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Antimicrobial Agents and Chemotherapy, June 2007, p. 2035-2042, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01136-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Clinical and Pharmacokinetic Data Support Once-Daily Low-Dose Boosted Saquinavir (1,200 Milligrams Saquinavir with 100 Milligrams Ritonavir) in Treatment-Naive or Limited Protease Inhibitor-Experienced Human Immunodeficiency Virus-Infected Patients{triangledown}

Ana Marin-Niebla,1* Luis Fernando Lopez-Cortes,2 Rosa Ruiz-Valderas,2 Pompeyo Viciana,2 Rosario Mata,2 Alicia Gutierrez,2 Rosario Pascual,2 and Magdalena Rodriguez2

Hematology Department,1 Infectious Diseases Unit, Hospital Universitario Virgen del Rocio, Seville, Spain2

Received 10 September 2006/ Returned for modification 28 February 2007/ Accepted 14 March 2007

We evaluated the plasma and intracellular pharmacokinetics, clinical efficacy, and safety of once-daily low-dose boosted saquinavir (SQVr; 1,200 of saquinavir [SQV] with 100 mg of ritonavir) plus two nucleotide reverse transcriptase inhibitors in treatment-naive or limited protease inhibitor (PI)-experienced human immunodeficiency virus (HIV)-infected patients. A prospective study without entry restrictions on the plasma HIV-RNA (VL) or CD4 cell count was carried out. Plasma and intracellular SQV levels were measured by high-performance liquid chromatography. Efficacy was evaluated by an intention-to-treat analysis; treatment failure was defined as virological failure (a VL of >50 copies/ml after 24 weeks or a confirmed rebound to >50 copies/ml) or interruption for any reason. A total of 151 patients were included in the study (106 of them either had never received PI or had no previous virological failure on PIs) and could be characterized as follows: previous C3 stage, 28.9%; injection-drug users, 69.1%; subjects with chronic viral hepatitis, 53%; and subjects with cirrhosis, 10%. The median baseline CD4 level was 184/µl, and the median VL was 4.8 log10 copies/ml. Median Cmax, area under the concentration-time curve from 0 to 24 h, and Cmin plasma and intracellular SQV levels were 3,672 and 10,105 ng/ml, 34,283 and 99,535 ng·h/ml, and 359 and 1,062 ng/ml, respectively. The efficacy as determined by intention to treat at 52 weeks was 69.7% (96% in the on-treatment analysis), with similar results regardless of the baseline VL and CD4 counts. Only five patients had virological failure despite adequate Cmin levels, but with a poor adherence (the only variable related to virological failure). Adverse events caused the withdrawal of the treatment in four patients (2.6%). In conclusion, given the pharmacokinetic profile, efficacy, and tolerability of this regimen, once-daily low-dose SQVr may be considered a treatment option in treatment-naive or limited PI-experienced HIV-infected patients, with the additional benefit of being currently the least-expensive PI-based regimen available.

* Corresponding author. Mailing address: Servicio de Hematología, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Seville, Spain. Phone: 34 650470270. Fax: 34 955013265. E-mail: amniebla{at}telefonica.net

{triangledown} Published ahead of print on 19 March 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 2035-2042, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01136-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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