Tenofovir and Emtricitabine Resistance among Antiretroviral-Naive Patients in the Canadian Observational Cohort Collaboration: Implications for PrEP. Issue 3 (April 2019)

• Record Type: Journal Article
• Other Names: Younger Jaime non-byline-author.; Raboud Janet non-byline-author.; Szadkowski Leah non-byline-author.; Harrigan Richard non-byline-author.; Walmsley Sharon non-byline-author.; Bayoumi Ahmed M non-byline-author.; Klein Marina B non-byline-author.; Cooper Curtis non-byline-author.; Burchell Ann N non-byline-author.; Loutfy Mona non-byline-author.; Hull Mark non-byline-author.; Wong Alex non-byline-author.; Thomas Rejean non-byline-author.; Hogg Robert non-byline-author.; Montaner Julio non-byline-author.; Tsoukas Chris non-byline-author.; Antoniou Tony non-byline-author.
• Is Part Of: Antiviral therapy. Volume 24:Issue 3(2019)
• Page Start: 211
• Page End: 220
• Publication Date: 2019-04
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3302
• Languages: English
• ISSNs: 1359-6535

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-naive 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 6, 622 antiretroviral-naive participants initiating therapy, of whom 5, 428 (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 5 years following treatment initiation was 0.0070 (95% CI 0.0046, 0.0095) and 0.033 (95% CI 0.028, 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, 6.15) and emtricitabine (HR 2.27; 95% CI 1.64, 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4 + T-cell count below 200 cells/mm 3 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-naive patients in routine clinical care.