To provide updated estimates of the prevalence and clinical impact of human immunodeficiency virus−associated sensory neuropathy (HIV-SN) and neuropathic pain due to HIV-SN in the combination antiretroviral therapy (CART) era.
Design
Prospective, cross-sectional analysis. Clinical correlates for HIV-SN and neuropathic pain, including age, exposure to CART, CD4 levels, plasma viral load, hepatitis C virus infection, and alcohol use disorders, were evaluated in univariate and multivariate models.
Setting
Six US academic medical centers.
Patients
One thousand five hundred thirty-nine HIV-infected individuals enrolled in the CNS (Central Nervous System) HIV Anti-Retroviral Therapy Effects Research study.
Main Outcome Measures
The presence of HIV-SN, defined by 1 or more clinical signs (diminished vibration or sharp sensation in the legs and feet; reduced ankle reflexes) in a distal, symmetrical pattern. Neuropathic pain was defined as aching, stabbing, or burning in a similar distribution. The effect on quality of life was assessed with the Medical Outcomes Study HIV Health Survey.
Results
We found HIV-SN in 881 participants. Of these, 38.0% reported neuropathic pain. Neuropathic pain was significantly associated with disability in daily activities, unemployment, and reduced quality of life. Risk factors for HIV-SN after adjustment were advancing age (odds ratio, 2.1 [95% confidence interval, 1.8-2.5] per 10 years), lower CD4 nadir (1.2 [1.1-1.2] per 100-cell decrease), current CART use (1.6 [1.3-2.8]), and past “D-drug” use (specific dideoxynucleoside analogue antiretrovirals) (2.0 [1.3-2.6]). Risk factors for neuropathic pain were past D-drug use and higher CD4 nadir.
Conclusions
Neuropathic pain and HIV-SN remain prevalent, causing substantial disability and reduced quality of life even with successful CART. The clinical correlates of HIV-SN have changed with the evolution of treatment. These findings argue for redoubled efforts to determine HIV-SN pathogenesis and the development of symptomatic and neuroregenerative therapies.
Optimal antiretroviral therapy (ART) effectiveness depends on medication adherence, which is a complex behavior with many contributing factors, including neurocognitive function. Pharmacy refill records offer a promising and practical tool to assess adherence.A substudy of the CHARTER (CNS HIV Anti-Retroviral Therapy Effects Research) study was conducted at the Johns Hopkins University (JHU) and the University of Washington. Pharmacy refill records were the primary method to measure ART adherence, indexed to a "sentinel" drug with the highest central nervous system penetration-effectiveness score. Standardized neuromedical, neuropsychological, psychiatric, and substance use assessments were performed at enrollment and at 6 months. Regression models were used to determine factors associated with adherence and relationships between adherence and changes in plasma and cerebrospinal fluid HIV RNA concentrations between visits.Among 80 (33 at JHU and 47 at University of Washington) participants, the mean adherence score was 86.4%, with no difference between sites. In the final multivariable model, better neurocognitive function was associated with better adherence, especially among participants who were at JHU, male, and HIV infected for a longer period of time. Worse performance in working memory tests was associated with worse adherence. Better adherence predicted greater decreases in cerebrospinal fluid HIV RNA between visits.Poorer global neurocognitive functioning and deficits in working memory were associated with lower adherence defined by a pharmacy refill record measure, suggesting that assessments of cognitive function, and working memory in particular, may identify patients at risk for poor ART adherence who would benefit from adherence support.
This book took shape in ways that made it an unusually personal project, a work of scholarship tied to my everyday life more intimately than ever before.I would not have dared to make the book as close to me as it is without the support of an extraordinary network of colleagues, students, friends, and family who believed in me, in the project, and in horror studies as the connective tissue between the two.Given the blurring between my personal and professional lives that characterized the creation of this book from start to finish, I cannot hope to thank everyone who contributed to its coming into being; each one of you has my deepest gratitude,
Abstract Objective Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long‐term use in highly active ARV therapy. Methods We evaluated current and past exposure to PIs as a risk factor for DSPN in 1,159 HIV‐infected individuals enrolled in a large, prospective, observational, multicenter study. Signs of DSPN were ascertained by neurological examination. Subjects were grouped into categories according to past and current exposure to any ARV and to PIs. We included disease indicators such as nadir CD4, plasma viral load, and duration of HIV infection, as well as advancing age and exposure to dideoxynucleoside ARVs in multivariate models. Results In univariate analyses, both past and current PI exposure significantly increased the risk for DSPN. However, after adjusting for previously validated concomitant risk factors in multivariate models, none of the PI exposure groups was more likely to have DSPN than ARV naive subjects. A secondary evaluation of duration of PI use and exposure to individual PI drugs was similarly nonsignificant in multivariate models, except for small effects of amprenavir and lopinavir. Interpretation Evaluation of concomitant risks for HIV DSPN suggests that the independent risk attributable to PIs, if any, is small. This risk must be weighed against the important role of PIs in modern ARV therapy regimens. Ann Neurol 2008;64:566–572
