title: Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.
abstract: Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.
authors.affiliation: From the Departments of Molecular and Comparative Pathobiology (JLD, LMM, SEQ, VAL, RJA, JLM), Pathology (JLM), and Neurology (PH, GJE, JLM), Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Dorsey
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mangus
authors.forename: Peter
authors.initials: P
authors.lastname: Hauer
authors.forename: Gigi J
authors.initials: GJ
authors.lastname: Ebenezer
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Queen
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Laast
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008254:Macaca nemestrina; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000209:etiology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D012867:Skin / Q000294:innervation / Q000473:pathology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D043222:Ubiquitin Thiolesterase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C482860:UCHL1 protein, human