What is the role of antiretroviral drugs in the etiology of HIV-related renal disorders?

Updated: May 09, 2018
  • Author: Moro O Salifu, MD, MPH, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Answer

Most HIV medications are well tolerated, even in the presence of renal insufficiency. [15]  The (potential) toxicity of the nucleoside reverse transcriptase inhibitors (NRTIs—ie, zidovudine, [16] didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine) uniformly manifests as type-B lactic acidosis. However, didanosine may cause electrolyte abnormalities, such as hypokalemia, hyponatremia, hypermagnesemia, and hyperuricemia, and stavudine may cause hyperuricemia.

Tenofovir disoproxil fumarate (tenofovir DF) is an NRTI with the potential for cumulative renal toxicity.3 Dose adjustment is indicated when creatinine clearance is less than 50 mL/min.

Except for nevirapine, which may cause lactic acidosis, the non-nucleoside reverse transcriptase inhibitors (ie, nevirapine, delavirdine, efavirenz, etravirine) have no reported significant renal toxicity.

As a class, the protease inhibitors (PIs) are the antiretroviral agents most strongly implicated in renal toxicity. [1]  PIs (ie, saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, fosamprenavir, lopinavir, atazanavir, tipranavir, darunavir) may precipitate nephrolithiasis. A classic form of this is crystalluria with the older agent indinavir, which occurs independently of renal function; however, the stones resolve after cessation of indinavir therapy. A study by Rockwood et al found that the rate of kidney stones was 7.3 per 1000 patient-years in patients receiving ritonavir-boosted atazanavir compared with 1.9 per 1000 patient years in patients receiving other commonly used antivirals. [17]

Enfuvirtide (Fuzeon) is the first of a newer class of fusion inhibitors that targets the gp41 protein on the surface of HIV and stops the virus from entering cells. Enfuvirtide has no known renal effects for creatinine clearance of greater than 35 mL/min.

Maraviroc (Selzentry) is also a fusion inhibitor. It blocks the CCR5 coreceptor on CD4+ cells, preventing the virus from entering. Maraviroc does not require dose adjustment for creatinine clearance greater than 50 mL/min.

Raltegravir (Isentress) is the first of a newer class of integrase strand transfer inhibitors. It does not require dose adjustment in patients with abnormal renal function.

Dose adjustment should be made in patients receiving NRTIs when the glomerular filtration rate falls below 50 mL/min. Patients receiving nonnucleoside reverse transcriptase inhibitors (NNRTIs) may also receive a dose adjustment when the glomerular filtration rate falls below 50 mL/min. No dose adjustment is required for patients taking protease inhibitors.


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