Critical issues in therapeutic drug monitoring of antiretroviral drugs.

The interest in therapeutic drug monitoring (TDM) of antiretroviral drugs is growing rapidly. For the protease inhibitors, and to a lesser extent for the non-nucleoside reverse transcriptase inhibitors, relationships between plasma drug concentrations and their efficacy and toxicity have been identified. Furthermore, the pharmacokinetics of especially the protease inhibitors vary widely between patients, suggesting a role for TDM to individualize antiretroviral therapy.

Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.

Objectives: To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR).

Methods: Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment.

Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile.

Background: Protease inhibitor-containing antiretroviral therapy for the treatment of HIV-1 infection is associated with elevated triglyceride and low-density lipoprotein (LDL)-cholesterol levels which may expose patients to an increased risk of coronary artery disease (CAD). We report the lipid and lipoprotein profiles of a representative subset of treatment-naive patients included in the Atlantic Study. This study compares patients treated with stavudine and didanosine plus the random addition of either the non-nucleoside reverse transcriptase inhibitor nevirapine (NVP), the protease inhibitor indinavir or the nucleoside reverse transcriptase inhibitor lamivudine.

Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection.

Background: Changes in body fat distribution are an adverse effect of therapy with HIV protease inhibitors (PI). It has been suggested that nucleoside analogue reverse transcriptase inhibitors (NRTI) may also contribute to this so-called lipodystrophy syndrome, but the relative contribution of the two drug classes is unclear as they are usually administered concomitantly.

Method: The occurrence of lipodystrophy, as reported by physicians using no standardized criteria, was followed in patients randomly assigned to treatment with either a PI alone or a PI combined with an NRTI.