Background: Combination antiretroviral therapy (cART) has reduced mortality from AIDS-related illnesses and chronic comorbidities have become prevalent among HIV-infected patients. We examined the association between hepatitis C virus (HCV) co-infection and chronic kidney disease (CKD) among patients initiating modern antiretroviral therapy. Methods: Data were obtained from the Canadian HIV Observational Cohort for individuals initiating cART from 2000 to 2012. Incident CKD was defined as two consecutive serum creatinine-based estimated glomerular filtration (eGFR) measurements= 3 months apart. CKD incidence rates after cART initiation were compared between HCV co-infected and HIV mono-infected patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. Results: We included 2595 HIV-infected patients with eGFR >60 mL/min/1.73 m(2) at cART initiation, of which 19% were HCV co-infected. One hundred and fifty patients developed CKD during 10,903 person-years of follow-up (PYFU). The CKD incidence rate was higher among co-infected than HIV mono-infected patients (26.0 per 1000 PYFU vs. 10.7 per 1000 PYFU). After adjusting for demographics, virologic parameters and traditional CKD risk factors, HCV co-infection was associated with a significantly shorter time to incident CKD (HR 1.97; 95% CI: 1.33, 2.90). Additional factors associated with incident CKD were female sex, increasing age after 40 years, lower baseline eGFR below 100 mL/min/1.73 m(2), increasing HIV viral load and cumulative exposure to tenofovir and lopinavir. Conclusions: HCV co-infection was associated with an increased risk of incident CKD among HIV-infected patients initiating cART. HCV-HIV co-infected patients should be monitored for kidney disease and may benefit from available HCV treatments.