HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank.
OBJECTIVE
To examine distal sensory polyneuropathy (DSP) in a highly active antiretroviral therapy era, human immunodeficiency virus (HIV)-infected cohort, to determine whether clinical manifestations are affected by demographic or other clinical variables.


METHODS
One hundred eighty-seven patients with HIV infection enrolled in the Manhattan HIV Brain Bank underwent baseline neurologic evaluations between January 29, 1999, and June 17, 2002. Distal sensory polyneuropathy was diagnosed if patients displayed abnormalities in 2 or more of the following: ankle reflexes or vibratory or pinprick perception. Patients were classified as symptomatic if they described pain, paresthesia, or numbness. Nonneurologic information was obtained by interview, laboratory testing, and medical chart review. Psychiatric and substance use disorders were elucidated by semistructured interview. In 36 patients, morphometric analysis was performed on autopsy-derived sural nerves.


RESULTS
Of 187 patients, 99 (53%) had DSP. Patients with neuropathy were older than those without (mean +/- SD age, 45.3 +/- 0.7 vs 41.2 +/- 0.8 years, P <.001), and DSP was significantly more common in men (58% [83/99]) than in women (37% [16/99]) (P =.02). The presence of neuropathy was not correlated with plasma viral load, decreased CD4 cell counts, or neurotoxic antiretroviral therapy. Twenty-six of 99 patients with DSP were asymptomatic. Asymptomatic neuropathy was correlated with histories of opiate and sedative abuse and dependence. Symptomatic DSP correlated with ethanol and hallucinogen syndromes, but not neurotoxic therapy. Sural nerve morphometric findings did not distinguish between patients with substance use syndromes and those without.


CONCLUSIONS
In contrast to populations before the era of highly active antiretroviral therapy, DSP in the Manhattan HIV Brain Bank cohort is not associated with increased viral load or decreased CD4 cell counts in this cross-sectional analysis. Symptoms in DSP are associated with substance use disorders, but no difference in morphologic structure is seen in nerves of patients with HIV infection with and without substance use histories. Previously reported virologic and immunologic underpinnings of DSP may be affected by highly active antiretroviral therapy. Furthermore, symptoms of DSP in substance users may be altered by central mechanisms of increased or decreased tolerance to sensory disturbance.
Morgello
Susan
S
Department of Pathology, The Mount Sinai Medical Center, New York, NY 10029, USA. susan.morgello@mssm.edu
Estanislao
Lydia
L
Simpson
David
D
Geraci
Anthony
A
DiRocco
Alessandro
A
Gerits
Pieter
P
Ryan
Elizabeth
E
Yakoushina
Tatiana
T
Khan
Shafat
S
Mahboob
Rashid
R
Naseer
Mubasher
M
Dorfman
David
D
Sharp
Victoria
V
D000328:Adult; D000842:Ankle / Q000294:innervation*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009443:Neuritis / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D009460:Neurologic Examination; D011115:Polyneuropathies / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D019966:Substance-Related Disorders / Q000150:complications / Q000453:epidemiology; D013497:Sural Nerve / Q000473:pathology