Peripheral neuropathy in HIV disease: Lactate levels may help determine if nucleoside toxicity is a contributing factor
Paul Blanchard, HIV i-Base
With both HIV itself and antiretrovirals implicated in the development of HIV-related peripheral neuropathy it can be difficult to determine which may be the dominant aetiology in a particular individual. Given that nucleoside associated neuropathy may be related to nucleoside induced mitochondrial dysfunction, a marker of such dysfunction, blood lactate levels, might be useful in differentiating nucleoside induced from other neuropathies.
Bruce Brew and colleagues presented data on lactate levels in HIV neuropathy as a poster during the 8th Conference on Retroviruses and Opportunistic Infections (2001). It appears to be this data set, in an updated form, which has now been published as a research letter in the journal AIDS.
All outpatients at an Australian HIV medicine hospital department developing peripheral neuropathy were studied prospectively over one year and venous lactate levels and HIV viral load measured. Nucleoside neuropathy was diagnosed following exclusion of other likely causes and symptom improvement after cessation of the nucleoside. HIV neuropathy was diagnosed if clinical features were the same as for nucleoside neuropathy, except that patients were not taking didanosine, stavudine or zalcitabine (ddX nucleoside), and after exclusion of other likely causes. A control group consisted of patients without neuropathy, taking antiretroviral therapy (which may have included ddX) and with CD4 counts less than 200 cells/mL. The ability of raised serum lactate concentrations (>2.2 mmol/l) and detectable HIV viral load to discriminate between these groups was assessed using logistic regression. (See Table 1)
|ddX nucleosidewith neuropathy (n=20)||HIV with neuropathy (n=10)||ddX nucleoside with no neuropathy (n=20)||No ddX nucleoside with no neuropathy (n=23)|
|3.16 ± 0.81||1.8 ± 0.67||1.68 ± 0.4||1.54 ± 0.36|
|% lactate >2.2 mmol/l||90||10||15||0|
|HIV RNA (log copies/ml)||2.79 ± 0.58||3.95 ± 1.28||2.9 ± 0.61||2.83 ± 0.64|
|% less than 400 copies/ml||90||40||75||83|
Logistic regression determined that an elevated serum lactate was 90% sensitive and 90% specific in discriminating between ddX neuropathy and HIV neuropathy. The researchers concluding that “…elevated serum lactate concentrations can be useful in the diagnosis of nucleoside neuropathy and its distinction from (HIV related) distal sensory peripheral neuropathy (DSPN), whereas the plasma HIV viral load is not, and indeed 40% of DSPN patients had a plasma viral load below 400 copies/ml.”
Ref: Brew BJ, Tisch S, Law M. Lactate concentrations distinguish between nucleoside neuropathy and HIV neuropathy. AIDS 2003 May 2;17(7):1094-6.
The authors of this study comment that in all 20 ddX neuropathy patients the neuropathy was considered to be related to stavudine. They also note that in these 20 patients a switch to either zidovudine or abacavir led to improvement in the severity of the neuropathy and normalisation of the serum lactate. Interestingly chart review revealed that the patients who developed HIV neuropathy with viral loads <400 copies/ml had development and progression of their neuropathy in the context of suppressed viral loads.
Results from in vitro studies with HepG2-cells published by Walker et al in AIDS 2002 and shown at the 4th Lipodystrophy Workshop demonstrate that a raise of lactate and mitochondrial damage as assessed by the appearance of cyclooxygenase in the supernatant must not be closely associated. Clinically a switch of a d-drug to another a non-d-drug would be the consequence even in individuals with “HIV”-peripheral neuropathy, because of additive toxicity or virological failure.