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A risk score for chronic kidney disease can inform choice of HIV medications

PLOS

Both traditional and HIV-related risk factors can predict the likelihood of developing chronic kidney disease (CKD), according to a study published this week in PLOS Medicine. In the study, Amanda Mocroft, of University College London, United Kingdom, and colleagues developed and validated a risk score model that can help inform choices among antiretroviral drugs for patients with HIV.

Antiretroviral therapy can help control HIV, extending the life expectancy of those with the virus. However, some antiretroviral drugs may be nephrotoxic (harmful to the kidney), increasing the risk of CKD. Mocroft and colleagues used clinical and demographic data from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study to develop a CKD risk score model based on nine factors (age, intravenous drug use, hepatitis C co-infection, estimated glomerular filtration rate (a measure of kidney function), gender, nadir CD4 count (a measure of severity of immune system damage prior to treatment for HIV), hypertension, diabetes, and cardiovascular disease). They found that study participants with characteristics that resulted in a low risk score had a 1 in 393 chance of developing CKD in the following five years, while participants with medium and high risk scores had a 1 in 47 and 1 in 6 chance, respectively, of developing CKD. The researchers were also able to determine the added risk of using potentially nephrotoxic antiretroviral drugs.

For an additional patient to develop CKD within five years, the number of patients in the low risk group that would have to be treated with the antiretroviral drugs tenofovir, atazanavir/ritonavir, or another boosted (combined with ritonavir to increase blood levels) protease inhibitor (not including lopinavir/ritonavir) was 739. That "number needed to harm" (NNTH) was 88 and 9 in the medium and high risk groups, respectively. Treatment with unboosted atazanavir, or lopinavir/ritonavir added less potential harm, resulting in higher NNTH: 1702, 202, and 21 for the low, medium and high risk groups. The researchers validated this risk score using two independent HIV study groups, but note that they were not able to fully incorporate data on race, or include data on the presence of protein in urine (a common screening test for kidney injury) into the model.

The authors say this risk score "has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD, and to identify those at greatest risk of CKD." A tool for calculating risk using their model is available online http://hivpv.org/Home/Tools/ChronicKidneyDiseaseTool.aspx.

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Funding: Data on Adverse Events (D:A:D) Study: The D:A:D study was supported by the Highly Active Antiretroviral Therapy Oversight Committee (HAARTOC) , a collaborative committee with representation from academic institutions, the European Agency for the Evaluation of Medicinal Products, the United States Food and Drug Administration, the patient community, and all pharmaceutical companies with licensed anti-HIV drugs in the European Union: AbbVie, Boehringer Ingelheim Pharmaceuticals Inc., Bristol-Myers Squibb, Gilead Sciences Inc., ViiV Healthcare, Merck & Co Inc., Pfizer Inc, F. HoffmanLaRoche Ltd and Janssen Pharmaceuticals. Supported also by a grant [grant number DNRF126] from the Danish National Research Foundation to CHIP, Supported by a grant [grant number CURE/97- 46486] from the Health Insurance Fund Council, Amstelveen, the Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA [grant number Action Coordonnée no.7, Cohortes], to the Aquitaine Cohort; The Australian HIV Observational Database (AHOD) is funded as part of the Asia Pacific HIV Observational Database, a program of The Foundation for AIDS Research, amfAR, and is supported in part by a grant from the U.S. National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) [grant number U01-AI069907] and by unconditional grants from Merck Sharp & Dohme; Gilead Sciences; Bristol-Myers Squibb; Boehringer Ingelheim Pharmaceuticals Inc.; Roche; Pfizer; GlaxoSmithKline; Janssen Pharmaceuticals. The Kirby Institute is funded by The Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales.

By grants from the Fondo de Investigación Sanitaria [grant number FIS 99/0887] and Fundación para la Investigación y la Prevención del SIDA en Espanã [grant number FIPSE 3171/00], to the Barcelona Antiretroviral Surveillance Study (BASS); by the National Institute of Allergy and Infectious Diseases, National Institutes of Health [grants number 5U01AI042170-10 , 5U01AI046362-03], to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); by grants from the BIOMED 1 [grant number CT94- 1637] and BIOMED 2 [grant number CT97-2713] programs and the fifth framework program [grant number QLK2-2000-00773] of the European Commission and grants from Bristol-Myers Squibb, GlaxoSmithKline, Boehringer Ingelheim Pharmaceuticals Inc. and Roche, to the EuroSIDA study; by unrestricted educational grants of Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences Inc., GSK, Pfizer Inc., Janssen Pharmaceuticals to the Italian Cohort Naive to Antiretrovirals (The ICONA Foundation); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS).

The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above. SMART/ESPRIT: These studies were funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health [grant numbers UM1-AI068641, U01-AI042170 and U01-AI46362 (SMART); U01-AI46957 and U01- AI068641 (ESPRIT)]. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: PM: honoraria or travel/ meeting expenses from Bristol-Myers Squibb, Gilead, Janssen-Cilag, Merck Sharp & Dohme-Chibret and ViiV Healthcare in the past five years. ML received unrestricted grants to my institution from Boehringer Ingelhiem, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, Janssen-Cilag, ViiV HealthCare. CS has received funds for preparation of Educational Materials from Janssen, Gilead, BMS, ViiV HealthCare, support for attendance at Ad board and support to attend HIV conference from Gilead, funding to conduct study from BMS. OM has received honoraria as a speaker from Abbott and Gilead Sciences, serves on the board of Roche, and had expenses paid by Roche and Baxter for travel, accommodations, and meetings. OK has received honoraria, consultancy, lecture fees, and travel grants from Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck Sharp & Dohme, Roche, and ViiV Healthcare, and has served/is serving on Advisory Boards for Gilead Sciences, Merck Sharp & Dohme, and ViiV Healthcare. AM has received honoraria, consultancy, lecture fees, and travel grants from Gilead Sciences, Merck Sharp & Dohme, Boehringer Ingelheim, Pfizer and GSK.

Citation: Mocroft A, Lundgren JD, Ross M, Law M, Reiss P, Kirk O, et al. (2015) Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study. PLoS Med 12(3): e1001809. doi:10.1371/journal.pmed.1001809

Author Affiliations:

University College London, UNITED KINGDOM
University of Copenhagen, DENMARK
Mount Sinai School of Medicine, UNITED STATES
University of New South Wales, AUSTRALIA
University of Amsterdam, THE NETHERLANDS
University of Minnesota, UNITED STATES
Kantonsspital Aarau, SWITZERLAND
Centre Hospitalier Universitaire de Nice, FRANCE
Universite de Bordeaux, FRANCE
Royal Free London NHS Foundation Trust, UNITED KINGDOM

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http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001809

Contact:

Amanda Mocroft
University College London Medical School
UNITED KINGDOM
+44 2077 940 0500 extension 33194
a.mocroft@ucl.ac.uk

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