Concentration-controlled compared with conventional antiretroviral therapy for HIV infection

Courtney V. Fletcher, Peter L. Anderson, Thomas N. Kakuda, Timothy W. Schacker, Keith Henry, Cynthia R. Gross, Richard C. Brundage

Research output: Contribution to journalArticlepeer-review

142 Scopus citations


Objectives: To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy. Design: A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States. Patients: Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml. Interventions: Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values. Main outcome measures: The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms. Results: Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms. Conclusion: Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.

Original languageEnglish (US)
Pages (from-to)551-560
Number of pages10
Issue number4
StatePublished - Mar 8 2002
Externally publishedYes


  • Antiretroviral therapy
  • Combination therapy
  • Drug concentrations
  • Pharmacokinetics
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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