Higher CKD Risk in HIV With Combination Tenofovir, Boosted Protease Inhibitor

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hand holding two pills
In patients living with HIV receiving TDF with a ritonavir-boosted protease inhibitor, the risk of CKD may be increased.

The risk of chronic kidney disease (CKD) may be increased in patients living with HIV receiving tenofovir (TDF) with a ritonavir-boosted protease inhibitor compared to those who receive TDF with a non-nucleosidic reverse transcriptase inhibitor (NNRTI), according to new research published in PLOS One.

To investigate whether certain antiretroviral (ART) combinations were associated with a greater risk of CKD, study authors evaluated a large prospective cohort (N = 6301) which included HIV patients who had initiated their first ART regimen after January 1, 2004, had at least 1 serum creatinine measurement within 6 months pre-ART regimen (study entry), and had at least 2 measurements after study entry. A CKD event was defined as an eGFR <60mL/min/1.73m2 measured 3 months apart. The time to event was the time between ART initiation and the first eGFR <60mL/min/1.73m2

The regimens were divided into 5 combinations: TDF + ritonavir-boosted protease inhibitor, TDF + NNRTI, a ritonavir-boosted protease inhibitor without TDF, an NNRTI without TDF, and any other combination with or without TDF.

CKD occurrence was seen in 3.4% of patients, corresponding to an incidence of 9.6 (95% CI, 8.3–10.9) cases per 1000 person-years. Of these, 41% had developed CKD while on their initial ART regimen with an incidence of 6.9 cases per 1000 person-years. 

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The data showed a higher risk of CKD associated with an initial regimen of TDF with a ritonavir-boosted protease inhibitor vs TDF + NNRTI (hazard ratio [HR] 2.15, 95% CI, 1.3–3.6; =.004). The increased risk was seen considering both initial and current regimens. Findings from the undadjusted Cox model also showed a higher CKD risk in the TDF with a ritonavir-boosted protease inhibitor group (HR 3.14, 95% CI, 1.4–7.0) vs TDF + NNRTI. 

Lead author Lise Cuzin added, “Our analysis revealed a clinician-driven switch away from TDF among persons experiencing a decline in renal function while receiving this drug.” 


Cuzin L, Pugliese P, Allavena C, et al. Antiretroviral therapy as a risk factor for chronic kidney disease: results from traditional regression modeling and causal approach in a large obsevational study. PLoS One. 2017;12(12):e0187517. 

This article originally appeared on MPR