Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial

Edward M. Gardner, Katherine H. Hullsiek, Edward E. Telzak, Shweta Sharma, Grace Peng, William J. Burman, Rodger David MacArthur, Margaret Chesney, Gerald Friedland, Sharon B. Mannheimer

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objective: To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance. Design: Secondary analysis of prospective clinical trial data. Methods: Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis. Results: Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9-1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1-1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure. Conclusion: Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.

Original languageEnglish (US)
Pages (from-to)395-403
Number of pages9
JournalAIDS
Volume24
Issue number3
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Reverse Transcriptase Inhibitors
Medication Adherence
Protease Inhibitors
Clinical Trials
Confidence Intervals
Retroviridae
Nucleosides
Self Report
Acquired Immunodeficiency Syndrome
Regression Analysis
HIV
RNA
Therapeutics
Research

Keywords

  • Adherence
  • Antiretroviral resistance
  • Antiretroviral therapy
  • HIV
  • Virological failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Gardner, E. M., Hullsiek, K. H., Telzak, E. E., Sharma, S., Peng, G., Burman, W. J., ... Mannheimer, S. B. (2010). Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial. AIDS, 24(3), 395-403. https://doi.org/10.1097/QAD.0b013e328335cd8a

Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial. / Gardner, Edward M.; Hullsiek, Katherine H.; Telzak, Edward E.; Sharma, Shweta; Peng, Grace; Burman, William J.; MacArthur, Rodger David; Chesney, Margaret; Friedland, Gerald; Mannheimer, Sharon B.

In: AIDS, Vol. 24, No. 3, 01.01.2010, p. 395-403.

Research output: Contribution to journalArticle

Gardner, EM, Hullsiek, KH, Telzak, EE, Sharma, S, Peng, G, Burman, WJ, MacArthur, RD, Chesney, M, Friedland, G & Mannheimer, SB 2010, 'Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial', AIDS, vol. 24, no. 3, pp. 395-403. https://doi.org/10.1097/QAD.0b013e328335cd8a
Gardner EM, Hullsiek KH, Telzak EE, Sharma S, Peng G, Burman WJ et al. Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial. AIDS. 2010 Jan 1;24(3):395-403. https://doi.org/10.1097/QAD.0b013e328335cd8a
Gardner, Edward M. ; Hullsiek, Katherine H. ; Telzak, Edward E. ; Sharma, Shweta ; Peng, Grace ; Burman, William J. ; MacArthur, Rodger David ; Chesney, Margaret ; Friedland, Gerald ; Mannheimer, Sharon B. / Antiretroviral medication adherence and class-specific resistance in a large prospective clinical trial. In: AIDS. 2010 ; Vol. 24, No. 3. pp. 395-403.
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abstract = "Objective: To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance. Design: Secondary analysis of prospective clinical trial data. Methods: Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis. Results: Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30{\%}) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28{\%}) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95{\%} confidence interval (CI) 0.9-1.4 per 10{\%} lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95{\%} CI 1.1-1.3 per 10{\%} lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure. Conclusion: Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.",
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AU - Peng, Grace

AU - Burman, William J.

AU - MacArthur, Rodger David

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KW - Antiretroviral therapy

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