336   Preliminary Results from Indinavir (IDV) and Ritonavir (RTV) in a Once-Daily Regimen (Marck 103/104).

J. Suleiman*, R. Rhodes, R. Campo, P. Piliero, R. Steigbigel, J. Chen, G. Winchell, and A. Saah.
Inst. de Infectologia Emilio Riba, Sao Paolo, Brazil and Merck Res. Labs., West Point, PA.

Background:Previously reported pharmacokinetic (PK) studies have demonstrated a favorable IDV profile using IDV/RTV once-daily.

Methods:Open-label, phase II, 48-week study of IDV/RTV 1200/200 q.d. with d4T + 3TC b.i.d. in treatment naive patients.

Results:40 patients enrolled. Steady state PK results were available from 9 patients. Geometric means (90% CI) were AUC_24h116mM•hr (102, 131), C_max17.9mM (16.2, 19.8), and C_24h156 nM (84, 292). Geometric mean baseline viral load was 69,581 (n=40) (range: 3,464 to 3,418,033) and mean baseline CD4 number (n=35) was 297 (range: 51 to 521). Table shows observed percent of patients with HIV-RNA <400 copies/mL and mean change in CD4 number in patients with available follow-up at 16 to 24 wks.

There were 6 discontinuations, none due to adverse events or virological failure. There was one serious adverse event unrelated to drug; no episodes of nephrolithiasis were reported.

Conclusion:Viral suppression, CD4 changes and PK profile with IDV/RTV once-daily is comparable to standard IDV 800 mg q8h and is generally well tolerated. A new arm of patients using IDV/RTV 1200/400 is being recruited to study further enhancement of IDV PK and potential tolerability differences from the IDV/RTV 1200/200 arm.