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April 2016

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*January 1-March 31, 2016
What We're Reading
Predicting Kidney Disease Risk to Guide ART Selection
Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

Kidney disease is common among people living with HIV. Multiple factors, including HIV-associated nephropathy, antiretroviral therapy (ART), hepatitis B (HBV) or C (HCV) virus coinfection, diabetes, hypertension, and primary kidney disease can cause or contribute to kidney dysfunction. More common factors, though, are transient fluctuations in serum creatinine and estimated glomerular filtration rate (eGFR). Reducing the occurrence of comorbidities associated with kidney disease and limiting the diagnostic uncertainty of eGFR fluctuations may influence ART-prescribing decisions.
 
In a recently published article [AIDS 2016; PMID 26891036], Flandre and colleagues report on the relationship between various initial ART regimens and the risk of chronic kidney disease (CKD). The researchers used a predictive score, developed and validated through the D:A:D cohort, that defined CKD as a persistent eGFR <60 mL per min per 1.73 m2.
 
The study cohort included 6,301 patients receiving care at 12 reference centers in France, all of whom initiated ART after January 1, 2004. All patients had at least one pre-ART and two on-ART creatinine measures, and eGFR was determined with the MDRD equation. Patients were stratified into low, medium, and high risk for CKD using the D:A:D score for CKD. This score accounts for a wide variety of factors, including type of HIV exposure (injection drug use [IDU] vs non-IDU), HCV coinfection, age, pre-ART eGFR, sex, nadir CD4 count, hypertension, cardiovascular disease, and diabetes. Incident CKD occurred in 211 (3.4%) of participants and was associated with older age, lower pre-ART eGFR, and lower nadir CD4 count. The probability of CKD by risk score was as follows: low risk, 0.65%; medium risk, 4.6%; and high risk, 15.9%.
 
CKD risk was highest for patients receiving a boosted protease inhibitor (PI) with tenofovir disoproxil fumarate (TDF). Risk was lower for patients receiving a non-nucleoside reverse transcriptase inhibitor (NNRTI) with or without TDF. Notably, among low-risk patients, the choice of an NNRTI vs a PI or TDF vs no TDF made no apparent difference in CKD risk.
 
This study is helpful in assessing the appropriateness of TDF or boosted-PI regimens for specific patients. For instance, avoidance of an initial ART regimen that includes TDF or a boosted-PI may be best for patients with a high D:A:D score for CKD. Patients with a low CKD risk score do not appear at increased risk for CKD from TDF or boosted PIs. These types of data may also be useful in securing insurer authorization to prescribe specific medications, such as tenofovir alafenamide (TAF)-containing combination tablets, and in discussing ART regimen side-effect profiles with patients.

Taking a risk-based approach when choosing an ART regimen does not require actual calculation, but taking into account a patient's D:A:D score and risk factors for CKD is encouraged. Such an approach may reduce the number of patients requiring switches to less nephrotoxic regimens due to elevated eGFRs and may reduce the incidence of CKD among people living with HIV.
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New York State Department of Health AIDS Institute
In collaboration with JHU School of Medicine, Division of Infectious Diseases
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