Monica M Diaz1, John R Keltner2,3, Alan N Simmons2,3, Donald Franklin3, Raeanne C Moore3, David Clifford4, Ann C Collier5, Benjamin B Gelman6, Ph D Christina Marra5, J Allen McCutchan7, Susan Morgello8, Ned Sacktor9, Brookie Best10, Christine Fennema Notestine3, Sara Gianella Weibel7, Igor Grant3, Thomas D Marcotte3, Florin Vaida11, Scott Letendre3,7, Robert Heaton3, Ronald J Ellis1,3. 1. Department of Neurosciences, University of California, San Diego, La Jolla, California. 2. Center of Excellence in Stress and Mental Health, San Diego Veterans Health System, San Diego, California. 3. Department of Psychiatry, University of California, San Diego, La Jolla, California. 4. Washington University, St. Louis, Missouri. 5. University of Washington, Seattle, Washington. 6. University of Texas Medical Branch, Galveston, Texas. 7. Department of Medicine, University of California, San Diego, La Jolla, California. 8. Icahn School of Medicine at Mount Sinai, New York, New York. 9. Johns Hopkins University, Baltimore, Maryland. 10. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California. 11. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, California, USA.
Abstract
OBJECTIVE: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.
OBJECTIVE: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. METHODS: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. RESULTS: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]). CONCLUSIONS: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.
Authors: Corinne G Jolivalt; Katie E Frizzi; May Madi Han; Andre J Mota; Lucie S Guernsey; Lakshmi P Kotra; Paul Fernyhough; Nigel A Calcutt Journal: J Pharmacol Exp Ther Date: 2020-04-23 Impact factor: 4.030
Authors: Mary Lou A Galantino; David M Kietrys; James Scott Parrott; Maureen E Stevens; Anne Marie Stevens; David V Condoluci Journal: Phys Ther Date: 2014-05-22
Authors: John R Keltner; Colm G Connolly; Florin Vaida; Mark Jenkinson; Christine Fennema-Notestine; Sarah Archibald; Cherine Akkari; Alexandra Schlein; Jisu Lee; Dongzhe Wang; Sung Kim; Han Li; Austin Rennels; David J Miller; George Kesidis; Donald R Franklin; Chelsea Sanders; Stephanie Corkran; Igor Grant; Gregory G Brown; J Hampton Atkinson; Ronald J Ellis Journal: Pain Med Date: 2017-03-01 Impact factor: 3.750
Authors: John R Keltner; Christine Fennema-Notestine; Florin Vaida; Dongzhe Wang; Donald R Franklin; Robert H Dworkin; Chelsea Sanders; J Allen McCutchan; Sarah L Archibald; David J Miller; George Kesidis; Clint Cushman; Sung Min Kim; Ian Abramson; Michael J Taylor; Rebecca J Theilmann; Michelle D Julaton; Randy J Notestine; Stephanie Corkran; Mariana Cherner; Nichole A Duarte; Terry Alexander; Jessica Robinson-Papp; Benjamin B Gelman; David M Simpson; Ann C Collier; Christina M Marra; Susan Morgello; Greg Brown; Igor Grant; J Hampton Atkinson; Terry L Jernigan; Ronald J Ellis Journal: J Neurovirol Date: 2014-02-19 Impact factor: 2.643