Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

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

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

OBJECTIVES: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. DESIGN: A secondary analysis of prospective clinical trial data. METHODS: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. RESULTS: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. CONCLUSION: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalAIDS
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Reverse Transcriptase Inhibitors
Protease Inhibitors
Retroviridae
HIV-1
Acquired Immunodeficiency Syndrome
Therapeutics
Regression Analysis
Demography
Clinical Trials
HIV
RNA
Research

Keywords

  • Adherence
  • Antiretroviral resistance
  • Differential adherence
  • HIV
  • Virological failure

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance. / Gardner, Edward M.; Sharma, Shweta; Peng, Grace; Hullsiek, Katherine Huppler; Burman, William J.; MacArthur, Rodger David; Chesney, Margaret; Telzak, Edward E.; Friedland, Gerald; Mannheimer, Sharon B.

In: AIDS, Vol. 22, No. 1, 01.01.2008, p. 75-82.

Research output: Contribution to journalArticle

Gardner, EM, Sharma, S, Peng, G, Hullsiek, KH, Burman, WJ, MacArthur, RD, Chesney, M, Telzak, EE, Friedland, G & Mannheimer, SB 2008, 'Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance', AIDS, vol. 22, no. 1, pp. 75-82. https://doi.org/10.1097/QAD.0b013e3282f366ff
Gardner, Edward M. ; Sharma, Shweta ; Peng, Grace ; Hullsiek, Katherine Huppler ; Burman, William J. ; MacArthur, Rodger David ; Chesney, Margaret ; Telzak, Edward E. ; Friedland, Gerald ; Mannheimer, Sharon B. / Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance. In: AIDS. 2008 ; Vol. 22, No. 1. pp. 75-82.
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T1 - Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

AU - Gardner, Edward M.

AU - Sharma, Shweta

AU - Peng, Grace

AU - Hullsiek, Katherine Huppler

AU - Burman, William J.

AU - MacArthur, Rodger David

AU - Chesney, Margaret

AU - Telzak, Edward E.

AU - Friedland, Gerald

AU - Mannheimer, Sharon B.

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N2 - OBJECTIVES: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. DESIGN: A secondary analysis of prospective clinical trial data. METHODS: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. RESULTS: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. CONCLUSION: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

AB - OBJECTIVES: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. DESIGN: A secondary analysis of prospective clinical trial data. METHODS: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. RESULTS: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. CONCLUSION: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

KW - Adherence

KW - Antiretroviral resistance

KW - Differential adherence

KW - HIV

KW - Virological failure

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