Journal Article

The Safety, Efficacy, and Pharmacokinetic Profile of a Switch in Antiretroviral Therapy to Saquinavir, Ritonavir, and Atazanavir Alone for 48 Weeks and a Switch in the Saquinavir Formulation

Alan Winston, Patrick W. G. Mallon, Claudette Satchell, Karen MacRae, Kenneth M. Williams, Malte Schutz, Matthew Law, David A. Cooper and Sean Emery

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 44, issue 11, pages 1475-1483
Published in print June 2007 | ISSN: 1058-4838
Published online June 2007 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/517507
The Safety, Efficacy, and Pharmacokinetic Profile of a Switch in Antiretroviral Therapy to Saquinavir, Ritonavir, and Atazanavir Alone for 48 Weeks and a Switch in the Saquinavir Formulation

More Like This

Show all results sharing these subjects:

  • Infectious Diseases
  • Immunology
  • Public Health and Epidemiology
  • Microbiology

GO

Show Summary Details

Preview

Background. Toxicities observed with current combination antiretroviral therapy (CART) warrant a search for novel options, such as class-sparing regimens. Ritonavir-boosted double—protease inhibitor (PI)–only regimens are such an option but are prone to pharmacokinetic interactions.

Methods. This 48-week randomized study examined the safety and efficacy of a switch in CART to a once-daily regimen of saquinavir (SQV), ritonavir (RTV), and atazanavir (ATV) that did not include nucleoside reverse-transcriptase inhibitors (NRTIs). The study also assessed the pharmacokinetic profile of a change in the SQV formulation, from 200 mg to 500 mg, in 2 regimens (SQV-RTV twice per day plus NRTIs [arm 1] and SQV-RTV-ATV once per day without NRTIs [arm 2]) in human immunodeficiency virus type 1–infected subjects (plasma human immunodeficiency virus RNA level, <50 copies/mL). Patients underwent an initial SQV formulation change or a CART change to SQV-RTV-ATV with intense pharmacokinetic sampling. All patients were subsequently assigned to receive SQV-RTV-ATV (1500, 100, and 300 mg once per day, respectively) without NRTIs for 48 weeks. The primary end point was the percentage of patients who experienced virologic failure.

Results. Of 25 subjects enrolled, scleral icterus was the most common adverse event (3 patients [12.5%]). Three subjects (12.5%) experienced virologic failure; and mean (± standard error of the mean) increase in the CD4+ lymphocyte count was 63 ± 36 cells/µL over 48 weeks (P = .012). The SQV geometric mean area under the time curve parameters were not significantly altered for the 2 SQV formulations (arm 1, 23.32 vs. 18.76 ng × h/mL [geometric mean ratio, 0.80] for the 200-mg vs. 500-mg formulations, respectively; arm 2, 50.31 vs. 44.79 ng × h/mL [geometric mean ratio, 0.88], for the 200-mg vs. 500-mg formulations, respectively).

Conclusions. A CART regimen of SQV-RTV-ATV alone demonstrated sustained virologic efficacy and was associated with significant increases in the CD4+ lymphocyte count.

Journal Article.  4507 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.