Antiretroviral Medication Adherence and the Development of Class-specific Antiretroviral Resistance

Overview

Journal AIDS

Specialty Infectious Diseases

Date 2009 Apr 22

PMID 19381075

Citations 74

Authors

Edward M Gardner

William J Burman

John F Steiner

Peter L Anderson

David R Bangsberg

Affiliations

Soon will be listed here.

Abstract

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.

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References

Elliott J, Lynen L, Calmy A, De Luca A, Shafer R, Zolfo M . Rational use of antiretroviral therapy in low-income and middle-income countries: optimizing regimen sequencing and switching. AIDS. 2008; 22(16):2053-67. DOI: 10.1097/QAD.0b013e328309520d. View

Palella Jr F, Delaney K, Moorman A, Loveless M, Fuhrer J, Satten G . Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998; 338(13):853-60. DOI: 10.1056/NEJM199803263381301. View

Parienti J, Massari V, Descamps D, Vabret A, Bouvet E, Larouze B . Predictors of virologic failure and resistance in HIV-infected patients treated with nevirapine- or efavirenz-based antiretroviral therapy. Clin Infect Dis. 2004; 38(9):1311-6. DOI: 10.1086/383572. View

Rajabiun S, Mallinson R, McCoy K, Coleman S, Drainoni M, Rebholz C . "Getting me back on track": the role of outreach interventions in engaging and retaining people living with HIV/AIDS in medical care. AIDS Patient Care STDS. 2007; 21 Suppl 1:S20-9. DOI: 10.1089/apc.2007.9990. View

Parienti J, Das-Douglas M, Massari V, Guzman D, Deeks S, Verdon R . Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PLoS One. 2008; 3(7):e2783. PMC: 2467488. DOI: 10.1371/journal.pone.0002783. View

Louie M, Hogan C, Di Mascio M, Hurley A, Simon V, Rooney J . Determining the relative efficacy of highly active antiretroviral therapy. J Infect Dis. 2003; 187(6):896-900. DOI: 10.1086/368164. View

Bangsberg D, Charlebois E, Grant R, Holodniy M, Deeks S, Perry S . High levels of adherence do not prevent accumulation of HIV drug resistance mutations. AIDS. 2003; 17(13):1925-32. DOI: 10.1097/00002030-200309050-00011. View

Gardner E, Burman W, Maravi M, Davidson A . Selective drug taking during combination antiretroviral therapy in an unselected clinic population. J Acquir Immune Defic Syndr. 2005; 40(3):294-300. DOI: 10.1097/01.qai.0000182229.84182.06. View

Coffin J . HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995; 267(5197):483-9. DOI: 10.1126/science.7824947. View

10.

Beerenwinkel N, Daumer M, Sing T, Rahnenfuhrer J, Lengauer T, Selbig J . Estimating HIV evolutionary pathways and the genetic barrier to drug resistance. J Infect Dis. 2005; 191(11):1953-60. DOI: 10.1086/430005. View

11.

Bangsberg D . Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression. Clin Infect Dis. 2006; 43(7):939-41. DOI: 10.1086/507526. View

12.

Walmsley S, Bernstein B, King M, Arribas J, Beall G, Ruane P . Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N Engl J Med. 2002; 346(26):2039-46. DOI: 10.1056/NEJMoa012354. View

13.

Saravolatz L, Winslow D, Collins G, Hodges J, Pettinelli C, Stein D . Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for.... N Engl J Med. 1996; 335(15):1099-106. DOI: 10.1056/NEJM199610103351503. View

14.

Bangsberg D, Kroetz D, Deeks S . Adherence-resistance relationships to combination HIV antiretroviral therapy. Curr HIV/AIDS Rep. 2007; 4(2):65-72. DOI: 10.1007/s11904-007-0010-0. View

15.

Schackman B, Gebo K, Walensky R, Losina E, Muccio T, Sax P . The lifetime cost of current human immunodeficiency virus care in the United States. Med Care. 2006; 44(11):990-7. DOI: 10.1097/01.mlr.0000228021.89490.2a. View

16.

Mansky L . The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology. 1996; 222(2):391-400. DOI: 10.1006/viro.1996.0436. View

17.

Deeks S . Treatment of antiretroviral-drug-resistant HIV-1 infection. Lancet. 2003; 362(9400):2002-11. DOI: 10.1016/S0140-6736(03)15022-2. View

18.

Preston B, Poiesz B, Loeb L . Fidelity of HIV-1 reverse transcriptase. Science. 1988; 242(4882):1168-71. DOI: 10.1126/science.2460924. View

19.

Harrigan P, Hogg R, Dong W, Yip B, Wynhoven B, Woodward J . Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. J Infect Dis. 2005; 191(3):339-47. DOI: 10.1086/427192. View

20.

Quinn T . HIV epidemiology and the effects of antiviral therapy on long-term consequences. AIDS. 2008; 22 Suppl 3:S7-12. PMC: 2753265. DOI: 10.1097/01.aids.0000327510.68503.e8. View