Toxicity lipodystrophy

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

In combination with other antiretroviral agents, stavudine has caused fatal lactic acidosis in some patients. It is also associated with motor weakness in which case it should be discontinued. Peripheral neuropathy is the most common toxicity associated with stavudine, which is more prevalent at high doses (4mg/kg per day). Neuropathy in these patients generally is associated with numbness, tingling or pain in feet or hands. Patients treated with the combination of stavudine and didanosine may also exhibit liver function abnormalities (hepatic steatosis) and pancreatitis. It may also be associated with the etiology of HIV lipodystrophy syndrome. 

Brinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 1999 354 1112-5. 

Unproven clinical benefit among patients with relatively intact immune system Concern with known short-term toxicities and unknown long-term complications High levels of triglycerides and lipodystrophy... 

The most common adverse effect with stavudine is peripheral neuropathy which occurs in -12% of patients. Combining stavudine with zidovudine leads to increased risk and severity of peripheral neuropathy and potentially fatal pancreatitis, and these drugs shorrld not be used together under most circumstances. Lactic acidosis and hepatic steatosis also have been seen and are more common with stavudine than with zidovudine or abacavir. Of aU the nucleoside analogs, stavudine is most strongly linked to the HIV lipodystrophy syndrome, perhaps due to toxic effects on adipocytes. 

D. Other serious toxicities that develop after chronic use of many of these agents include bone marrow depression, diabetes mellitus, hepatotoxicity, lactic acidosis, lipodystrophy, lipoatrophy, pancreatitis, peripheral neuropathy, renal failure, and seizures. 

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