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Antivir Ther. 2019 Mar 15. doi: 10.3851/IMP3302. [Epub ahead of print]

Tenofovir and emtricitabine resistance among antiretroviral-naive patients in the Canadian Observational Cohort Collaboration: implications for PrEP.

Author information

1
Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
2
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
3
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
4
Department of Medicine, University of Toronto, Toronto, ON, Canada.
5
Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
6
CIHR Canadian HIV Trials Network, Vancouver, BC.
7
Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
8
Department of Medicine, McGill University Health Centre Research Institute, Montréal, QC, Canada.
9
Ottawa Hospital Research Institute, Ottawa, ON, Canada.
10
Department of Family and Community Medicine, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada.
11
Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
12
Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada.
13
Maple Leaf Medical Clinic, Toronto, ON, Canada.
14
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
15
Division of Infectious Diseases, Department of Medicine, University of Saskatchewan, Regina, SK, Canada.
16
Clinique Médicale L'Actuel, Montreal, QC, Canada.
17
Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada.
18
Faculty of Medicine, McGill University Health Centre, Montréal, QC, Canada.
19
Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Abstract

BACKGROUND:

The real-world effectiveness of pre-exposure prophylaxis (PrEP) may be influenced by circulating HIV strains resistant to either tenofovir or emtricitabine. Yet, few studies have examined rates of resistance to these drugs in clinical settings.

METHODS:

We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort collaboration who initiated antiretroviral therapy between 2006 and 2014. In separate analyses, we determined the prevalence of pretherapy resistance and cumulative incidence of follow-up resistance to tenofovir and emtricitabine. We used multivariable proportional hazards models to examine associations between baseline variables and the development of resistance.

RESULTS:

We studied 6622 antiretroviral naïve participants initiating therapy, of whom 5428 (82.0%) had a baseline resistance test. Baseline resistance to tenofovir and emtricitabine was observed in 83 (1.5%) and 21 (0.4%) patients, respectively. Among patients without baseline resistance, the cumulative incidence of resistance to tenofovir and emtricitabine five years following treatment initiation was 0.0070 [95% confidence interval (CI) 0.0046 to 0.0095] and 0.033 (95% CI 0.028 to 0.038), respectively. Following multivariable analysis, a baseline viral load ≥ 100,000 copies/mL was associated with emergence of tenofovir [hazard ratio (HR) 2.88; 95% CI 1.35 to 6.15] and emtricitabine (HR 2.27; 95% CI 1.64 to 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4 count below 200 cells/mm3 were also associated with resistance to each drug.

CONCLUSIONS:

We observed a low prevalence of baseline resistance and a low incidence of emergence of resistance to tenofovir and emtricitabine among antiretroviral naïve patients in routine clinical care.

PMID:
30873953
DOI:
10.3851/IMP3302

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