Antiretroviral therapy and the kidney: Balancing benefit and risk in patients with HIV-infection. Review

Advances in the pharmacologic management of HIV-infection continue at a rapid pace. Currently, more than 30 antiretroviral drugs (ARVDs) and their combinations are available. The use of these drugs can suppress HIV viral load to an inconspicuous level and increase the life expectancy of HIV-infected people. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non-HIV-associated comorbidities, which may be observed earlier than in age-matched controls. Although most ARVDs are relatively free of renal toxicity, drug-related kidney damage can occur and may need to be distinguished from the progression of HIV-related kidney diseases, other infections (e.g., hepatitis C), or kidney diseases unrelated to HIV-infection and its treatment. The most common nephrotoxic effects associated with antiretroviral therapy (ART) include acute kidney injury, crystal-induced obstruction and kidney stone disease secondary to use of protease inhibitors (mainly indinavir and atazanavir), and proximal tubule damage related to the nucleotide analog reverse transcriptase inhibitor tenofovir. Finally, nonspecific metabolic complications might increase the risk of vascular chronic kidney disease (CKD) in patients on ART. Renal impairment usually develops under conditions of repeated treatment and may not always be attributed to a specific drug therefore, in patients with HIV receiving any ARVDs, renal function should be regularly monitored. Given the benefits of ART, fear of nephrotoxic effects is never a valid reason for not using it. Identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modification, close monitoring, and avoidance or cautious use of potentially nephrotoxic medications. Given the prevalence of CKD, a wide range of possible interactions between HIV, ARVDs, CKD, and its treatments, nephrologists need to be aware of the possible effects of ART on the kidneys. The review addresses issues related to the mechanisms, risk factors, and clinical manifestations of renal damage with medications to assess the clinical situation during antiretroviral therapy and discusses measures to prevent their nephrotoxicity.

ВИЧ-инфекция, повреждение почек, антиретровирусные препараты, антиретровирусная терапия, нефротоксичность, факторы риска, профилактика, HIV-infection, renal damage, review, antiretroviral drugs, antiretroviral therapy, nephrotoxicity, risk factors, preventive measures

1. WHO. Global Health Sector Strategy for the Elimination of HIV, 2016-2021. Available online: https://apps.who.int/iris/bitstream/handle/10665/255763/WHO-HIV-2016.05.

2. WHO. Data and Statistics. Available online: http://www.who.int/hiv/data/en/ (accessed on 9 July 2019).

3. ФНМЦ по профилактике и борьбе со СПИДом при Центральном НИИ эпидемиологии Роспотребнадзора: https://vademec.ru/news/2020/02/26/rospotrebnadzor-v-2019-godu-ot-vich-assotsiirovannykh-zabolevaniy-umerli-33-6-tysyachi-rossiyan/

4. Беляков Н.А., Рассохин В.В. Коморбидные состояния при ВИЧ-инфекции. Часть 1. Основы проблемы. СПб.: Балтийский медицинский образовательный центр, 2018. 184 с.

5. Gueler A., Moser A., Calmy A. et al. Swiss HIV Cohort Study, Swiss National Cohort. Life expectancy in HIV-positive persons in Switzerland: Matched comparison with general population. AIDS Lond. Engl. 2017; 31: 427-436. doi: 10.1097/QAD.0000000000001335.

6. Liyanage T., Ninomiya T., Jha V. et al. Worldwide access to treatment for end-stage kidney disease: a systematic review. The Lancet. 2015; 385(9981):1975-82.

7. Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017; 4:e349-e356.

8. Sabin C.A. Do people with HIV infection have a normal life expectancy in the era of combination antiretroviral therapy. BMC Med. 2013; 11,251.

9. Jotwani V., Li Y., Grunfeld C. et al. Risk factors for ESRD in HIV-infected individuals: traditional and HIV-related risk factors. Am J Kidney Dis. 2012; 59: 628-635.

10. Ryom L., Mocroft A., Kirk O. еt al. D:A: D Study Group. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D: A: D study. J Infect Dis. 2013; 207: 1359-69.

11. Bertoldi A., De Crignis E., Miserocchi A. et al. HIV and kidney: a dangerous liaison. New Microbiol. 2017; 40: 1-10.

12. HIV 2015/2016. Hoffman C., Rockstroh J. Hamburg: Medicin Focus Verlag, 2015. 756 s. URL: www.hivbook.com.

13. Lucas G.M., Ross M.J., Stock P.G. et al. Clinical practice guidelines for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59: e96-138. doi: 10.1093/cid/ciu617.

14. Swanepoel C.R., Atta M.G., D’Agati V.D. et al. Conference Participants: Kidney disease in the setting of HIV infection: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2018; 93: 545-559.

15. Milburn J., Jones R., Levy J.B. Renal effect of novel antiretroviral drugs. Nephrol Dial Transplant. 2017; 32:434-439.

16. AIDSinfo. Guidelines for the use of Antiretroviral Agents in HIV-1 infected Adults and Adolescents 2016 16-th November 2016. https://aidsinfo.nih.gov/contentfiles/lvguidelines/AA_Recommendations.pdf.

17. ВИЧ-инфекция и СПИД: национальное руководство. Под ред. В.В. Покровского. М.: ГЭОТАР-Медиа, 2020. 696 с.

18. EACS European AIDS Clinical Society Guidelines, version 9.1. October 2018. URL: http: // www.eacsociety.org.

19. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. October 25. 2018. URL: http: // AIDSinfo.nih.gov.

20. Atta M.G., De Seigneux S., Lucas G.M. Clinical Pharmacology in HIV Therapy. Clin J Am Soc Nephrol. 2019: 14:435-444. doi: https://doi.org/10.2215/CJN.02240218

21. Izzedine H., Harris M., Perazella M. et al. The nephrotoxic effects of HAART. Nat. Rev. Nephrol. 2009; 5: 563-573.

22. Ryom L., Mocroft A., Lundgren J. HIV therapies and the kidney: some good, some not so good? Curr HIV/AIDS Rep. 2012; 9: 111-20.

23. Volberding P.A., Deeks S.G. Antiretroviral therapy and management of HIV infection. Lancet. 2010; 376: 49-62.

24. Pedersen K.K., Pedersen M., Troseid M. et al. Microbial translocation in HIV infection is associated with dyslipidemia, insulin resistance, and risk of myocardial infarction. J Acquir Immune Defic Syndr. 2013; 64: 425-433.

25. Guaraldi G., Orlando G., Zona S. еt al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011; 53: 1120-6.

26. Halle M.P., Oumarou M., Kaze Folefack F. et al. Prevalence and associated factors of chronic kidney disease among patients infected with human immunodeficiency virus in Cameroon. Iran J Kidney Dis. 2018; 12: 268-74.

27. Mdodo R., Frazier E.L., Dube S.R. et al. Cigarette smoking prevalence among adults with HIV compared with the general adult population in the United States: cross-sectional surveys. Ann Intern Med. 2015; 162: 335-344.

28. James M.T., Grams M.E., Woodward M. et al. A meta-analysis of the association of estimated GFR, albuminuria, diabetes mellitus, and hypertension with acute kidney injury. Am J Kidney Dis. 2015; 66: 602-612.

29. Rho M., Perazella M. A. Nephrotoxicity associated with antiretroviral therapy in HIV infected patients. Curr. Drug Saf. 2007; 2: 147-154.

30. Doshi S. Ucanda M., Hart R. et al. Incidence and Risk Factors for Renal Disease in an Outpatient Cohort of HIV-Infected Patients on Antiretroviral Therapy. Kidney Int Rep. 2019; 4: 1075-1084. doi.org/10.1016/j.ekir.2019.04.024.

31. Caires R.A., Silva V.T., Burdmann E. et al. Drug-induced acute kidney injury. In: Ronco C, Bellomo R, Kellum JA, Ricci Z, eds. Critical care nephrology. 3rd ed. Philadelphia: Elsevier; 2019. p. 214-21.

32. Yombi J.C., Pozniak A, Boffito M, еt al. Antiretrovirals and the kidney in current clinical practice: renal pharmacokinetics, alterations of renal function and renal toxicity. AIDS. 2014; 28: 621-32.

33. Post F. Adverse events: ART and the kidney: alterations in renal function and renal toxicity. J Int AIDS Soc. 2014; 17: 19513.

34. Jao J., Wyatt C. Antiretroviral medications: adverse effects on the kidney. Adv Chronic Kidney Dis. 2010; 17(1):72-82.

35. Lyseng-Williamson K.A., Reynolds N.A., Plosker G.L. Tenofovir disoproxil fumarate: A review of its use in the management of HIV infection. Drugs. 2005; 65: 413-432.

36. Smith P.F., DiCenzo R., Morse G.D. Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Clin Pharmacokinet. 2001; 40: 893-905.

37. Scherzer R., Estrella M., Li Y. et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012; 26: 867-875.

38. Клиническая фармакология: учебник. Под ред. В.Г. Кукеса. М.: ГЕОТАР-Медиа, 2008. 1056 с.

39. Arakawa H., Washio I., Matsuoka N. et al. Usefulness of kidney slices for functional analysis of apical reabsorptive transporters. Sci Rep. 2017; 7:12814. https://doi.org/10.1038/s41598-017-12828-z

40. Breda P.C., Wiech T., Meyer-Schwesinger C. et al. Renal proximal tubular epithelial cells exert immunomodulatory function by driving inflammatory CD4+ T cell responses. Am J Physiol Renal Physiol. 2019; 317(1):F77-F89. https://doi.org/10.1152/ajprenal.00427.2018

41. Nigam SK., Wu W., Bush K.T. Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters. Clin J Am Soc Nephrol. 2015; 10(11):2039-2049. https://doi.org/10.2215/cjn.02440314

42. Nieskens T.T.G., Peters J.G.P., Schreurs M.J. et al. A human renal proximal tubule cell line with stable organic anion transporter 1 and 3 expression predictive for antiviral-induced toxicity. AAPS J. 2016; 18:465-475. https://doi.org/10.1208/s12248-016-9871-8

43. Aschauer L., Limonciel A., Wilmes A. et al. Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: a transcriptomic study. Toxicol In Vitro. 2015; 30:106-116. https://doi.org/10.1016/J.TIV.2014.10.005

44. Czerniecki S.M., Cruz N.M., Harder J.L. et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell. 2018; 22(6):929.e4-940.e4. https://doi.org/10.1016/j.stem.2018.04.022

45. Perazella M.A. Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol. 2009;4(7):1275-83.

46. Perazella M.A. Pharmacology behind common drug nephrotoxicities. Clin J Am Soc Nephrol. 2018; 13(12):1897-908.

47. Siddama A, Suneel I.M. Drug Induced Kidney Disease. Open Acc J of Toxicol. 2017; 2(1): 555576. DOI: 10.19080/ OAJT.2017.02.555576.

48. Ciarimboli G. Individual P.K. C phosphorylation sites in organic cation transporter 1 determine substrate selectivity and transport regulation. J. Am. Soc. Nephrol. 2005; 16: 1562-1570.

49. Dasgupta A., Okhuysen P.C. Pharmacokinetic and other drug interactions in patients with AIDS. Ther Drug Monit. 2001; 23: 591-605.

50. Ibrahim F., Naftalin C., Cheserem E. et al. Immunodeficiency and renal impairment are risk factors for HIV-associated acute renal failure. AIDS. 2010; 24: 2239-2244.

51. Hsu C.Y., Ordonez J.D., Chertow G.M. et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int. 2008; 74: 101-107.

52. Lescure F., Flateau C., Pacanowski J. et al. HIV-associated kidney glomerular diseases: changes with time and HAART. Nephrol Dial Transplant. 2012; 27: 2349-2355.

53. Ross M.J. Advances in the pathogenesis of HIV-associated kidney diseases. Kidney Int. 2014; 86: 266-74.

54. Barnett L.M.A., Cummings B.S. Nephrotoxicity and renal pathophysiology: a contemporary perspective. Toxicol Sci. 2018; 164:379-390. https://doi.org/10.1093/toxsci/kfy159

55. Andreucci M., Faga T., Pisani A. et al. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice. Eur J Intern Med. 2017; 39:1-8. https://doi.org/10.1016/j.ejim.2016.12.001

56. Barnett L.M.A., Cummings B.S. Nephrotoxicity and renal pathophysiology: a contemporary perspective. Toxicol Sci. 2018; 164:379-390. https://doi.org/10.1093/toxsci/kfy159

57. Caires R.A., Silva V.T., Burdmann E. et al. Drug-induced acute kidney injury. In: Ronco C, Bellomo R, Kellum JA, Ricci Z, eds. Critical care nephrology. 3rd ed. Philadelphia: Elsevier; 2019. P.214-21

58. Roe J., Campbell L. J., Ibrahim F. et al. HIV care and the incidence of acute renal failure. Clin. Infect. Dis. 2008; 47: 242-249.

59. Wyatt C.M., Arons R.R., Klotman P.E. et al. Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality. AIDS 2006; 20(4): 561-565.

60. Peraldi M. N., Maslo C., Akposso K. et al. Acute renal failure in the course of HIV infection: a single-institution retrospective study of ninety-two patients and sixty renal biopsies. Nephrol. Dial. Transplant.1999; 14: 1578-1585.

61. Overton E.T., Nurutdinova D., Freeman J. et al. Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy. HIV Med. 2009; 10: 343-350.

62. Reiter W.J., Schon-Pernerstorfer H., Dorfinger K. et al. Frequency of urolithiasis in individuals seropositive for human immunodeficiency virus treated with indinavir is higher than previously assumed. J Urol. 1999; 161: 1082-1084.

63. Jafari A., Khalili H., Dashti-Khavidaki S. Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention. Eur J Clin Pharmacol. 2014; 70(9):1029-1040. https://doi.org/10.1007/s00228-014-1712-z

64. Jaradat M., Phillips C., Yum M.N. et al. Acute tubulointerstitial nephritis attributable to indinavir therapy. Am J Kidney Dis. 2000; 35: 16.

65. Sarcletti M., Petter A., Romani N. et al. Pyuria in patients treated with indinavir is associated with renal dysfunction. Clin Nephrol. 2000; 54: 261-270.

66. Cattelan A.M., Trevenzoli M., Naso A. et al. Severe hypertension and renal atrophy associated with indinavir. Clin Infect Dis. 2000; 30: 619-21.

67. Chan-Tack K.M., Truffa M.M., Struble K.A. et al. Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration’s Adverse Event Reporting System. AIDS. 2007; 21 (9): 1215-1218.

68. Krishnan M., Nair R., Haas M. et al. Acute renal failure in an HIV-positive50-year-old man. Am. J. Kidney Dis. 2000; 36: 1075-1078.

69. Angel-Moreno-Maroto A., Suarez-Castellano L., Hernandez-Cabrera M. et al. Severe efavirenz-induced hypersensitivity syndrome (not-DRESS) with acute renal failure. J. Infect. 2006; 52: 39-40.

70. Brewster U. C., Perazella M. A. Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. Am. J. Kidney Dis. 2004; 44: 81-84.

71. Hara M., Suganuma A., Yanagisawa N. et al. Atazanavir nephrotoxicity. Clin Kidney J. 2015; 8(2):137-142. https://doi.org/10.1093/ckj/sfv015

72. Jose S., Nelson M., Phillips A. et al. Improved kidney function in patients who switch their protease inhibitor from atazanavir or lopinavir to darunavir. AIDS. 2017; 31: 485-492.

73. Shafi T., Choi M.J., Racusen L.C. et al. Ritonavir-induced acute kidney injury: kidney biopsy findings and review of literature. Clin Nephrol. 2011; 75: 60-64.

74. Chughlay M.F., Njuguna C., Cohen K. et al. Acute interstitial nephritis caused by lopinavir/ritonavir in a surgeon receiving antiretroviral postexposure prophylaxis. AIDS. 2015; 29: 503-504.

75. Knudtson E., Para M., Boswell H. et al. Drug rash with eosinophilia and systemic symptoms syndrome and renal toxicity with a nevirapine-containing regimen in a pregnant patient with human immunodeficiency virus. Obstet Gynecol. 2003; 101: 1094-1097.

76. Zimmermann A.E., Pizzoferrato T., Bedford J. et al. Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis. 2006; 42 (2): 283-290.

77. Verhelst D., Monge M., Meynard J.L. et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis. 2002; 40 (6): 1331-1333.

78. Waheed S., Attia D., Estrella M.M. et al. Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: a case series. Clin Kidney J. 2015; 8: 420-425.

79. Aloy B., Tazi I., Bagnis C. еt al. Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev. 2016; 18(4): 184-92.

80. Ray A.S., Fordyce M.W., Hitchcock M.J. Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of human immunodeficiency virus. Antiviral Res. 2016; 125:63-70.

81. Izzedine H., Hulot J.S., Vittecoq D. et al. Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1- infected patients: data from a double-blind randomized active- controlled multicentre study. Nephrol Dial Transplant. 2005; 20 (4): 743-746.

82. Maggi P., Montinaro V., Mussini C. et al. Novel antiretroviral drugs and renal function monitoring of HIV patients. AIDS Rev. 2014; 16: 144-151.

83. Harris M. Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients. Expert Opin. Drug. Saf. 2008; 7: 389-400.

84. Gallant J.E., Staszewski S., Pozniak A. et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA. 2004; 292 (2): 191-201.

85. Crane H.M., Kestenbaum B., Harrngton R.D. et al. Amprenavir and didanosine are associated with declining kidney function among patients receiving tenofovir. AIDS. 2007; 21(11): 1431-1439.

86. Mocroft A., Lundgren J.D., Ross M. et al. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016; 3:e23-32.

87. Tanuma J., Jiamsakul A., Makane A. et al. Renal dysfunction during tenofovir use in a regional cohort of HIV-infected individuals in the Asia-Pacific. PLoS One. 2016; 11: e0161562.

88. Joshi M. K., Liu H. H. Acute rhabdomyolysis and renal failure in HIV-infected patients: risk factors, presentation, and pathophysiology.AIDS Patient Care STDs. 2000; 14: 541-548.

89. Castro J.G., Gutierrez L. Rhabdomyolysis with acute renal failure probably related to the interaction of atorvastatin and delavirdine. Am J Med. 2002; 112: 505.

90. Guder W.G., Hofmann W. Clinical role of urinary low molecular weight proteins: their diagnostic and prognostic implications. Scand J Clin Lab Invest Suppl. 2008; 241: 95-8.

91. Gatanaga H., Tachikawa N., Kikuchi Y. et al. Urinary beta2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil fumarate. AIDS. Res Hum Retroviruses. 2006 Aug;22(8): 744-8.

92. Woodward C.L., Hall A.M., Williams I.G. et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009; 10:482-487.

93. Waheed S., Attia D., Estrella M.M. et al. Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: a case series. Clin Kidney J. 2015; 8: 420-425.

94. Hamzah L., Booth J.W., Jose S. et al. Renal tubular disease in the era of combination antiretroviral therapy. AIDS. 2015; 29: 1831-1836.

95. Gupta S. K. Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS. 2008; 22, 99-103.

96. Izzedine H., Launay-Vacher V., Deray G. Antiviral drug-induced nephrotoxicity. Am J Kidney Dis. 2005; 45: 804-817.

97. Samuels R., Bayerri C.R., Sayer J.A. et al. Tenofovir disoproxil fumarate associated renal tubular dysfunction: noninvasive assessment of mitochondrial injury. AIDS. 2017; 31:1297-1301.

98. Hamzah L., Jose S., Booth J.W. et al. Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate. J Infect. 2017; 74: 492-500.

99. Stray K.M., Bam R.A., Birkus G. et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Agents Chemother. 2013; 58: 4982-4989.

100. German P., Liu H.C., Szwarcberg J. et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr. 2014; 61: 32-40.

101. Buchacz K., Young B., Baker R.K. et al. Renal function in patients receiving tenofovir with ritonavir/lopinavir or ritonavir/atazanavir in the HIV Outpatient Study (HOPS) cohort. J Acquir Immune Defic Syndr. 2006; 43: 626-628.

102. Calza L., Trapani F., Salvadori C. et al. Incidence of renal toxicity in HIV-infected, antiretroviral-naive patients starting tenofovir/emtricitabine associated with efavirenz, atazanavir/ritonavir, or lopinavir/ritonavir. Scand J Infect Dis. 2013; 45: 147-154.

103. Selvaraj S., Ghebremichael M., Li M. et al. Antiretroviral therapy-induced mitochondrial toxicity: potential mechanisms beyond polymerase-g inhibition. Clin Pharmacol Ther. 2014; 96: 110-120.

104. Woodward C.L., Hall A.M., Williams I.G. et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009; 10: 482-7.

105. James C.W., Steinhaus M.C., Szabo S. et al. Tenofovir-related nephrotoxicity: Case report and review of the literature. Pharmacotherapy. 2004; 24: 415-418.

106. Cattaneo D., Gervasoni C. Novel Antiretroviral Drugs in Patients with Renal Impairment: Clinical and Pharmacokinetic Considerations. Eur J Drug Metab Pharmacokinet. 2017; 42(4): 559-572. doi: 10.1007/s13318-016-0394-6.

107. Yanagisawa K., Nagano D., Ogawa Y. еt al. Raltegravir is safely used with long-term viral suppression for HIVinfected patients on hemodialysis: a pharmacokinetic study. AIDS. 2016; 30: 970-972.

108. Stray K.M., Bam R.A., Birkus G. et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Agents Chemother. 2013; 57(10):4982. https://doi.org/10.1128/AAC.00712-13

109. Milburn J., Rachael Jeremy J., Levy B. Renal effects of novel antiretroviral drugs. Nephrol Dial Transplant. 2016; 0: 1-6. doi: 10.1093/ndt/gfw064

110. Gallant J.E., Daar E.S., Raffi F. et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, doubleblind, active-controlled phase 3 trial. Lancet HIV. 2016; 3: e158-e165.

111. Aloy B., Tazi I., Bagnis C. еt al. Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev. 2016; 18(4): 184-92.

112. Wang H., Lu X., Yang X. еt al. The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: meta-analysis. Medicine (Baltimore). 2016; 95: e5146.

113. Рost F.A., Tebas P., Clarke A. et al. Brief report: switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-Infected adults with renal impairment: 96-week results from a single-arm, multicenter, open-label phase 3 study. J Acquir Immune Defic Syndr. 2017; 74: 180-184.

114. Sax P.E., Wohl D., Yin M.T. et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate coformulated with elvitegravir, cobicistat and emtricitabine for initial treatment of HIV-1 infection: two randomised double blind phase 3 non-inferiority trials. Lancet. 2015; 385: 2606-2615.

115. Morris A.A., Baudouin S.V. Snow M.H. Renal tubular acidosis and hypophosphataemia after treatment with nucleoside reversetranscriptase inhibitors. AIDS. 2001; 15: 140-141.

116. Ahmad M. Abacavir-induced reversible Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiencysyndrome. J. Postgrad. 2006; 52: 296-297.

117. Seguro A. C. Effects of hypokalemia and hypomagnesemia on zidovudine (AZT) and didanosine (ddI) nephrotoxicity in rats. Clin.Nephrol. 2003; 59: 267-272.

118. Izzedine H., Lescure F.X., Bonnet F. HIV medication-based urolithiasis. Clin Kidney J. 2014; 7: 121-6.

119. Hortin G.L., King C., Miller K.D. et al. Detection of indinavir crystals in urine: dependence on method of analysis. Arch Pathol Lab Med. 2000; 124: 246-250.

120. Gagnon R.F., Tecimer S.N., Watters A.K. et al. Prospective study of urinalysis abnormalities in HIV-positive individuals treated with indinavir. Am J Kidney Dis. 2000; 36: 507-515.

121. Dieleman J.P., van Rossum A.M., Stricker B.C. et al. Persistent leukocyturia and loss of renal function in a prospectively monitored cohort of HIV-infected patients treated with indinavir. J Acquir Immune Defic Syndr. 2003; 32: 135-142.

122. Hamm M., Wawroschek F., Rathert P. Urinary cytology changes in protease inhibitor induced urolithiasis. J Urol. 2000; 163: 1249-1250.

123. Jaradat M., Phillips C., Yum M.N. et al. Acute tubulointerstitial nephritis attributable to indinavir therapy. Am J Kidney Dis. 2000; 35:16.

124. Tseng A., Seet J., Phillips E.J. The evolution of three decades of antiretroviral therapy: challenges, triumphs and the promise of the future. Br J Clin Pharmacol. 2015; 79: 182-94.

125. Hamada Y., Nishijima T., Watanabe K. et al. High incidence of renal stones among HIV-infected patients on ritonavir-boosted atazanavir than in those receiving other protease inhibitor-containing antiretroviral therapy. Clin Infect Dis. 2012; 55: 1262-1269.

126. Lafaurie M., De Sousa B., Ponscarme D.et al. Clinical features and risk factors for atazanavir (ATV)-associated urolithiasis: a case-control study. PLoS One. 2014; 9:e112836.

127. Valencia M.E., Moreno V. Atazanavir-induced nephrolithiasis. Enferm Infecc Microbiol Clin. 2009; 27(2):134-135.

128. Lastours V., De Silva E.F.R., Daudon M. et al. High levels of atazanavir and darunavir in urine and crystallyria in asymptomatic patients. J Antimicrob Chemother. 2013; 8: 1850-1856.

129. Gervasoni C., Meraviglia P., Minisci D. et al. Metabolic and kidney disordes correlate with atazanavir concentrations in HIV-infected patients: is it time to revise atazanavir dosage? PloS One. 2015; 4: е0123670.

130. Hou J., Nast C.C. Changing concepts of HIV infection and renal disease. Curr Opin Nephrol Hypertens. 2018; 27: 144-152.

131. Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group. KDIGO. clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2012; 2013(3): 1-150.

132. Kooij K.W., Vogt L., Wit F.W. et al. Higher prevalence and faster progression of chronic kidney disease in human immunodeficiency virus-infected middle-aged individuals compared with human immunodeficiency virus-uninfected controls. J Infect Dis. 2017; 216: 622-31.

133. Mocroft A., Lundgren J.D., Ross M. еt al. Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016; 3: e23-32.

134. Nakhoul G.N., Huang H., Arrigain S. et al. Serum potassium, end-stage renal disease and mortality in chronic kidney disease. Am J Nephrol. 2015; 41:456-463.

135. Luo J., Brunelli S., Jensen D.E., Yang A. Association between serum potassium and outcomes in patients with reduced kidney function. Clin J Am Soc Nephrol. 2016; 11:90-100.

136. Cirino C.M., Kan V.L. Hypokalemia in HIV patients on tenofovir. AIDS. 2006; 20 (12): 1671-1673.

137. Grant P.M., Kitch D., McComsey G.A. et al. Long-term Bone Mineral Density Changes in Antiretroviral-Treated HIV-Infected Individuals. J Infect Dis. 2016; 214:607-11. https://doi.org/10.1093/ infdis/jiw204.

138. Abd-Elmoniem K.Z., Unsal A.B., Eshera S. et al. Increased coronary vessel wall thickness in HIV-infected young adults. Clin Infect Dis. 2014; 59:1779-86. https://doi.org/10.1093/cid/ciu672.

139. Troll J.G. Approach to dyslipidemia, lipodystrophy, and cardiovascular risk in patients with HIV infection. Curr Atheroscler Rep. 2011; 13:51-6. https://doi.org/10.1007/ s11883-010-0152-1.

140. Achhra A.C., Nugent M., Mocroft A. et al. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals: Recent Developments. Curr HIV/AIDS Rep. 2016; 13(3): 149-57. doi: 10.1007/s11904-016-0315-y

141. Ryom L., Mocroft A., Kirk O. et al. Predictors of estimated glomerular filtration rate progression, stabilization or improvement after chronic renal impairment in HIV-positive individuals. AIDS. 2017; 31:1261-1270.

142. Estrada V., Portilla J. Dyslipidemia related to anti-retroviral therapy. AIDS Rev. 2011; 13(1):49-56.

143. Scherzer R., Gandhi M., Estrella M.M. et al. A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans. AIDS. 2014; 28: 1289-1295.

144. Gillard B.K., Raya J.L., Ruiz-Esponda R. et al. Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function. Arterioscler Thromb Vasc Biol. 2013; 33:1714-21. https://doi.org/10.1161/ATVBAHA.113.301538.

145. Cheng SH, Cheng CY, Sun NL. Lipid-lowering agents for dyslipidemia in patients who were infected with HIV in Taoyuan, Taiwan. J Int AIDS Soc. 2014; 17:19556. https:// doi.org/10.7448/IAS.17.4.19556.

146. Jevtovic D.J., Dragovic G., Salemovic D. et al. The metabolic syndrome, an epidemic among HIV-infected patients on HAART. Biomed Pharmacother. 2009; 63:337-42. https://doi.org/10.1016/j. biopha.2008.09.011.

147. Matoga M.M., Hosseinipour M.C., Aga E. et al. Hyperlipidaemia in HIV-infected patients on lopinavir/ritonavir monotherapy in resource-limited settings. Antivir Ther. 2017;22(3):205-213.

148. Chow D.C., Souza S.A., Chen R. et al. Elevated blood pressure in HIV-infected individuals receiving highly active antiretroviral therapy. HIV Clin Trials 2003; 4: 411-416.

149. Seaberg E.C., Munoz A., Lu M. et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS 2005; 19: 953-960.

150. Friis-Moller N., Weber R., Reiss P. et al. Cardiovascular disease risk factors in HIV patients-Association with antiretroviral therapy. Results from the DAD study. AIDS. 2003; 17: 1179-1193.

151. Crane H. M., Van Rompaey S. E., Kitahata M. M. Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy. AIDS. 2006; 20: 1019-1026.

152. Ekrikpo U., Kengne A., Bello A. et al. Chronic kidney disease in the global adult HIV-infected population: a systematic review and meta-analysis. PLoS One. 2018; 13: e0195443.

153. Dieleman J.P., van Rossum A.M., Stricker B.C. et al. Persistent leukocyturia and loss of renal function in a prospectively monitored cohort of HIV-infected patients treated with indinavir. J Acquir Immune Defic Syndr. 2003; 32: 135-142.

154. Rodriguez-Nóvoa S. Alvarez E., Labarga P. et al. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010; 9(4): 545-59.

155. Hara M., Suganuma A., Yanagisawa N. et al. Atazanavir nephrotoxicity. Clin Kidney J. 2015; 8: 137-142.

156. Schetz M., Dasta J., Goldstein S., Golper T. Drug-induced acute renal failure. Curr Opin Crit Care 2005; 11(6): 555-565.

157. Dube M., Fenton M. Lipid abnormalities. Clin Infect Dis. 2003; 36 (Suppl.2.), 79-83.

158. Rehman H., Kamal A.K., Morris P.B. et al. Mobile Health (mHealth) Technology for the Management of Hypertension and Hyperlipidemia: Slow Start but Loads of Potential. Curr Atheroscler Rep. 2017; 19:12. https://doi.org/10.1007/s11883-017-0649-y.

159. Husain N.E.O., Ahmed M.H. Managing dyslipidemia in HIV/AIDS patients: challenges and solutions. HIV/AIDS (Auckland, NZ). 2015;7:1-10.

160. Estrella M.M., Parekh R.S., Abraham A.J. et al. The impact of kidney function at highly active antiretroviral therapy initiation on mortality in HIV-infected women. Acquir Immune Defic Syndr. 2010; 55(2): 217-20.

161. Inker L.A., Wyatt C., Creamer R. et al. Performance of creatinine and cystatin C GFR estimating equations in an HIV-positive population on antiretrovirals. J Acquir Immune Defic Syndr. 2012; 61: 302-309.

162. Yombi J.C., Jones R., Poznia A. et al. Monitoring of kidney function in HIV-positive patients. HIV Med. 2015; 16: 457-467.

163. Lucas G.M., Cozzi-Lepri A., Wyatt C.M. et al. Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals. HIV Med. 2014; 15:116-123.

164. Mocroft A., Ryom L., Reiss P. et al. A comparision of estimated glomerular filtration rates using Cockcroft-Gaault and the Chronic Kidney Disease Epidemiology Collaboration estimating eguations in HIV infection. HIV Med. 2014; 144-152.

165. Hamzah L., Jones R., Post F.A. Optimizing antiretroviral regimens in chronic kidney disease. Curr Opin Infect Dis. 2019; 32: 1-7.

166. Matzke G.R., Aronoff G.R., Atkinson Jr. A.J. et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2011; 80(11):1122-37.

167. Barre.-Sinoussi F., Ross A.L, Delfraissy J.F. Past, present and future: 30 years of HIV research. Nat Rev Microbiol. 2013; 11: 8.77-83.

168. Personett H.A., Kayhart B.M., Barreto E.F. et al. Renal Recovery following Liposomal Amphotericin B-Induced Nephrotoxicity. Int J Nephrol. 2019, Article ID 8629891, 8 pages. https://doi.org/10.1155/2019/8629891

169. Roberts D.M., Smith M.W.H., McMullan B.J. et al. Acute kidney injury due to crystalluria following acute valacyclovir overdose. Kidney Intern. 2011; 79, 574; doi:10.1038/ki.2010.496

170. Fleischer R., Johnson M. Acyclovir nephrotoxicity: a case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy. Case Rep Med 2010; 2010. pii: 602783. doi:https://doi.org/10. 1155/2010/602783

171. Smith D.E., Hills D.A., Harman C. et al. Nebulized pentamidine for the prevention of Pneumocystis carinii pneumonia in AIDS patients: experience of 173 patients and a review of the literature. Q J Med. 1991; 80(291): 619-29.

172. Perazella M. Trimethoprim-induced hyperkalaemia: clinical data, mechanism, prevention and management. Drug Saf. 2000; 22 (3): 227-36.

173. Nickels L. C., Jones C., Stead L.G. Trimethoprim-Sulfamethoxazole-Induced Hyperkalemia in a Patient with Normal Renal Function. Case Reports in Emergency Medicine Volume 2012, Article ID 815907, 3 pages doi:10.1155/2012/815907

174. Fine D., Perazella M., Lucas G. et al. Renal disease in patients with HIV infection: epidemiology, рathogenesis and management. Drugs. 2008; 68 (7): 963-980.