Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy.
OBJECTIVE
The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada.


METHODS
All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations.


RESULTS
Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001).


CONCLUSIONS
High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
Harrigan
P Richard
PR
British Columbia Centre for Excellence in HIV/AIDS, and Department of Medicine, University of British Columbia, Vancouver, Canada. lab@hivnet.ubc.ca
Hogg
Robert S
RS
Dong
Winnie W Y
WW
Yip
Benita
B
Wynhoven
Brian
B
Woodward
Justin
J
Brumme
Chanson J
CJ
Brumme
Zabrina L
ZL
Mo
Theresa
T
Alexander
Chris S
CS
Montaner
Julio S G
JS
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001955:British Columbia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015994:Incidence; D015999:Multivariate Analysis; D009154:Mutation; D010349:Patient Compliance; D019562:Viral Load
D054303:HIV Reverse Transcriptase; D016333:HIV Protease