation of HIV DNA. It is now known that AZT, ddl and other nucleoside analogs block the DNA inside mitochondria, the subcellar particles that produce the energy required for the life of all cells.

p The necessity for lifelong therapy with protease inhibitor cocktails is described as absolute, although drug manufacturers clearly state that “the long-term effects of protease inhibitors are unknown.” The need for rigorous compliance with combo therapy is a popular subject of news reports and AIDS organization seminars. Patients are required to pop as many as 30 pills a day on a 24 hour schedule—some taken with food, others on an empty stomach, many that cannot be taken together—and warned that without strict adherence to the dosages and times, their virus will mutate into new, drug resistant strains.

p According to Dr. David Rasnick, a protease expert working outside the AIDS system, the theory of resistant HIV protease is completely unfounded. Rasnick, a pioneer in the development of protease inhibitors points out, “no one has ever published data on a resistant HIV protease found in any patient. The only inhibitor-resistant HIV proteases ever examined have been produced in the lab using genetic engineering.”^^119^^

p Nevertheless, warnings about drug-resistant HIV proteases are emphasized in media reports that also speculate about new epidemics that will arise when unstoppable forms of HIV are introduced into the population. As announced by AIDS researcher Dr. Bruce Walker on a recent segment of ABC News’ Nightline, “That’s going to be the next epidemic that we’re dealing with, the transmission of drug resistant HIV viruses.”^^120^^ Such reports reinforce the notion that no matter how unbearable the side effects, a patient who quits the drugs becomes a public health menace. This science-fiction scenario has even inspired some health officials and legislators to consider mandatory treatment laws for HIV positives.^^121^^

34

p Perhaps the greatest achievement of protease inhibitors is the new life they have given to AIDS advertising campaigns. An epidemic of posters, billboards, and full-page magazine ads urge HIV positives to “be smart about HIV" by “hitting early and hard" with medicines “proven to help people live longer, healthier lives.”^^122^^ However, many staunch supporters of AIDS pharmaceuticals are less certain. Top AIDS scientist Dr. Anthony Fauci expressed serious reservations about the use of protease inhibitors by “otherwise healthy people" in a recent article in the Journal of the American Medical Association, “We do not know whether early intervention in asymptomatic individuals will result in a long-term clinical benefit or whether the cumulative toxicity over years of drug administration will outweigh the potential benefits.”^^12^^’ Even Dr. Robert Gallo has warned that “these drugs are toxic. ..the longer you take the drugs, the greater the toxicity.”^^124^^ Dr. Jay Levy, another mainstream AIDS specialist, maintains that “these drugs can be toxic and can be directly detrimental to a natural immune response to HIV"^^125^^

p A careful examination of the small pnnt in protease inhibitor ads puts the promises made by smiling models into perspective: “Since Crixivan has been marketed, other side effects have been reported including rapid breakdown of red blood cells, kidney stones and kidney failure. In some patients with hemophilia, increased bleeding has been associated with protease inhibitor use.”^^126^^ Premarketing side effects like diarrhea, nausea, fungal infections, bloody urine, weakness, headaches and liver inflammation were all but ignored by AIDS activists who pressured the FDA for fast-track approval.^^127^^ The list of post-marketing side effects continues to grow and contradicts earlier reports on the cocktails that proclaimed, “Its unbelievable. There’s no toxicity. It’s a home run!”^^128^^

p Documented adverse reactions presently include CMV retinitis (a viral infection that often results in blindness), diabetes, liver failure, physical deformities, renal failure, kidney sludge, skin rashes, severe exhaustion, loss of appetite, pancreatitis, diarrhea, nausea and vomiting, muscle and joint pain, neuropathy, sexual dysfunction, fever, chills, dizziness, abdominal pain, depression, sleep disorders, and sudden death.^^129^^

p Other than anecdotal tales of miraculous recoveries trumpeted in the press, the lower levels of “viral load" found in some patients taking protease cocktails seem to be the only and highly questionable result of these treatments. But even “undetectable” viral loads are not an unprecedented occurrence in HIV treatment—AZT has lowered those levels for many years without resolving AIDS. A POZ magazine article recalls that “in the European Delta study, fully 40% of participants became ‘undetectable’ [for viral load] on AZT/ddl; another 5% did so on AZT alone. We have been reducing viral load to undetectable levels for a decade. But if becoming ‘undetectable’ on nucleoside combos hasn’t prevented progression to disease and death, why is ‘undetectable’ on protease combinations impervious to failure—except for the fact that we haven’t followed patients long enough to see it?”^^130^^

Although the media credits “AIDS cocktails" with recent decreases in AIDS cases and deaths, CDC surveillance reports clearly show that AIDS cases and mortalities began declining before the cocktails were approved for use.^^131^^

---

35

p Some experts attribute the drops in AIDS deaths to the fact that over half of all AIDS cases reported since 1993 are among people who test HIV positive but have no illness or symptoms.^^132^^ The same reports show that AIDS cases had leveled off in 1991 and increased only once since, in the first quarter of 1993 when more conditions and illness were added to the definition of AIDS.

p For some, the chorus of enthusiastic press reports about protease inhibitors recalls the release of AZT twelve years ago. “Once again, all we have are researchers talking to reporters about incomplete studies that haven’t been scrutinized by the scientific review process,” remarks Dr. Rasnick. “And the researchers involved are funded by the companies that make the drugs in question. There is no justification for the claims coming from these sources, particularly when we’ve seen it all before.”^^133^^

p Declarations of success and improved survivability for AZT were based on abbreviated trials of less than six months duration that were sponsored by the drug’s manufacturer who selected for publication only those trials with seemingly favorable outcomes. Success was measured by the surrogate marker of that day, increased T cell counts, which have proved to be a temporary phenomenon at best and of questionable clinical value. As with AZT, the elation unleashed over protease inhibitors is based on unpublished manufacturers’ studies so brief they are usually measured in weeks rather than months, and on the surrogate marker of reduced “viral load,” a measurement that has not been correlated with actual health benefits. While the media persists with stories of the miraculous achievements of protease inhibitors making believers out of the concerned public and desperate AIDS patients, only time and independent research will reveal the truth about the latest “great hope" in the war on AIDS.

p Reasons to Wonder About the Wonder Drugs^^194^^

p > There are no long-term studies that demonstrate health benefits or increased life expectancy for patients taking the drug combinations known as HAART.

p > Studies show that HAART actually shuts down numerous functions of the immune system considered essential for survival including the activity of many cytokines, proteins that trigger vital immune responses.

p > 30% of patients taking HAART suffer from lipodystrophy, a fat distribution and metabolic disorder that can lead to heart attacks and strokes, and cause fat lumps known as “buffalo humps" and other physical deformities.

> The decreased levels of viral load that occur in some patients taking HAART do not correlate with wellness, increased T cells or improved rates of survival.