John Koeppe

Ongoing Pain Despite Aggressive Opioid Pain Management Among Persons With HIV

BackgroundChronic pain is a common problem among persons living with HIV and opioids are frequently used in its treatment. However, data on the variables associated with opioids use and the efficacy of this practice are lacking. MethodsWe performed a cross-sectional cohort study of self-reported pain during the year 2005 in our clinic. Patients were grouped into 3 cohorts: those receiving daily opioid therapy for chronic pain (cohort 1, n=115), those with a chronic pain diagnosis but not on daily opioid therapy (cohort 2, n=209), and those without a chronic pain diagnosis (cohort 3, n=796). ResultsIn multivariate analysis comparing cohorts 1 and 2, patients in cohort 1 were significantly more likely to be on a benzodiazepine or gamma-aminobutyric receptor agonist [odds ratio (OR)=15.2], have injection drug use as a HIV risk factor (OR=4.27), lack private insurance (OR=3.51), have been abused (OR=3.08), have a history of AIDS (OR=2.21), and be seen more frequently (OR=1.18). Patients in cohort 1 reported significantly more pain [mean pain scores (0 to 10): 4.3 cohort 1; 1.9 cohort 2; 0.7 cohort 3], and were more likely to have pain that was of moderate or greater severity (58.6% cohort 1; 15.5% cohort 2; 4.9% cohort 3). ConclusionsPsychosocial variables and a history of AIDS were associated with opioid use in our clinic. Persons on opioids continued to experience significantly more pain than other patients in our clinic.

Contribution of Intestinal Barrier Damage, Microbial Translocation and HIV-1 Infection Status to an Inflammaging Signature

Background Systemic inflammation is a characteristic of both HIV-1 infection and aging (“inflammaging”). Intestinal epithelial barrier damage (IEBD) and microbial translocation (MT) contribute to HIV-associated inflammation, but their impact on inflammaging remains unclear. Methods Plasma biomarkers for IEBD (iFABP), MT (LPS, sCD14), T-cell activation (sCD27), and inflammation (hsCRP, IL-6) were measured in 88 HIV-1 uninfected (HIVneg) and 83 treated, HIV-1-infected (HIVpos) adults from 20–100 years old. Results Age positively correlated with iFABP (r = 0.284, p = 0.008), sCD14 (r = 0.646, p = <0.0001) and LPS (r = 0.421, p = 0.0002) levels in HIVneg but not HIVpos subjects. Age also correlated with sCD27, hsCRP, and IL-6 levels regardless of HIV status. Middle-aged HIVpos subjects had elevated plasma biomarker levels similar to or greater than those of elderly HIVneg subjects with the exception of sCD14. Clustering analysis described an inflammaging phenotype (IP) based on iFABP, sCD14, sCD27, and hsCRP levels in HIVneg subjects over 60 years of age. The IP in HIVneg subjects was used to develop a classification model that was applied to HIVpos subjects to determine whether HIVpos subjects under 60 years of age were IP+. HIVpos IP+ subjects were similar in age to IP- subjects but had a greater risk of cardiovascular disease (CVD) based on Framingham risk score (p =  0.01). Conclusions We describe a novel IP that incorporates biomarkers of IEBD, MT, immune activation as well as inflammation. Application of this novel IP in HIV-infected subjects identified a group at higher risk of CVD.

HIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia.

Objectives:To determine whether increased sequence variation occurs in regions of endogenous HIV-1 targeted by HIV-1-specific CD4+ T cells. The presence of increased variation would be suggestive of immune evasion by HIV-1. Design:We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-γ-secreting CD4+ T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation. Methods:CD8- depleted IFNγ enzyme-linked immunospot assays were used to identify regions of HIV-1 Gag recognized by CD4+ T cells. Reverse transcriptase polymerase chain reaction and TA cloning were used to sequence endogenous plasma HIV-1 virus and identify variants. Results:CD4+ T-cell epitopes in Gag p17 and p24 were identified in 5 individuals, and concurrent sequence information on endogenous HIV-1 was obtained in 4 of these individuals. Endogenous plasma HIV-1 RNA sequencing revealed no intrapatient amino acid sequence variation through identified epitopes. Conclusions:In these chronically infected viremic subjects, circulating IFNγ-secreting CD4+ T-cell responses were directed against epitope sequences found in the predominant strain of endogenous circulating plasma HIV-1, suggesting that escape from CD4+ T-cell responses is not a common process in vivo.

Variables associated with decreasing pain among persons living with human immunodeficiency virus: a longitudinal follow-up study.

BackgroundPain is common among persons with human immunodeficiency virus (HIV); however, there are minimal data on its natural history, or the long-term efficacy of analgesic therapies. MethodsWe performed an observational study between 2001 and 2009. Pain was defined on a 0 to 10 scale; 0=no pain; 10=worst pain possible. Patients were included if they were HIV positive, had a chronic pain diagnosis, a median pain score during the first year of observation of ≥1.0, ≥2 years of follow-up, and ≥3 recorded pain scores. Two models were used to describe decreasing pain. Model 1 defined decreasing pain as a negative slope to the best fit line through all recorded pain scores. Model 2 defined decreasing pain as a median pain score of zero during the last year of follow-up. ResultsUsing model 1, decreasing pain was negatively associated with a history of being abused (odds ratio=0.29) and positively associated with peripheral neuropathy (3.54). Using model 2, decreasing pain was positively associated with highly active antiretroviral therapy (3.71) and negatively associated with opioid analgesic use (0.24). ConclusionsWe found social and HIV-related variables associated with decreasing pain. We failed to show a positive association between analgesic use and decreasing pain.

Factors associated with initiation of prolonged analgesic use among patients in the hiv outpatient study (HOPS)

BackgroundAnalgesic use is common but remains poorly described among human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy era. MethodsWe studied HIV Outpatient Study participants during 1996 to 2008. We used Cox proportional hazards regression to assess variables associated with initiation of prolonged analgesia (≥90 consecutive days of analgesics); logistic regression to explore variables associated with initiation of prolonged opioid analgesia among those taking any prolonged analgesia; and linear regression to determine temporal trends in prolonged analgesia. ResultsAmong 4180 patients, 931 (22%) initiated prolonged analgesia. Factors independently associated (P<0.05) with prolonged analgesia included: age above 40 years (hazard ratio=1.20), female sex (1.43), injection drug use as an HIV risk factor (1.33), public healthcare payer (1.88), nadir CD4+ less than 200 cells/mm3 (1.29), tobacco use (1.43), prior opportunistic infection(s) (1.25), antidepressant use (1.76), and anxiolytic use (1.51). Independent correlates of prolonged opioid analgesia were white race (odds ratio=1.64), baseline CD4+ less than 350 cells/mm3 (1.88), and anxiolytic use (1.87). Prolonged analgesia ranged from 11% to 15% each year. ConclusionsIn the highly active antiretroviral therapy era, up to 15% of HIV Outpatient Study patients used prolonged analgesic therapy each year. Variables associated with the initiation of prolonged analgesia included HIV and non-HIV-related factors.

Association between opioid use and health care utilization as measured by emergency room visits and hospitalizations among persons living with HIV.

Background:Epidemiologic studies in the non–human immunodeficiency virus (HIV) positive population have shown greater health care utilization among persons with chronic non-cancer pain on opioid therapy. However, we are not aware of any similar data in the HIV positive population. Methods:We evaluated health care utilization, as measured by emergency room (ER) visits and hospitalizations, among persons with HIV and chronic pain seen at an academic medical center, during the calendar year 2005. We compared these outcomes between patients on chronic opioid therapy with those not on opioids. Results:In univariate models chronic opioid therapy was associated with both ER visits and hospitalization: ER visits odds ratio (OR)=2.18 (95% confidence interval [CI], 1.30-3.66), hospitalization OR=1.90 (95% CI, 1.03-3.51). After multivariate analyses only nonsignificant trends remain: ER visits OR=1.71 (95% CI, 0.95-3.08); hospitalization OR=1.28 (95% CI, 0.66-2.49). Conclusions:In our study HIV positive individuals with chronic pain were more likely to be seen in the ER and be hospitalized if they were on opioids. However, after controlling for other variables, the association with opioids no longer remained significant.

Apparent Resolution of Type 2 Diabetes Mellitus after Initiation of Potent Antiretroviral Therapy in a Man from Africa with HIV Infection

We describe a 52-year-old African man with human immunodeficiency virus infection and type 2 diabetes mellitus whose diabetes resolved as viral replication was suppressed with protease inhibitor-based antiretroviral therapy. This case suggests that human immunodeficiency virus infection itself can precipitate overt diabetes mellitus.

Ochrobactrum anthropi septic arthritis: case report and implications in orthopedic infections

Ochrobactrum anthropi is a rare cause of orthopedic infections. We report the second case of Ochrobactrum anthropi septic arthritis in the literature. Our case highlights the ability of Ochrobactrum anthropi to cause septic arthritis and its relevance in the field of orthopedic infections.

Mycobacterium avium complex cervical lymphadenitis in an immunocompetent adult.

ABSTRACT Nontuberculosis mycobacterial cervical lymphadenitis is a relatively common disease in immunocompetent children but a rare disease in immunocompetent adults. We report the diagnosis and treatment of Mycobacterium avium complex cervical lymphadenitis in an adult female. Our evaluation of immune competence, including gamma interferon (IFN-γ) and interleukin-12 (IL-12) signaling, found no evidence of deficiency.