International AIDS Conference VIII: Non-Reverse Transcriptase Inhibitors


International AIDS Conference VIII: Non-Reverse Transcriptase Inhibitors

Seattle Treatment Education Project: STEP Perspective - Volume 4, Number 3 - October 1992
Lori Panther, M.D.

Pentoxyfylline (Trental). Laboratory research found pentoxyfylline could inhibit HIV and could reduce tumor necrosis factor (TNF) levels (Steigbigel, USA, PoA2323). ACTG 160 was a phase I study of 25 patients with CD4 counts of less than 300 who were administered 1200 mg/day of pentoxyfylline. Eight patients did not finish the study. TNF levels did decrease during the study period of at least 16 weeks, but overall HIV blood titers did not change (Dezube, USA, MoB0019). Another in vitro study showed that pentoxyfylline enhanced the anti-HIV activity of ddI (Zhang, USA, PoA2326).

CD4PE40. CD4PE40 is a recombinant (i.e. genetically engineered) CD4 molecule attached to a bacterial toxin. Because CD4 binds to the gp120 molecule of the virus, this drug's action is due to the bacterial toxin's effect on a cell or virus bearing the gp120 molecule, such as HIV or an HIV-infected cell. A phase I single-dose escalating study of 25 patients was reported. Doses ranged from 1-240 g/kg intravenously. The maximum tolerated dose was 15 g/kg and the major side effect was reversible elevation in liver function tests (Davey, USA, MoB0020).

Tat antagonists. "Tat" is a gene in the HIV chromosome. The gene product of "tat" allows HIV to replicate. Theoretically, antagonists of tat would prevent replication of HIV. Previous studies of Ro24-7429, a compound related to valium, showed that it was active against both HIV-1 and HIV-2, was effective against AZT-resistant strains, and demonstrated no resistance. Ro24-7429 was studied in a phase I fashion in 18 patients over three doses: 60, 200, and 600 mg/day. Besides fluorescent yellow urine, there was no difference in side effects between drug and placebo (Petty, USA, MoB0021).

N-acetylcysteine (NAC). NAC is an amino acid derivative that inhibits a specific biochemical pathway needed for HIV replication. It has been shown to be effective against HIV in vitro. Two studies were presented regarding the antiviral properties of NAC in people with conflicting results. One study was presented by researchers in Barcelona, Spain. In this randomized trial, 16 individuals received 3000 mg of NAC intravenously for 15 days. Results showed a significant decrease in p24 antigen values in the group treated with NAC(PoB3013).

However, another study conducted in the United States showed no benefits. In this phase I/II trial, nine individuals with CD4 counts less than 500 were assigned to one of four dose level groups, ranging from 600 to 4800 mg orally per day, and from 3.7 to 100 mg/kg intravenously three times a week. Over the 14 week course of the study, there were no singificant changes in CD4 counts, p24 antigenemia, or plasma viremia. Because no serious toxicities were seen in any of the dosage levels, the National Institute of Health is considering increasing the dosages (Walker, USA, MoB0022). Obviously more studies are needed to assess the efficacy of NAC as an antiviral.
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Always watch for outdated information. This article first appeard in 1992. This material is designed to support, not replace, the relationship that exists between you and your doctor.

Copyright © 1992 - Seattle Treatment Education Project (STEP) - All rights reserved. Noncommercial reproduction is encouraged. STEP is published four times a year by the Seattle Treatment Education Project, 127 Broadway East, 3rd Floor, Seattle, WA 98102.    Email: step100@aol.com  STEP web page

This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1992. AEGIS.