MIKADO: a multicentre, open-label pilot study to evaluate the antiretroviral activity and safety of saquinavir with stavudine and zalcitabine

Background  Since eradication of HIV is unlikely, long-term management of the disease necessitates careful evaluation of the combinations of currently available drugs to determine the most potent and useful rational sequencing of regimens. Objective  To determine the antiretroviral efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) plus zalcitabine (ddC) and stavudine (d4T), as first-line treatment in HIV-infected patients. Design  Multicentre, open-label, non-comparative study. Patients and methods  Thirty-five asymptomatic, HIV-infected adults with no prior antiretroviral treatment, a CD4 count ≥ 250 cells/μL and baseline ≥ 5000 HIV RNA copies/mL were included in the study. Patients received SQV-SGC 1200 mg three times a day (tid), ddC 0.75 mg tid and d4T 30 or 40 mg twice a day (bid) for 24 weeks. Plasma HIV RNA, CD4 and CD8 cell counts, HIV reverse transcriptase and protease resistance genotypes, SQV plasma concentration and tolerability were evaluated. Results  At baseline, median HIV RNA (interquartile range) was 4.99 (4.81–5.48) log10 copies/mL, and median CD4 count was 370 (318–504) cells/μL (n = 35). At week 24, the median decrease in HIV RNA was 3.05 (2.19–3.68) log10 copies/mL. A viral load below the level of quantification (200 copies/mL and 20 copies/mL) was achieved in 63% and 34% of patients, respectively (intent-to-treat analysis). The only mutations detected were L90M substitutions in two patients. At week 24, the median CD4 count increased (P < 0.0001), and CD8 cell counts decreased (P < 0.0001), relative to baseline. In total, there were five cases of peripheral neuropathy (14%). Mean triglyceride and cholesterol levels remained within normal ranges. Conclusions  Triple therapy with SQV-SGC plus ddC and d4T is a reasonably well tolerated regimen that markedly and rapidly reduces viral load with immunological improvement. This combination is an effective additional therapeutic option, with an efficacy that compares favourably to other triple regimens used in HIV treatment.