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

Winston, Alan, Mallon, Patrick W. G., Satchell, Claudette, MacRae, Karen, Williams, Kenneth M., Schutz, Malte, Law, Matthew, Cooper, David A. and Emery, Sean (2007) 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. Clinical Infectious Diseases, 44 11: 1475-1483. doi:10.1086/517507


Author Winston, Alan
Mallon, Patrick W. G.
Satchell, Claudette
MacRae, Karen
Williams, Kenneth M.
Schutz, Malte
Law, Matthew
Cooper, David A.
Emery, Sean
Title 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
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1058-4838
1537-6591
Publication date 2007-06-01
Sub-type Article (original research)
DOI 10.1086/517507
Open Access Status Not yet assessed
Volume 44
Issue 11
Start page 1475
End page 1483
Total pages 9
Place of publication Cary, NC, United States
Publisher Oxford University Press
Language eng
Formatted abstract
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 x h/mL [geometric mean ratio, 0.80] for the 200-mg vs. 500-mg formulations, respectively; arm 2, 50.31 vs. 44.79 ng x 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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