Néphrotoxicité des antirétroviraux autres que le ténofovir

Abstract

The remarkable improvement of the outcome of HIV infection came with the price of substantial toxicity of some antiretrovirals. The first molecules used to treat HIV included an important nephrotoxicity. Zalcitabine, stavudine and didanosine can induce severe lactic acidosis. Lactate production is enhanced and the renal capacity to regulate pH is overwhelmed. However, this side effect is not due to a direct dysfunction of the kidneys. Zalcitabine was withdrawn from the market because of this risk. Indinavir, a protease inhibitor, is soluble only in very acidic solutions. Consequently, the small fraction that is excreted in the urine precipitates and can be responsible for uro-nephrolithiasis, leukocyturia, cristalluria, obstructive acute kidney failure, and acute or chronic interstitial nephritis. This is the reason why indinavir is almost not prescribed nowadays, even if it is still marketed. In addition to the direct nephrotoxicity of some antiretrovirals, anti-HIV treatment also includes a toxicity which pathophysiology is not completely elucidated. This nephrotoxicity is the consequence of organ accelerated ageing and of an increased vascular risk. Kidney vascularization (from renal arteries to capillaries) is essential to kidney function and all cardiovascular risks are also renal risks. It is now clearly established that combined antiretroviral treatment increases the vascular risk. A better comprehension of the links between HIV infection, its treatment and very long-term kidney risk is needed to improve the complex management of patients who have now cumulated several decades of HIV infection and treatment with various toxicities.