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

Keith W. Crawford, John Spritzler, Robert C. Kalayjian, Teresa Parsons, Alan Landay, Richard B Pollard, Vicki Stocker, Michael M. Lederman, Charles Flexner

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 200mg qd, and stavudine 40mg 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.

Original languageEnglish (US)
Pages (from-to)635-643
Number of pages9
JournalAIDS Research and Human Retroviruses
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Lopinavir
HIV Protease Inhibitors
HIV
Pharmacokinetics
Population
Anti-Retroviral Agents
Stavudine
Ritonavir
Highly Active Antiretroviral Therapy
Self Report
Age Groups
Safety

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Crawford, K. W., Spritzler, J., Kalayjian, R. C., Parsons, T., Landay, A., Pollard, R. B., ... Flexner, C. (2010). Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. AIDS Research and Human Retroviruses, 26(6), 635-643. https://doi.org/10.1089/aid.2009.0154

Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. / Crawford, Keith W.; Spritzler, John; Kalayjian, Robert C.; Parsons, Teresa; Landay, Alan; Pollard, Richard B; Stocker, Vicki; Lederman, Michael M.; Flexner, Charles.

In: AIDS Research and Human Retroviruses, Vol. 26, No. 6, 01.06.2010, p. 635-643.

Research output: Contribution to journalArticle

Crawford, KW, Spritzler, J, Kalayjian, RC, Parsons, T, Landay, A, Pollard, RB, Stocker, V, Lederman, MM & Flexner, C 2010, 'Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir', AIDS Research and Human Retroviruses, vol. 26, no. 6, pp. 635-643. https://doi.org/10.1089/aid.2009.0154
Crawford, Keith W. ; Spritzler, John ; Kalayjian, Robert C. ; Parsons, Teresa ; Landay, Alan ; Pollard, Richard B ; Stocker, Vicki ; Lederman, Michael M. ; Flexner, Charles. / Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. In: AIDS Research and Human Retroviruses. 2010 ; Vol. 26, No. 6. pp. 635-643.
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