Rapid estimated glomerular filtration rate (eGFR) decline is a risk factor for cardiovascular events in diabetics and for mortality in the general population. In HIV-positive people, tenofovir (TDF) and atazanavir (ATV) have been associated with rapid eGFR decline. We analysed risk factors for, and mortality associated with, rapid eGFR decline in subjects receiving TDF and/or ATV.
Individuals in UK CHIC with a first episode of either TDF or ATV exposure since 1/1/2000 with ≥1 year exposure and ≥1 creatinine value (excluding first 3 months after TDF/ATV start) were considered for analysis. Despite overlap, periods of TDF and ATV exposure were analysed separately. eGFR slopes were generated for each group using mixed effects models adjusted for age, ethnicity and sex; individuals with rapid eGFR decline (>3mL/min/1.73m²/year) were identified. Demographic and HIV factors associated with rapid eGFR decline for those on TDF and ATV were analysed using logistic regression, and factors associated with all-cause mortality using Poisson regression.
16172 individuals commenced TDF (mean age 38 years, 73% white, 79% male, mean eGFR at TDF start 82 mL/min/1.73m², 21% co-administered with ATV) and 4162 commenced ATV (mean age 37 years, 68% white, 72% male, mean eGFR at ATV start 80, 81% co-administered with TDF). Adjusted eGFR slopes (95% CI) for TDF and ATV were -0.26 (-0.33, -0.19) and -0.61 (-0.79, -0.43) respectively; 15.8% of those on TDF and 21.7% of those on ATV experienced rapid eGFR decline. In adjusted analyses, rapid eGFR decline was associated with black ethnicity, lower baseline eGFR and shorter TDF/ATV exposure (Table 1). In addition, younger age, AIDS and co-exposure to ATV/lopinavir (LPV) in the TDF group and female sex and TDF exposure in the ATV group were associated with rapid decline. During a mean (SD) follow up of 8.0 (4.8) years, 573 died. After adjustment for age, sex, ethnicity, nadir CD4, hepatitis status, baseline eGFR and ART regimen, rapid eGFR decline remained associated with all-cause mortality (aHR [95% CI] 1.56 [1.27, 1.92] and 1.83 [1.31, 2.56] for TDF and ATV respectively, p<0.001). Similar results were obtained when rapid eGFR decline was defined as >5 mL/min/1.73m²/year.
Rapid eGFR decline was observed in a substantial proportion of those who received TDF or ATV and identified a subset of patients at increased risk of death. Black ethnicity, lower baseline eGFR, TDF/ATV and TDF/LPV co-exposure were associated with rapid eGFR decline.