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Antiretroviral Risk Factors for Kidney Disease in EuroSIDA:
Tenofovir Is Not Alone
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Cumulative exposure to tenofovir, atazanavir, lopinavir, or indinavir, plus non-AIDS cancer and hepatitis C virus coinfection, each ballooned the risk of chronic kidney disease (CKD) in a large EuroSIDA analysis [1]. CKD prevalence was consistent with other reports involving HIV-infected people.
Ole Kirk and EuroSIDA colleagues foraged for CKD risk factors in 6843 cohort members, 85.5% of them white, 25% female, 43% gay men, 23% positive for HCV antibody, and 90% with antiretroviral experience. While 22% had arterial hypertension, 5% had diabetes mellitus. Median age stood at 42.8 years (interquartile range [IQR] 37.5 to 50.0) and median CD4 count at 450 (IQR 305 to 638).
The investigators defined CKD as a confirmed estimated glomerular filtration rate (eGFR) at or below 60 mL/min/1.73 m(2) if above that level at baseline or a 25% drop in eGFR if initially below the 60-mL cutoff. They calculated antiretroviral exposure as cumulative exposure by month modeled as a time-updated variable.
During a median 3.7 years of follow-up (IQR 2.8 to 5.7), CKD developed in 225 people (3.3%) for an incidence of 1.1 per 100 person-years. Of the 203 people (90%) with a baseline eGFR above 60, 105 (74% of 203) saw their eGFR fall by more than 10 mL/min/1.7 m(2).
A multivariate model to calculate the impact of antiretroviral exposure on CKD risk considered age, gender, baseline eGFR, AIDS at baseline or during follow-up, use of nephrotoxic drugs, current CD4 count, viral load, any cardiovascular event, arterial hypertension, diabetes, HCV antibody status, and non-AIDS malignancies. Four antiretrovirals independently raised the risk of CKD:
· Tenofovir: incidence rate ratio (IRR) per year 1.16, 95% confidence interval [CI] 1.06 to 1.25, P < 0.0001
· Indinavir: IRR per year 1.12, 95% CI 1.06 to 1.18, P < 0.0001
· Atazanavir: IRR per year 1.21, 95% CI 1.09 to 1.34, P = 0.0003
· Lopinavir/ritonavir: IRR per year 1.08, 95% CI 1.01 to 1.16, P = 0.030
These risks did not change appreciably when Kirk censored the analyses from the time of starting atazanavir, tenofovir, or a ritonavir-boosted PI.
Stopping tenofovir during follow-up did slowly trim the risk of CKD. Within the first year of stopping, the IRR for tenofovir use stood at 4.05 (95% CI 2.51 to 6.53) compared with people who never took tenofovir. After that, the risk dropped into nonsignificance (IRR 1.12, 95% CI 0.63 to 1.99). CKD risk among people stopping atazanavir or lopinavir/ritonavir rapidly looked similar to the risk in people who never took those drugs.
AIDS, non-AIDS malignancies, and coinfection with HCV also independently raised the risk of CKD, but Kirk did not detail IRRs for those risk factors. He noted that follow-up was too brief to exclude the possibility of associations with more recently licensed antiretrovirals, including darunavir, tipranavir, etravirine, maraviroc, and raltegravir.
Reference
1. Kirk O, Mocroft A, Reiss P, et al. Chronic kidney disease and exposure to ART in a large cohort with long-term follow-up: the EuroSIDA study. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 107LB.
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