Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV
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People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm3 to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m2/year, with no significant difference between treatment arms (difference deferred – immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m2). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.
| Originalsprog | Engelsk |
|---|---|
| Bogserie | Kidney International |
| Vol/bind | 106 |
| Udgave nummer | 1 |
| Sider (fra-til) | 136-144 |
| Antal sider | 9 |
| ISSN | 0085-2538 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
The authors would like to thank the START Study participants for their longstanding contribution. The complete list of members of the START study group can be found in the Appendix of Lundgren et al.11, This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (UM1 AI 068641, UM1-AI120197, and U01 AI136780); the Department of Bioethics at the National Institutes of Health Clinical Center; the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; and the National Institute of Arthritis and Musculoskeletal Disorders. Financial support for START was also provided by the French Agence Nationale de Recherches sur le Sida et les H\u00E9patites Virales (ANRS); the German Ministry of Education and Research; the European AIDS Treatment Network (NEAT); the Australian National Health and Medical Research Council; and the UK Medical Research Council and National Institute for Health Research. Six pharmaceutical companies (AbbVie, Inc. Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck Sharp and Dohme Corp.) donated antiretroviral drugs to START. The authors were also supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK112258 to CMW).
Funding Information:
This work was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (UM1 AI 068641, UM1-AI120197, U01 AI136780); the Department of Bioethics at the NIH Clinical Center; the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; and the National Institute of Arthritis and Musculoskeletal Disorders. Financial support for START was also provided by the French Agence Nationale de Recherches sur le SIDA et les H\u00E9patites Virales (ANRS); the German Ministry of Education and Research; the European AIDS Treatment Network (NEAT); the Australian National Health and Medical Research Council; and the UK Medical Research Council and National Institute for Health Research. Six pharmaceutical companies (AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck Sharp and Dohme Corp.) donated antiretroviral drugs to START. The authors were also supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK112258 to CMW).
Publisher Copyright:
© 2024 International Society of Nephrology
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