Intracellular and plasma pharmacokinetics of nelfinavir and M8 in HIV-infected patients: relationship with P-glycoprotein expression.

One of the targets of antiretroviral therapy is within cells infected with HIV. In order to improve therapeutic efficacy, it is therefore important that the intracellular pharmacokinetics of drugs, such as nelfinavir mesylate and its active metabolite M8, are studied in addition to plasma pharmacokinetics. Previously, the intracellular accumulation of protease inhibitors has been reported in vivo, displaying the following hierarchy: nelfinavir > saquinavir > ritonavir > indinavir.

Raised viral load in patients with viral suppression on highly active antiretroviral therapy: transient increase or treatment failure?

Objective: To assess the occurrence of viral load greater than 50 copies/ml in patients on highly active antiretroviral therapy (HAART) having achieved less than 50 copies/ml and the chance of whether a viral load greater than 50 copies/ml would lead to a sustained and increasing viral load.

Design: A cohort of 553 patients on HAART with viral loads of less than 50 copies/ml were followed.

Results: Over a median of 56 weeks 35% of patients experienced a transient increase and 8% virological failure (two consecutive viral loads of > 400 copies/ml).