6th IAS Conference On HIV Pathogenesis, Treatment and Prevention

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Progression to impaired estimated glomerular filtration rate (eGFR) between antiretroviral therapy regimens in the Canadian Observational Cohort (CANOC) collaboration

S.R. Hosein1,2, K. Johns3, K. Chan4, J. Raboud5,6, M. Harris3,4, D. Milan4, G. Bondy7, A.M. Cescon4, C. Cooper8, M.B. Klein9,10, M.R. Loutfy11,12,13, N. Machouf14, J.S. Montaner3,4, C. Tsoukas10, R.S. Hogg4,15, A. Rachlis16, CANOC Collaboration

1CATIE, Toronto, Canada, 2Canadian Observational Cohort (CANOC) collaboration, Vancouver, Canada, 3University of British Columbia, Faculty of Medicine, Vancouver, Canada, 4BC Centre for Excellence in HIV/AIDS, Vancouver, Canada, 5University Health Network, Division of Infectious Diseases, Toronto, Canada, 6University of Toronto, Dalla Lana School of Public Health, Toronto, Canada, 7University of British Columbia, Department of Medicine and Pathology, Vancouver, Canada, 8University of Ottawa, The Ottawa Hospital Division of Infectious Diseases, Ottawa, Canada, 9McGill University Health Centre, The Montreal Chest Institute, Montreal, Canada, 10McGill University, Faculty of Medicine, Montreal, Canada, 11Women's College Hospital, Women's College Research Institute, Toronto, Canada, 12Maple Leaf Medical Clinic, Toronto, Canada, 13University of Toronto, Faculty of Medicine, Toronto, Canada, 14Clinique Medicale l'Actuel, Montreal, Canada, 15Simon Fraser University, Faculty of Health Sciences, Burnaby, Canada, 16University of Toronto, Department of Medicine, Division of Infectious Diseases, Toronto, Canada

Background: Although potent antiretroviral therapy (ART) can significantly extend survival, concerns remain about long-term safety. Renal safety is an emerging issue in the treatment of chronic HIV infection and eGFR is an important clinical tool for assessing renal function. This study investigates whether use of atazanavir or lopinavir correlates to progression to impaired eGFR among patients on NRTI backbone containing either tenofovir (TDF) or abacavir (ABC).
Methods: Treatment-naïve HIV-1-infected participants with initial ART regimens containing TDF or ABC were prospectively followed since 2000 across Canada. Regular assessments of viral load, CD4+ cell count, co-infections, creatinine, and lipid parameters were conducted. MDRD equations were used to calculate eGFR. Cox regression analysis was used for time to impaired eGFR (defined as < 60 mL/min).
Results: A total of 965 patients were included in this analysis (87% male, 13% female), median age 39 years (IQR 33-45), 14% known IDU, 18% hepatitis C positive, median CD4 219 cells/mm3 (IQR 137-290), median VL 4.8 log10 copies/ml (IQR 4.3-5.0). Baseline NRTI use included 283 on ABC and 682 on TDF; initial third agents included 384 on atazanavir, 192 on lopinavir, and 389 on non-PI. In a multivariable proportional hazards model adjusting for province, baseline CD4, baseline VL, age, year therapy started, baseline eGFR and rate of eGFR testing, TDF use was not associated with increase risk of impaired eGFR (aHR 1.16, 95% CI 0.94-1.43, p=.177) compared to ABC use. Both lopinavir (aHR 1.32, 95% CI 1.04-1.69, p=.024) and atazanavir (aHR 1.46, 95% CI 1.18-1.81, p< .001) were associated with impaired eGFR relative to non-PI use.
Conclusion: Results from this cohort suggest that treatment-naïve HIV-positive patients who are given PI-based regimens, particularly atazanavir, appear to be at increased risk for mild-to-moderate renal toxicity. We plan further analyses to explore this finding.

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