Drug interaction after ritonavir discontinuation: considerations for antiretroviral therapy changes in renal transplant recipients

Abstract

Organ transplantation among people living with human immunodeficiency virus (PLHIV) is increasing. Guidelines recommend any changes in antiretroviral therapy (ART) prior to transplantation, but there are limited data regarding ART changes post transplantation. We report a case where an ART switch from a protease inhibitor-based regimen to dolutegravir plus emtricitabine/tenofovir alafenamide in a renal transplant recipient led to subtherapeutic tacrolimus concentrations and an increased serum creatinine (SCr). A workup for graft rejection was performed (including kidney biopsy and cytomegalovirus and BK virus polymerase chain reaction) following the rise in SCr, which was higher than expected from dolutegravir initiation (via organ cation transporter 2 inhibition). This case highlights the potential challenges of switching ART regimens in PLHIV post transplantation.

Keywords

HIV antiretroviral therapy combination ART treatment North America

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References

Fine

Perazella

Lucas

et al . Renal disease in patients with HIV infection: epidemiology, pathogenesis, and management. Drugs 2008; 68: 963–980.

Abraham

Althoff

Jing

et al . End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis 2015; 60: 941–949.

Atta

Gallant

Rahman

et al . Antiretroviral therapy in the treatment of HIV-associated nephropathy. Nephrol Dial Transplant 2006; 21: 2809–2813.

Lucas

Ross

Stock

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 Inf Dis. 2014; 59: e96–e138.

Department of Health and Human Services. Organ Procurement and Transplantation Network website, https://optn.transplant.hrsa.gov/learn/professional-education/hope-act/ (accessed 28 April 2018).

Maarseveen

Rogers

Trofe-Clark

et al . Drug-drug interactions between antiretroviral and immunosuppressive agents in HIV-infected patients after solid organ transplantation: a review. AIDS Patient Care STDS 2012; 26: 568–581.

Tricot

Teicher

Peytavin

et al . Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs. Am J Transplant 2009; 9: 1946–1952.

Iwasaki

Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet 2007; 22: 328–335.

AbbVie, Inc. Norvir (package insert). Chicago, IL: AbbVie, Inc, 2017.

10.

Bickel

Anadol

Vogel

et al . Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir. J Antimicrob Chemother 2010; 65: 999–1004.

11.

Mertz

Battegay

Marzolini

et al . Drug-drug interaction in a kidney transplant recipient receiving HIV salvage therapy and tacrolimus. Am J Kidney Dis 2009; 54: e1–e4.

12.

Horn

Hansten

Chan

LN.

Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother 2007; 41: 674–680.

13.

Stock

Barin

Murphy

et al . Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010; 363: 2004–2014.

14.

Locke

Mehta

Reed

et al . A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol 2015; 26: 2222–2229.

15.

Rosa

Suarez

Lorio

et al . Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: review of 58 cases. F1000Research 2016; 5: 1–12.

16.

Sawinski

Shelton

Mehta

et al . Impact of protease inhibitor-based anti-retroviral therapy on outcomes of HIV+ kidney transplant recipients. Am J Transplant 2017; 17: 3114–3122.

17.

Azar

Malinis

Moss

et al . Integrase strand transferase inhibitors: the preferred regimen in HIV-positive renal transplantation. Int J STD Aids 2017; 28: 447–458.

18.

Viiv Healthcare. Tivicay (package insert). Research Triangle Park, NC; Viiv Healthcare, 2013.

19.

Koteff

Borland

Chen

et al . A phase 1 study to evaluate the effects of dolutegravir on renal function via measurement of iohexol para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol 2012; 75: 990–996.

20.

Van Lunzen

Maggiolo

Arribas

et al . Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naïve adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging randomised, phase 2b trial. Lancet Infect Dis 2012; 12: 111–118.

21.

Raffi

Jaeger

Quiros-Roldan

et al . Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naïve adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet 2013; 13: 927–935.

22.

Walmsley

Antela

Clumeck

et al . Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med 2013; 369: 1807–1818.

23.

Clotet

Feinberg

Van Lunzen

et al . Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naïve adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet 2014; 383: 2222–2231.

24.

Cahn

Pozniak

Mingrone

et al . Dolutegravir versus raltegravir in antiretroviral –experiences, integrase-inhibitor naïve adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SALING study. Lancet 2013; 382: 700–708.

25.

Castagna

Maggiolo

Penco

et al . Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir resistant HIV-1: 24 week results of the phase III VIKING-3 study. J Infect Dis 2014; 210: 354–362.

26.

Lee

Malat

Bias

et al . Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus-positive kidney transplant recipient. Transpl Infect Dis 2016; 18: 625–627.

27.

Kastrup

Petersen

Bartram

et al . The effect of trimethoprim on serum creatinine. Br J Urol 1985; 57: 265–268.

28.

AR Scientific Inc. Bactrim (package insert). Philadelphia, PA; AR Scientific Inc., 2013.

29.

Pfizer. Lopid (package insert). New York, NY; Pfizer, 2008.

30.

Sax

Wohl

Yin

et al . Tenofovir alafenamide versus 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.

31.

Pozniak

Arribas

Gathe

et al.

Switching to tenofovir alafenamide, coformulated wth elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48 week results from a single-arm, multicenter, open-label phase 3 study. J Acquir Immune Defic Syndr 2016; 71: 530–537.

32.

Wohl

Thalme

Finlayson

et al. Renal safety of tenofovir alafenamide in patients at high risk of kidney disease. Poster presented at the conference on retroviruses and opportunistic infections, Boston, MA, 22–25 February 2016.

33.

Post

Tebas

Clarke

et al. Longer-term safety of tenofovir alafenamide in renal impairment. Poster presented at the conference on retroviruses and opportunistic infections, Boston, MA, 22–25 February 2016.

34.

Han

Guo

Cai

et al . Renal graft biopsy assists diagnosis and treatment of renal allograft dysfunction after kidney transplantation: a report of 106 cases. Int J Clin Exp Med 2015; 8: 4703–4707.

35.

Ahmad

Biopsy of the transplanted kidney. Semin Intervent Radiol 2004; 21: 275–281.

36.

Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Washington, DC: Department of Health and Human Services, 2018.