title: Better Antiretroviral Central Nervous System Penetration is Not Associated with Reduced Chronic Pain in People Living with Human Immunodeficiency Virus.
abstract: OBJECTIVE
  To determine if better antiretroviral (ARV) central nervous system (CNS) penetration is associated with reduced rates of chronic pain in people living with HIV (PLWH).
  
  
  BACKGROUND
  Chronic pain remains prevalent in PLWH despite widespread ARV use. Mechanisms underlying this prevalence remain unknown, though neuroinflammation from persistent CNS HIV infection and maladaptive plastic changes in the CNS have been implicated. Here we hypothesize that better CNS ARV penetration, measured using the CNS Penetration-Effectiveness (CPE) score, would decrease rates of chronic pain.
  
  
  METHODS
  We interviewed 254 consecutive adults from an HIV clinic in Chiang Mai, Thailand. We collected data on demographics, HIV history, ARV use, and pain characteristics. Patients were evaluated for depression using a Thai two question Patient Health Questionnaire (PHQ-2). Modified CPE score was calculated using established methods and grouped a priori into "low CPE" (≤7, poor penetration) and "high CPE" (≥8, good penetration). CPE score was compared with chronic pain scores in SPSS using appropriate statistical tests. A relationship between CPE score and a positive depression screen was tested further using multivariable binary logistic models.
  
  
  RESULTS
  245 of 254 subjects were on ARVs. Complete ARV data was available for 235 patients. 137 of these 235 patients (58.3%) had a CPE score ≤7, and 98 (41.7%) had a score ≥8. 49 patients had chronic pain, and 9 had neuropathic pain. Low CPE score was not associated with chronic pain (p=0.64), neuropathic pain (p=0.56), or frequent pain (p=0.80), nor was it associated with the severity of reported "worst pain" or "average pain" in the last 24 hours (p=0.18 and 0.48, respectively).Post-hocanalysis revealed that higher CPE score was a significant independent risk factor for depression measured by a positive PHQ-2 screen [OR (95% CI) = 1.29 (1.04-1.61), p=0.02]. This relationship was mediated primarily by exposure to zidovudine.
  
  
  CONCLUSIONS
  CPE score is not associated with chronic pain in PLWH.Post-hocanalysis demonstrated that CPE score, and zidovudine exposure in particular, predicts a positive depression screen. Given the substantial morbidity associated with chronic pain and mood disorders in PLWH, additional studies to determine preventable and treatable factors are imperative.
authors.affiliation: Department of Neurology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Robbins
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Kanokporn
authors.initials: K
authors.lastname: Chaiklang
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
keywords: AIDS; HAART; HIV; antiretroviral agents; depression; pain management