Interindividual variability in the effect of atazanavir and saquinavir on the expression of lymphocyte P-glycoprotein.

Objectives: ABCB1 encodes the efflux transporter P-glycoprotein (P-gp), which regulates the intracellular concentration of many xenobiotics, including several HIV protease inhibitors (PIs). Exposure to some xenobiotics, such as the antibiotic rifampicin, increases P-gp expression. In the present study, we investigated the effect of the HIV PIs saquinavir and atazanavir on the expression and function of ABCB1 and P-gp in primary and cultured lymphocytes, as well as the molecular interactions between these drugs and P-gp.

Pharmacokinetics of saquinavir with atazanavir or low-dose ritonavir administered once daily (ASPIRE I) or twice daily (ASPIRE II) in seronegative volunteers.

ASPIRE I and II were prospective, 3-way sequential crossover studies in healthy volunteers to compare the safety and pharmacokinetics of saquinavir/ritonavir (SQV/RTV) with saquinavir/atazanavir (SQV/ATV) administered either once daily (QD, ASPIRE I) or twice daily (BID, ASPIRE II). Treatments were separated by 10 days, and pharmacokinetic analyses were performed on days 11, 32, and 53. SQV pharmacokinetics were significantly higher when dosed with RTV compared to ATV (P < .

Disease progression in HIV-infected patients treated with stavudine vs. zidovudine.

Background And Objectives: This prospective, observational study compared disease progression and death in HIV-1 patients treated with stavudine vs. zidovudine in the Collaborations in HIV Outcomes Research/U.S.

Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial.

Background: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1.

Objective: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy.

Design: Randomized, double-blind, placebo-controlled study through 24 weeks.

The role of pharmacological enhancement in protease inhibitor-based highly active antiretroviral therapy.

Having changed the landscape in the treatment of HIV infection, the functional efficacy of current protease inhibitors (PIs) remains limited by their pharmacokinetic and pharmacodynamic profiles. Complex metabolism by the cytochrome P450 system (particularly the 3A4 isoenzyme), action of membrane drug transporter elements (such as P-glycoprotein and multi-drug resistance-associated proteins) and activation of the nuclear receptor steroid xenobiotic receptor may alter exposures and compromise the antiretroviral activity of these drugs. These factors, as well as inadequate adherence, can facilitate the emergence of PI resistance and lead to regimen failure.

Young HIV-infected adults are at greater risk for medication nonadherence.

This study sought to estimate rates of adherence to nucleoside reverse transcriptase inhibitors (NRTIs) during the first year of administration in the California Medicaid (Medi-Cal) population. A retrospective analysis of pharmacy claims data regarding NRTI prescription refills was employed to estimate adherence and persistence with therapy throughout 1 year in treatment-naive individuals. Adherence was defined as the proportion of days on which drugs were taken during the first 365 days of therapy, and persistence was assessed according to whether prescriptions were refilled over time within a tolerable threshold (60 days).