Sustiva Analysis
While Sustiva will play an important role in HIV therapies, a close look at the Dupont Press Release indicates that Sustiva may not, in fact, replace PIs:
1) Study 020 indicated that Sustiva + two nucleoside analogues + Crxivan was better than two nucleoside analogues + Crixivan alone (75% versus 45% at 24 weeks). Undoubtably, the arm including Sustiva was superior. Note that Sustiva decreases blood levels of all PIs except for Viracept. Sustiva increases blood levels of Viracept by 20%.
2) Study 005 supposedly indicates that Sustiva may replace PIs, or "May therefore offer physicians and patients a new initial HIV treatment regimen." This study enrolled treatment naive patients only. Treatment naive patients' response rate to anti-HIV therapies has generally been superior to previously treated patients. The arm of the study cited in the Dupont press release highlights that "11 patients randomized to Sustiva (600 mg)/AZT/3TC who had reached the 36-week time point achieved HIV-RNA BQL." (Below Quantifiable Level) "Using a more conservative 36-week LOCF analysis, 82% of the patients in this arm achieved BQL."
Thes results seem remarkable until one goes back to the study design. The 600 mg arm above started with 34 patients. At 16 weeks, those patients who had a detectable viral load were switched from AZT to D4T, and Crixivan was added to their treatment regimens. At 24 weeks 26 of 34 patients remained on the study: 6 experienced an adverse event; 1 was dropped due to noncompliance; and 1 was lost to follow-up. By simple math we can calculate that 11 patients were non-detectable and 15 were detectable (assuming no patients left the study from 26 to 36 weeks.) More patients probably did leave the study. In summary, 11 of 34 (32%) treatment naive patients on the AZT/3TC/Sustiva arm achieved an HIV RNA non-detectable level at 36 weeks. Excluding those who we know left the study, 11 of 26 patients (42%), achieved an HIV RNA non-detectable level. The efficacy results are not comparable to Viracept and other PIs, which have demonstrated 80% and higher non-detectable levels, often in previously treated patients. In addition, Dupont's own study 020 (above), only 74% of patients taking Sustiva, Crixivan, and two nucleoside analogues achieved HIV-RNA BQL. |
