Objective: To assess the association between antiretroviral adherence and the development of class-specific antiretroviral medication resistance.
Design and methods: Literature and conference abstract review of studies assessing the association between adherence to antiretroviral therapy and the development of antiretroviral medication resistance.
Results: Factors that determine class-specific adherence–resistance relationships include antiretroviral regimen potency, viral fitness or, more specifically, the interplay between the fold-change in resistance and fold-change in fitness caused by drug resistance mutations, and the genetic barrier to antiretroviral resistance. During multidrug therapy, differential drug exposure increases the likelihood of developing resistance. In addition, antiretroviral medications with higher potency and higher genetic barriers to resistance decrease the incidence of resistance for companion antiretroviral medications at all adherence levels.
Conclusion: Knowledge of class-specific adherence–resistance relationships may help clinicians and patients tailor therapy to match individual patterns of adherence in order to minimize the development of resistance at failure. In addition, this information may guide the selection of optimal drug combinations and regimen sequences to improve the durability of antiretroviral therapy.
aDenver Public Health, Denver, USA
bInstitute for Health Research, Kaiser Permanente Colorado, USA
cDepartment of Medicine, USA
dDepartment of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA
eMassachusetts General Hospital, Harvard Medical School, Harvard Initiative for Global Health, Boston, Massachusetts, USA.
Received 11 December, 2008
Revised 6 March, 2009
Accepted 15 March, 2009
Correspondence to Edward M. Gardner, MD, Denver Public Health, 605 Bannock Street, Denver, CO 80204, USA. Tel: +1 303 602 8740; fax: +1 303 602 8739; e-mail: email@example.com