Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Clin Infect Dis. 2007 Jun 1;44(11):1475-83. Epub 2007 Apr 18.

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.

Author information

  • 1National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. a.winston@imperial.ac.uk

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/ mu L 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 ngxh/mL [geometric mean ratio, 0.80] for the 200-mg vs. 500-mg formulations, respectively; arm 2, 50.31 vs. 44.79 ngxh/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.

PMID:
17479946
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk