HIV infection is associated with an increased risk of chronic kidney disease (CKD). Little is known about the contribution of HIV and antiretroviral therapy (ART) to CKD in asymptomatic HIV. We hypothesize that immediate initiation of ART in patients with high CD4+ cell counts will result in early improvements in clinically relevant markers of CKD, but that the early renal benefits will be partially offset by prolonged exposure to current first-line ART regimens with established nephrotoxic potential. We will test this hypothesis in an ancillary study to the Strategic Timing of AntiRetroviral Treatment (START) trial, a randomized trial investigating the impact of early versus deferred ART in treatment-nave individuals with CD4 > 500 cells/mm3. The randomized design of START offers a unique opportunity to directly compare the change in kidney function and markers of kidney injury between HIV-infected individuals who initiate ART immediately at high CD4 and similar individuals in whom ART is deferred. The prospective documentation of estimated glomerular filtration rate and availability of archived plasma and urine specimens will allow us to evaluate the impact of immediate ART on clinically relevant CKD outcomes and to refine existing risk scores for the prediction of CKD in HIV-positive individuals with high CD4.

Public Health Relevance

HIV infection is associated with increased risk of kidney disease. The goal of the proposed research is to better understand the contribution of HIV and its treatment to the risk of kidney disease in patients with asymptomatic HIV infection. Because kidney disease is a strong predictor of cardiovascular disease and death, the findings are expected to have a significant impact on morbidity and mortality in HIV-infected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK112258-02
Application #
9734824
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kimmel, Paul
Project Start
2018-07-01
Project End
2022-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Chan, Lili; Asriel, Benjamin; Eaton, Ellen F et al. (2018) Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug. Curr Opin Nephrol Hypertens 27:102-112
Achhra, Amit C; Mocroft, Amanda; Ross, Michael et al. (2017) Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. Int J Antimicrob Agents 50:453-460