The Body Covers: The 5th Conference on Retroviruses and Opportunistic Infections
Sessions 50 and 51: Advances Made Towards Simpler Protease Inhibitor Regimens
February 3, 1998
Poster session abstracts 374 and 393Promoting adherence to difficult combination drug regimens continues to be a major concern of both doctors and patients. The conference had several presentations on simpler dosing schedules that show promise, but which need further study.
One study presented by Nguyen, et al., (#374) sought to evaluate the safety and efficacy of using indinavir at a 1200 mg dose every 12 hours (instead of the currently recommended 800 mg dose every 8 hours), in combination with AZT and 3TC in their standard doses. This was an open-label trial enrolling 88 patients with T-cells between 150 and 500, a viral load of at least 10,000 copies, and who had never taken a protease inhibitor nor 3TC. This is an ongoing year-long pilot trial. The study presented data on the 45 patients who have reached the 32 week point.
In the twice a day group, 10 of 14 patients (71%) had undetectable virus at week 32; 7 out of 12 (58%) experienced a viral load decrease to below 50 copies/ml. These results were comparable to what was seen in the standard dosing arm. A third arm of the study gave patients AZT/3TC with 1000 mg of indinavir every 12 hours. This arm's results were similar to those found in the 1200 mg every 12 hour group. Side effects were similar for all three groups, the most frequent being nausea and vomiting.
This is a preliminary study, and Merck (the makers of indinavir) is currently running a larger study to confirm these results.
A second combination study by Havlir et al., of indinavir at a lower dose than usual -- 1000 mg every 12 hours -- and nelfinavir (at first 750 mg, increased to 1000 mg, every 12 hours) showed that twice daily dosing of this double protease inhibitor combination is safe, and shows early signs of effectiveness. The study enrolled 21 patients with viral load levels over 30,000 copies/ml and CD4 cell counts over 100 cells/mm3. 58% of patients had never received antiretroviral therapy, while 42% had received treatment with one or more of the 'nukes' (AZT, ddI, ddC, d4T, 3TC). No previous protease inhibitor use was allowed.
The study's primary goal was to measure the levels of each drug in the blood, not necessarily to show anti-HIV activity, although some very early data on viral load decreases were shown. Most importantly, the data showed that nelfinavir increased blood levels of indinavir, thus raising the possibility of effective twice-daily dosing. Of the five patients who have reached week 32, four have undetectable viral load levels (below 400 copies/ml).
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