Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy
| Autor: | Yvette Y Spano, Abigail Lara, Diane Hebblewaite, Lowrey Rhodes, Lourdes Nieves-Duran, Brigitte E Sanders-Beer, Dawn Golighty, Keith G. Mansfield |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
lcsh:Immunologic diseases. Allergy
medicine.medical_specialty business.industry Nephrosis Research Stavudine medicine.disease Emtricitabine Gastroenterology Nephropathy Internal medicine Virology Immunology medicine Molecular Medicine Pharmacology (medical) lcsh:RC581-607 business Viral load Blood urea nitrogen Immunodeficiency Hypophosphatemia medicine.drug |
| Zdroj: | AIDS Research and Therapy AIDS Research and Therapy, Vol 8, Iss 1, p 3 (2011) |
| ISSN: | 1742-6405 |
| DOI: | 10.1186/1742-6405-8-3 |
| Popis: | Background In many preclinical AIDS research studies, antiretroviral therapy (ART) is administered to experimentally simian immunodeficiency (SIV)-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r)-(phosphonomethoxy) propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily) can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily) starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine; emtricitabine) and stavudine (d4T). Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals) and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals). While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN) and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies. |
| Databáze: | OpenAIRE |
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