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MIKADO: a multicentre, open‐label pilot study to evaluate the antiretroviral activity and safety of saquinavir with stavudine and zalcitabine
Author(s) -
Katlama C,
Pellegrin JL,
Lacoste D,
Aquilina C,
Raffi F,
Pialoux G,
Vittecoq D,
Raguin G,
Lantz O,
Mouroux M,
Calvez V,
Trylesinski A,
Montestruc F,
Dohin E,
Goehrs Jm,
Delfraissy Jf
Publication year - 2001
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1046/j.1468-1293.2001.00046.x
Subject(s) - stavudine , saquinavir , medicine , tolerability , zalcitabine , interquartile range , indinavir , lamivudine , viral load , gastroenterology , protease inhibitor (pharmacology) , virology , pharmacology , drug holiday , adverse effect , human immunodeficiency virus (hiv) , virus , antiretroviral therapy , hepatitis b virus
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) log 10 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) log 10 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.