Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir.

TitleAge-related changes in plasma concentrations of the HIV protease inhibitor lopinavir.
Publication TypeJournal Article
Year of Publication2010
AuthorsCrawford KW, Spritzler J, Kalayjian RC, Parsons T, Landay A, Pollard R, Stocker V, Lederman MM, Flexner C
Corporate AuthorsAIDS Clinical Trials Protocol 5015 Team
JournalAIDS Res Hum Retroviruses
Date Published2010 Jun
KeywordsAdolescent, Adult, Age Factors, Aged, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Female, HIV Infections, HIV Protease Inhibitors, Humans, Lopinavir, Male, Middle Aged, Plasma, Pyrimidinones, Young Adult

The advent of highly active antiretroviral therapy in the treatment of HIV disease has substantially extended the lifespan of individuals infected with HIV resulting in a growing population of older HIV-infected individuals. The efficacy and safety of antiretroviral agents in the population are important concerns. There have been relatively few studies assessing antiretroviral pharmacokinetics in older patients. Thirty-seven subjects aged 18-30 years and 40 subjects aged 45-79 years, naive to antiretroviral therapy, received lopinavir/ritonavir (400/100) bid, emtricitibine 200 mg qd, and stavudine 40 mg bid. Trough lopinavir concentrations were available for 44 subjects, collected at 24, 36, and 96 weeks. At week 24, older age was associated with higher lopinavir trough concentrations, and a trend was observed toward older age being associated with higher lopinavir trough concentrations when all time points were evaluated. In the young cohort, among subjects with two or more measurements, there was a trend toward increasing intrasubject trough lopinavir concentrations over time. Using a nonlinear, mixed-effects population pharmacokinetic model, age was negatively associated with lopinavir clearance after adjusting for adherence. Adherence was assessed by patient self-reports; older patients missed fewer doses than younger patients (p = 0.02). No difference in grade 3-4 toxicities was observed between the two age group. Older patients have higher trough lopinavir concentrations and likely decreased lopinavir clearance. Age-related changes in the pharmacokinetics of antiretroviral drugs may be of increasing importance as the HIV-infected population ages and as older individuals comprise an increasing proportion of new diagnoses.

Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID20560793
PubMed Central IDPMC2932550
Grant ListAI068634 / AI / NIAID NIH HHS / United States
AI069465 / AI / NIAID NIH HHS / United States
U01 AI68636 / AI / NIAID NIH HHS / United States