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


METHODS
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.


CONCLUSIONS
Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.
Gardner
Edward M
EM
Denver Public Health, Denver, Colorado 80204, USA. edward.gardner@dhha.org
Sharma
Shweta
S
Peng
Grace
G
Hullsiek
Katherine Huppler
KH
Burman
William J
WJ
Macarthur
Rodger D
RD
Chesney
Margaret
M
Telzak
Edward E
EE
Friedland
Gerald
G
Mannheimer
Sharon B
SB
D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010349:Patient Compliance; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors