Last update:

   06-Jul-2004
 

Arch Hellen Med, 20(4), July-August 2003, 356-383

REVIEW

Antiviral drugs for the treatment of HIV-seropositive patients:
nephrotoxicity and dose adjustments in renal insufficiency

H. SAMBATAKOU
University of Manchester, Education and Research Centre, Wythenshawe Ηospital, UK,
and Infectious Diseases Unit, “G. Gennimatas” General Hospital, Athens, Greece

Patients with HIV infection and HIV-related opportunistic infections and malignancies are treated extensively with a broad spectrum of drugs. The introduction of new antiretroviral drugs, such as protease inhibitors and non nucleoside reverse transcriptase inhibitors, has changed the therapeutic options of these patients. On the other hand, renal dysfunction of varied etiology is also common in HIV-infected patients and can lead to endstage renal disease (ESRD). Renal disease occurs both as a primary manifestation of HIV infection (HIVAN) and secondary to complications such as concurrent illness or drug therapy. Great progress has been made in identifying specific glomerular lesions and their pathogenesis. Although the underlying mechanism and management of these disorders appear to be unclear and multifactorial, the newer antiretroviral agents show promise in preventing or resolving established renal disease. In contrast with previous years, more physicians are now encouraged by recent favorable results in managing patients with HIV infection and renal failure with more aggressive antiretroviral therapy. The knowledge of drug toxicity and pharmacokinetics in HIV (+) patients with renal insufficiency is therefore crucial. Some drugs used in HIV infection are excreted primarily by the kidney, other drugs such as foscarnet, adefovir, cidofovir are directly nephrotoxic, whereas acyclovir and indinavir may cause crystal-induced acute renal failure. This article reviews the types of nephrotoxicity which antiviral drugs may produce and the impact of renal impairment on the different phases of pharmacokinetics (bioavailability, distribution, protein-binding, metabolism, elimination) of antiviral drugs used in HIV disease. It provides recommendations for dose adjustments necessary to avoid subtherapeutic and/or toxic levels.

Key words: Antiviral drugs, HIV infection, Nephrotoxicity, Pharmacokinetics, Renal insufficiency.


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