Research Initiative Treatment Action (RITA!); Vol 5, No. 1 January 1999
The AIDS Clinical Trials Group (ACTG) will study the effects of OPTIMUNE on wasting. OPTIMUNE, distributed by Optim Nutrition, Inc., is a nutritional supplement containing a patented whey protein concentrate. The study will take place at 10 different sites across the United States and begin within the next few months. The study will be a randomized, double-blind trial that is designed to be a comprehensive evaluation of protein metabolism and its effect on body composition. Wasting is the second leading HIV/AIDS related cause of death in the United States.
A live teleconference, "Altered Body Shape in HIV Disease: A Side Effect of Therapy?" discussed the phenomenon recently described by various names such as fat redistribution, lipodystrophy, buffalo hump, etc. An expert panel warned that not only is the syndrome widespread but that it is also a serious health concern. Many believe that the syndrome which can manifest itself as a loss of fat and muscle in the arms and legs, an increase in abdominal fat, fatty deposits at the base of the neck, severe wrinkling of the face and enlarged breasts in women is caused by protease inhibitor therapy. These abnormalities are sometimes accompanied by elevated glucose levels and extremely elevated lipid levels that can significantly increase the risk of cardiovascular disease. An audio recording of the teleconference for playback is available by calling 888-207.2647, access code 1967. An edited transcript is published on the Internet at www.HIVTreatmentLive.com
The January 25, 1999 issue of The Wall Street Journal reported on a treatment phenomenon being followed by a number of physicians and researchers around the world. The inquiry begins with the now famous "Berlin patient" whose story was first reported in the New York Times Magazine. This patient began anti-HIV therapy, was virally suppressed, then stopped the therapy twice due to medical complications. He finally stopped therapy when the he could no longer tolerate the nausea. As of the World AIDS Conference in Geneva the Berlin patient had remained disease-free for 18 months, with only tiny residues of virus in his blood. Since that time, similar cases have been reported by others. Scientists are now looking at the possibility that this starting and stopping of therapy may have acted as a form of self-inoculation, priming the body with the defenses necessary to fight the returning virus. Scientists warn that the ultimate outcome of this scenario is not known and the exact circumstances producing this phenomenon are yet to be delineated.
Dutch scientists followed 78 patients treated with highly active antiretroviral therapy (HAART) who had stopped taking prophylaxis therapy for Pneumocystis carinii pneumonia (PCP). All patients had greater than 200 CD4 T cells. After a mean follow-up of 12.7 months none of the patients had developed PCP.
Scientists at the Fred Hutchinson Cancer Research Center and at the University of Washington are evaluating a form adoptive immunotherapy in which the patient's own HIV-specific cytotoxic T lymphocytes (CTL) are expanded outside the patient's body and are reinfused into the patient in an effort to boost the body's own immune system. Adoptive therapy had been tried before but has failed because scientists have never been able to expand CTLs and maintain their anti-HIV specificity. In addition, the transferred cells tend to die out quickly. The process used to expand cells in culture is known as Rapid Expansion Method (REM) and is capable of expanding great number of cells. Scientists are now investigating methods for making them live longer.
Researchers at Washington University School of Medicine in St. Louis have been conducting experiments using large proteins to attack HIV. They have designed proteins that activate the system of programmed cell death known as apoptosis. Apoptosis is the immune system's way of eliminating unneeded cells. The large protein designed by the scientists is called caspase 3 and its activation triggers apoptosis. Once inside a cell, caspase 3 is activated by the scissor-like function of the protease enzyme—the same function that is jammed by the action of protease inhibitors. In the test tube, scientists report, the reaction is so quick that all HIV-infected cells die within 10 minutes. It is believed that the same method could be used to eliminate other pathogens that use specific protease actions, such hepatitis C and cytomegalovirus.
A Swiss study reported in the December issue of AIDS indicates that most HIV-infected mothers and half of their children receiving combination therapy develop one or more adverse effect. Thirty-seven women and 30 infants who received combination therapy were evaluated. Among the mothers, 15 experienced anemia, 4 showed transaminase (liver function) elevation and 4 had nausea and vomiting. Ten children were premature, 8 had anemia, 2 showed angioma (tumor), 2 had cryptochidism (failure of testes to descend) and one had transient hepatitis.
Much has been made of a patient's need to adhere precisely to anti-HIV regimens. In a letter to the editor of the Journal of the American Medical Association, Peter J. Ungvarski of the Visiting Nurse Service of New York, cites a study of 202 HIV-infected patients which found that 40% of prescriptions to those patients had incorrect dosing schedules, suboptimal dosages and/or protease inhibitors ordered as monotherapy.
The U.S. Food and Drug Administration (FDA) recently enacted rules that require pharmaceutical companies to provide physicians with specific information on the effects of medication on children and under "compelling circumstances" to require pediatric testing of certain drugs. In addition, the FDA has approved nevirapine (Viramune) for use in HIV-infected children. nevirapine is the first non-nucleoside reverse transcriptase inhibitor (NNRTI) to be approved for children. One study found that 16% of children develop a drug-related rash. Finally, an advisory panel of the FDA recommended approval of Panretin (9-cis retenoic acid)gel, produced by Ligand Pharmaceuticals as a second line treatment of Kaposi's sarcoma.
The American Journal of Respiratory Critical Care reports a study that found cigarette smoking may decrease lung defenses against infection by suppressing the percentage and absolute number of CD4 T cells and CD8 cells.
The Lancet reports that HIV-infected women may have a higher risk of progressing to AIDS than HIV-infected men with the same viral load (plasma HIV RNA). Researchers from the Johns Hopkins School of Hygiene and Public Health and the National Institute of Allergy and Infectious Disease studied 812 specimens from 650 HIV-infected injection drug users and found that women had lower median viral loads than men, yet men and women had statistically similar time to AIDS. Women had a similar time to AIDS as men with viral loads that were twice as large. Scientists suggest initiation of anti-HIV therapy for women at a lower viral load may be justified.
Calanolide is a naturally occurring non-nucleoside reverse transcriptase inhibitor that has been synthesized from a Malaysian rain forest tree. In the test tube it is reported to be highly active against wild type HIV and zidovudine-resistant HIV. A dose-ranging study to evaluate the safety, pharmacokinetics and effects on viral load of calanolide on antiretroviral naïve patients is currently recruiting at the University of Texas Medical Branch in Galveston. The resistance profile of the drug is unknown. Interested parties should contact Phyllis Galatas at 409.747.0241.
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Copyright © 1999 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org
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