Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir, and indinavir: Adult AIDS Clinical Trial Group Study 398.

The present population pharmacokinetic (PK) and pharmacodynamic (PD) study modeled the effects of covariates including drug adherence and the coadministration of protease inhibitors (PIs) on the pharmacokinetics of efavirenz (EFV) and the relationship between EFV exposure and virological failure in patients who failed initial PI treatment in Adult AIDS Clinical Trial Group (AACTG) study 398. We also report on the population PKs of the PIs nelfinavir (NFV) and indinavir (IDV). AACTG study 398 patients received EFV, amprenavir, adefovir dipivoxil, and abacavir and were randomized to take, in addition, one of the following: NFV, IDV, saquinavir (SQV), or placebo.

Baseline predictors of CD4 T-lymphocyte recovery with combination antiretroviral therapy.

CD4 T-cell recovery with potent antiretroviral therapy varies considerably among HIV-1-infected patients. Data from two studies that enrolled subjects at different stages of disease progression were retrospectively combined. This analysis assessed the association between patient-specific factors and three measures of CD4 T-cell recovery after the initiation of triple-drug therapy: overall changes in CD4 cell counts; changes in CD4 cell counts during the first 8 weeks (phase I); and changes in CD4 cell counts during weeks 8-24 (phase II).

Effect of coadministration of nelfinavir, indinavir, and saquinavir on the pharmacokinetics of amprenavir.

Objective: Pharmacokinetic interactions are expected when human immunodeficiency virus (HIV) protease inhibitors are coadministered because many are both substrates for and inhibitors of CYP3A4. The goal of this model-based pharmacokinetic analysis was to describe the differences observed in amprenavir pharmacokinetics among treatment arms in the Adult AIDS Clinical Trial Group (AACTG) study protocol 398 and to propose mechanisms to account for them.

Methods: One hundred seventy-six HIV-positive subjects receiving 1200 mg amprenavir twice daily as part of AACTG protocol 398 were included in the pharmacokinetic study.

Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.

Context: Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge.

Objective: To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen.

Design: Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks.