HIV-associated motor neuron disease: HERV-K activation and response to antiretroviral therapy.
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.
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Lauren N
LN
Bowen
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Richa
R
Tyagi
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Wenxue
W
Li
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Tariq
T
Alfahad
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Bryan
B
Smith
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Mary
M
Wright
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles.
Elyse J
EJ
Singer
From the Section of Infections of the Nervous System, National Institute of Neurological Diseases and Stroke (L.N.B., R.T., W.L., T.A., B.S., A.N.), and National Institute of Allergy and Infectious Diseases (M.W.), NIH, Bethesda, MD; and National Neurological AIDS Bank and Department of Neurology (E.J.S.), University of California, Los Angeles. natha@ninds.nih.gov.
Avindra
A
Nath
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D020077:Endogenous Retroviruses / Q000302:isolation & purification*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000209:etiology* / Q000821:virology
Curr HIV Res. 2012 Dec;10(8):694-9
22998474
J Neurovirol. 2016 Jun;22(3):349-57
26572786
J Neurovirol. 2000 Apr;6(2):145-55
10822328
Arch Neurol. 2008 Jan;65(1):65-70
18195140
Clin Neuropathol. 1998 May-Jun;17(3):131-5
9625304
J Chemother. 2004 Feb;16(1):98-101
15078007
AIDS Res Hum Retroviruses. 2007 Jan;23(1):116-22
17263641
Neurology. 1994 Nov;44(11):2159-64
7969977
Rev Neurol. 1997 Apr;25(140):552-4
9172917
AIDS. 2000 Dec 1;14(17):2709-13
11125889
Antivir Ther. 2012;17(7):1233-42
23018140
Neurology. 2005 Feb 8;64(3):454-8
15699374
Ann Neurol. 2011 Jan;69(1):141-51
21280084
Neurol Neuroimmunol Neuroinflamm. 2015 May 14;2(4):e113
26015990
Neurology. 2007 May 29;68(22):1944-6
17536052
Top Antivir Med. 2011 Nov;19(4):137-42
22156215
J Virol. 2014 Aug;88(16):8924-35
24872592
Neurology. 1990 Mar;40(3 Pt 1):544-6
2156185
BMJ Case Rep. 2012 Dec 06;2012:null
23220836
Neurol Int. 2015 Sep 24;7(2):5885
26487927
Amyotroph Lateral Scler. 2010;11(1-2):91-6
19322704
J Neurol Sci. 1999 Oct 31;169(1-2):13-21
10540002
J Exp Med. 1975 Aug 1;142(2):483-94
49390
Sci Transl Med. 2015 Sep 30;7(307):307ra153
26424568
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13588-93
23898208
Viruses. 2015 Mar 04;7(3):939-68
25746218
Retrovirology. 2011 Nov 08;8:90
22067224
J Neurol. 2000 Sep;247(9):718-9
11081817
N Engl J Med. 1985 Apr 4;312(14):874-9
3974673
Antiviral Res. 2013 Aug;99(2):180-7
23707220
Neurology. 2008 Jan 22;70(4):278-83
18209202
AIDS. 2015 Apr 24;29(7):755-66
25985398