AEGiS-14IAC: Switch of saquinavir 400 mg/ritonavir 400 mg to saquinavir 1000 mg/ritonavir 100 mg during BID four drug antiretroviral therapy in patients with viral load less than 200 copies/ml.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Switch of saquinavir 400 mg/ritonavir 400 mg to saquinavir 1000 mg/ritonavir 100 mg during BID four drug antiretroviral therapy in patients with viral load less than 200 copies/ml.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. WeOrB1263)

O'Brien WA, Rojo D, Acosta E, Felizarta F, Pearce D, Jayaweera DT, Visnegarwala F
University of Texas Medical Branch, Galveston, TX, United States

BACKGROUND: Ritonavir (RTV) enhances saquinavir (SQV) exposure via inhibition of SQV hepatic metabolism. Durable viral load (VL) suppression has been demonstrated with SQV 400 mg/RTV 400 mg BID, but this regimen can be associated with hyperlipidemia as well as frequent adverse events, perhaps associated with the RTV dose used. PK and clinical outcome data support the use of RTV 100 mg BID to enhance SQV 1000 mg BID. We assessed the efficacy, plasma SQV/RTV, fasting plasma lipid levels, and tolerability after dose modification of combination SQV/RTV from 400/400 to 1000/100 in patients with VL suppression.

METHODS: Subjects (VL <200 copies/ml) who had been receiving RTV 400 mg/SQV 400 mg for at least 6 months without prior use of >1 other PI for more than 3 months, were randomized to continue current therapy or to switch SQV/RTV to 1000 mg/100 mg BID. Other ARV were not changed. Plasma SQV and RTV levels were measured at baseline, 1 and 6 months, and fasting plasma lipids were measured every 3 months.

RESULTS: 23 patients participated. No patients in the study had increases in VL >400 copies/ml through month 6. One month post-randomization peak and trough drug levels were obtained at 2.8 ± 0.4h and 12.4 ± 1.5h post dose, respectively. Values are shown for the two treatment groups in the Table. Three patients dropped out, one with pancreatitis, and one patient with a strong family history of cardiovascular disease had sudden death (age 46). [table: see text]In 1000/100 patients, between baseline and 6 mos, fasting triglyceride levels fell from 635 to 375 mg/dl (P=0.038), and cholesterol levels fell from 323 to 236 mg/dl (P>0.05). Improved tolerability was documented.

CONCLUSION: Modification of SQV-400/RTV-400 to SQV-1000/RTV-100 is safe and effective. There are significant reductions in triglycerides over six months, trends toward reduction in cholesterol levels, and improved tolerability, likely related to the reduction in ritonavir drug levels.

Keywords: AEGIS, Saquinavir, Ritonavir, Viral Load, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, Pharmaceutical Preparations, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic, Acid, CD4 Lymphocyte Count, Laboratory Techniques and Procedures, Capsules, Drug Combinations, 4-benzamido-4'-isothiocyanostilbene-2,2'-disulfonate, Human, therapy, drug therapy

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WeOrB1263