ART effective in treating HIV-related motor neuron disease

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Antiretroviral therapy is effective for treatment of HIV-related motor neuron disease (MND), according to a small US study.

The study was led by researchers from the National Institute of Neurological Diseases and Stroke, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, National Neurological AIDS Bank and department of neurology, University of California – Los Angeles. The small study, included 5 patients with HIV infection who developed signs that closely resembled amyotrophic lateral sclerosis (ALS).

Of the 5 patients treated, ALS-like symptoms reversed completely in 3 and progression was slowed in the other 2. All patients demonstrated both upper and lower motor neuron involvement that was observed to be consistent through independently performed serial electromyogram (EMG) and nerve conduction studies.

An accompanying editorial by Dr Joseph R Berger, of the University of Pennsylvania and Dr Christopher Power, of the University of Alberta in Canada, noted that coexistent cases of ALS and overlapping HIV infections were first reported in 1981, although over subsequent years, these cases appeared to remit or at least stabilise.

Seven cases of ALS-type symptoms were effectively resolved by antiretroviral therapy in seropositive HIV patients in 2001. The suggestion at the time was that the mechanism of retroviruses provided the perfect vehicle for transmission of ALS into the DNA. This HERV-K variation appears to be symptomatically identical to idiopathic ALS, with the important exception that it appears to be largely treatable if caught early.

Based on this history, the investigators monitored HERV-K levels in all 5 patients studied. Antiretroviral therapies may produce varied responses in different cell types, and some of the agents have reduced uptake by the central nervous system (CNS), although the degrees of variation are not clearly measurable. One patient treated with a dosage sufficient to manage viral load still demonstrated HERV-K activity, and so the dose was enhanced, which resulted in stabilizing the HERV-K levels. Three of the patients who received antiretroviral treatment within 6 months of the appearance of ALS-like symptoms showed significant improvement in those symptoms, suggesting that up to 6 months is the optimal treatment window when given in higher doses that penetrate the CNS.

As it appeared that HERV-K levels, while reduced in all patients, did not fully arrest after treatment, the investigators further recommended monitoring HERV-K levels to prevent re-elevations from occurring over time.

Although this initial study was small, Berger and Power speculate that it points to acquired HERV-K activation as a potential mechanism for HIV-associated ALS that may be generalisable to other sporadic forms of ALS. If this turns out to be the case, they suggest, then by extension, HERV-K expression in people without HIV infection suggests justification for antiretroviral therapy at similar doses to reduce HIV-ALS-type symptoms.

Abstract
Objective: To determine whether there is activation of human endogenous retrovirus K (HERV-K) in amyotrophic lateral sclerosis in HIV infection and whether it might respond to treatment with antiretroviral drugs.
Methods: In this case series, we present 5 patients with HIV infection who subsequently developed motor neuron disease involving both upper and lower motor neurons. We monitored HERV-K levels in plasma of 4 of these patients.
Results: Three patients who received antiretroviral therapy had reversal of symptoms within 6 months of onset of neurologic symptoms and the other 2 had slow neurologic progression over several years. Three patients in whom the levels were measured at onset of neurologic symptoms showed elevated HERV-K levels that responded to optimization of antiretroviral therapy for CNS penetration.
Conclusions: Thus, motor neuron disease in individuals with HIV infection may a treatable entity, but early treatment with CNS-penetrating antiretroviral therapy may be necessary. Monitoring of HERV-K levels may help guide treatment.

Authors
Bowen LN, Tyagi R, Li W, Alfahad T, Smith B, Wright M, Singer EJ, Nath A

Infectious Disease Advisor report
Neurology abstract
Neurology editorial


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