International AIDS Conference VIII: Reverse Transcriptase Inhibitors


International AIDS Conference VIII: Reverse Transcriptase Inhibitors

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

Stavudine (D4T). Stavudine has been found to be as potent as AZT but lacks bone marrow toxicity. Phase II data was presented (Bristol-Meyers protocol 455-006) in a group of 50 patients followed for at least 10 weeks on stavudine doses of 0.1, 0.5, or 2 mg/kg/day. The only significant improvement was that of decreased viral load in the patients on 2 mg/kg/day of the drug (Anderson, USA, WeB1010). A small study showed five of seven patients on a range of D4T doses eradicated plasma viremia by week 34, with the effect of the drug greatest at doses of 2mg/kg/day (Brett-Smith, USA, PoB3011). Another study was presented reviewing five Bristol-Meyers protocols addressing stavudine and clinical endpoints of CD4 count, death and frequency of side effects. The study analyzed 259 patients with CD4 counts below 500, with doses ranging 0.1-12 mg/kg/day. An overall 30 percent increase in CD4 count at three months. Among individuals whose CD4 counts rose more than 50 percent, the increase lasted a median of more than 12 months. Fifteen percent of the cohort progressed or died on therapy. As expected, side effects were related to the dosage level. The rate of reversible peripheral neuropathy in patients taking less than 2 mg/kg/day was similar to that of patients taking ddI. But the rate of peripheral neuropathy was 24 percent in patients taking more than 2 mg/kg/day. Other side effects were headache (2percent), and elevated liver function tests (11 percent). There were no comparison groups (Dunkle, USA, WeB1011).

FLT (3'-deoxy-3'-flourothymidine). FLT is a nucleoside RT inhibitor that is closely related to AZT but has been found to be 10 times more potent. A phase I trial of FLT in 10 symptomatic patients with CD4 less than 300 showed that a dose of 0.25 mg/kg/day was poorly tolerated, with nine patients developing anemia (Barditch-Crovo, USA, WeB1012). Only five patients completed 16 weeks of therapy. There was no change in CD4 count at the end of the study period, though three patients demonstrated a decrease of HIV in the blood (Polsky, USA, PoB3025).

3TC (2'-deoxy-3'-thiacytidine). 3TC is a nucleoside derivative which has good bioavailability and is effective against AZT- resistant HIV (i.e. no cross-resistance). A phase I/II, dose- escalating study followed 90 asymptomatic patients with CD4 counts below 400 for 24 weeks. At doses of 0.5-12 mg/kg/day, minor toxicity (headache, fatigue, diarrhea) was noted. Surrogate markers showed little change in CD4 count or p24 antigen (Van Leeuwen Remko, Netherlands, WeB1014).

U87-201E. A phase I study of U87-201E, a non-nucleoside RT inhibitor, in 18 patients using three doses (800, 1600 and 2400 mg/day) showed the drug was well tolerated at the two lowest doses. The main side effect was reversible liver function abnormality seen at the highest dose (Cox, USA, WeB1015). In another study, U87-201E was found to be effective against AZT- resistant HIV (Campbell, USA, PoA2300).

L697,661. The Merck, Sharp and Dome study comparing 50, 300 and 1000 mg/day of L697,661 to 500 mg/day AZT was presented. This protocol was tested in two groups of at least 60 subjects: one with asymptomatic patients having CD4 counts between 200 and 500 and the other with patients having CD4 counts of less than 200. There was an increased incidence of rash in patients taking L697,661 (24 percent) compared to AZT (6 percent). In both groups, CD4 count and p24 antigen initially improved but then returned to baseline by the end of the six-week study period. Increased p24 antigen in patients taking L697,661 closely correlated with development of genetic mutations in the HIV virus, indicating resistance to L697,661. The drug still retains possibility as a component of combination therapy (Saag, USA, WeB 1013).
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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.