Antiretroviral toxic neuropathy

Antiretroviral toxic neuropathy Any stage Subacute rarely acute with lactic acidosis Distal sensory loss and neuropathic pain Toxic neuropathy mitochondrial damage... 

The phenotype and clinical presentation of antiretroviral toxic neuropathy (ATN) are similar to those of HIV-associated DSP. However, ATN is more likely to be painful, and has an abrupt onset and rapid progression. The main diagnostic clue is the temporal relationship of peripheral neuropathy to the start of NRTI therapy and stabilization, or at least the partial resolution when therapy is interrupted (Moyle and Sadler 1998). ATN most often develops after a mean of 16 to 20 weeks of treatment, unless there are other conditions that lower the threshold. Symptomatic improvement over weeks to months has been reported in two thirds of patients after discontinuation of the offending drug, but may be preceded by an initial period of worsening symptoms, also known as coasting (Berger et al. 1993). Despite the improvement, most patients do not return to a completely asymptomatic state (Hoke and Comblath 2004). 

Herzberg U, Sagen J (2001) Peripheral nerve exposure to HIV viral envelope protein gpl20 induces neuropathic pain and spinal gliosis. J Neuroimmunol 116(l) 29-39 Herzmann C, Johnson MA et al (2005) Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials 6(6) 344-350... 

Keswani SC, Chander B et al (2003a) FK506 is neuroprotective in a model of antiretroviral toxic neuropathy. Ann Neurol 53(l) 57-64... 

Youle M, Oslo M (2007) A double-blind, parallel-group, placebo-controUed, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med 8(4) 241-250... 

Combination therapy - For toxicities likely to be associated with zalcitabine (eg, peripheral neuropathy, severe oral ulcers, pancreatitis, elevated liver function tests, especially in patients with chronic hepatitis B see Warnings and Precautions), interrupt or reduce dose. For severe toxicities or those persisting after dose reduction, interrupt zalcitabine therapy. For recipients of combination therapy with zalcitabine and other antiretrovirals, base dose adjustments or interruption for either drug on the known toxicity profile of the individual drugs. 

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. 

Intravenous foscarnet 90 mg/kg every 12 hours and oral zalcitabine 750 micrograms every 8 hours were given to 12 HIV-positive subjects for 2 days. There were no clinically significant alterations in the pharmacokinetics of either drug. However, the manufacturers of zalcitabine suggested that the concurrent use of zalcitabine and foscarnet should be well monitored, because foscarnet may possibly decrease the renal elearanee of the zalcitabine, thereby increasing its serum levels and its toxicity, particularly peripheral neuropathy. The antiretroviral effects of foscarnet and zalcitabine were synergistic. ... 

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