Prevalence and risk factors for patient-reported joint pain among patients with HIV/Hepatitis C coinfection, Hepatitis C monoinfection, and HIV monoinfection

We performed a cross-sectional study among patients with HIV/chronic HCV coinfection, chronic HCV monoinfection, and HIV monoinfection. Consecutive patients with chronic HCV and/or HIV infections were recruited in hepatology and infectious disease clinics at three tertiary care medical centers within Philadelphia (Penn Presbyterian Medical Center [PPMC], Philadelphia Veterans Affairs Medical Center [PVAMC], and the Hospital of the University of Pennsylvania [HUP]). The PPMC infectious disease outpatient practice specializes in viral hepatitis care; hepatologists and infectious disease physicians see patients concurrently in the HUP viral hepatitis clinic; and the PVAMC outpatient infectious disease and hepatology clinics are located within the same practice space. Patients were enrolled between November 2008 and March 2012.

Participants were eligible for inclusion if they were between 18 and 80 years of age and had documentation of HIV (HIV antibody- or RNA-positive) and/or chronic HCV infection (HCV RNA-positive) in their medical record. Exclusion criteria included the inability to either speak or understand English or to provide informed consent.

Participants were asked to complete an interviewer-administered questionnaire that ascertained the presence or absence of patient-reported joint pain over the one week prior to the study visit, the duration of joint pain, the joints affected, and previous diagnoses of joint disorders or arthritis. Among patients reporting joint pain, an interviewer administered the Multi-Dimensional Health Assessment Questionnaire (MD-HAQ, version R780-NP2) [16] given the highly varied reading skills and medical literacy in the patient population surveyed. Interviews were standardized among the four questionnaire administrators (WGP, LM, SB, and AO). The MD-HAQ includes a physical function score (range, 0 to 10), emotional function score (0 to 9.9), a pain score (range, 0 to 10), global health assessment (range, 0 to 10), fatigue scale (range, 0 to 10), ratings of painful joints, responses to a review of systems, and basic demographics (e.g. age, sex, height, weight, education, employment status and occupation). The MD-HAQ scores for physical function, pain, and global health status can be combined into a composite index known as the Routine Assessment of Patient Index Data (RAPID3; range, 0 to 30). In rheumatoid arthritis, a RAPID3 score of > 12 (on a scale from 0–30) indicates high disease activity, a score of 6.01-12 suggests moderate disease activity, a score of 3.01-6 suggests lower disease activity, and scores ≤ 3 indicate disease remission [17]. The MD-HAQ also includes three questions on “emotional function” (depression, anxiety, sleep disturbance), each ranging from 0 to 3.3 in 1.1 increments. These three scores were summed to result in an “emotional function” score ranging from 0–9.9. The MD-HAQ includes a review of systems, including symptoms such as dry mouth, dry eyes, numbness and tingling in the extremities, myalgias, and morning stiffness (a total of 60 symptoms are included in the review of systems) and a visual analog scale for fatigue. The MD-HAQ and RAPID3 have been validated in patients with rheumatoid arthritis and have previously been used in rheumatologic epidemiological studies [18-20]. Additionally, the MDHAQ has been used in clinical practice to evaluate many different diseases, including osteoarthritis and fibromyalgia [21,22].

Medical records were also reviewed to abstract age at study visit, sex, race, height and body weight, analgesic medication use (e.g., use of narcotic analgesics, non-steroidal anti-inflammatory drugs, acetaminophen, or gabapentin), medical comorbidities (i.e., diabetes mellitus, hypertension, congestive heart failure, coronary artery disease, hyperlipidemia, obstructive sleep apnea, chronic kidney disease, psoriasis, inflammatory bowel disease, lymphoma, thyroid disease, history of arthritis, anxiety disorder, depression), HIV-related data (CD4 cell count, HIV RNA level, use of antiretroviral therapy), HCV-related data (HCV genotype, HCV RNA level, current or prior interferon-based HCV therapy; hepatic decompensation diagnoses [ascites, spontaneous bacterial peritonitis, esophageal variceal hemorrhage, hepatic encephalopathy]; hepatocellular carcinoma), relevant social history (history of smoking, alcohol use, intravenous drug use, homelessness, incarceration, blood transfusion), and most recently recorded laboratory results of total bilirubin, asparate aminotransferase (AST), alanine aminotransferase (ALT), albumin, international normalized ratio (INR), white blood cell count, hemoglobin, and platelet count.

The prevalence of joint pain was determined and expressed as a point estimate (percent) and 95% confidence interval (CI) within each group. Descriptive statistics were used to compare characteristics between groups (HIV/HCV-coinfected, HCV-monoinfected, and HIV-monoinfected). Differences between groups were determined using Chi-square or Fisher’s exact tests, when appropriate, for categorical data, and Wilcoxon rank-sum tests for continuous data. Logistic regression was used to determine adjusted odds ratios (aORs) with 95% CIs of joint pain associated with risk factors of interest among chronic HCV-infected (i.e., HIV/HCV-coinfected and HCV-monoinfected) and HIV-infected (i.e., HIV/HCV-coinfected and HIV-monoinfected) patients. Variables evaluated as risk factors for joint pain included age, sex, race, history of arthritis, history of anxiety disorder or depression, obesity (body mass index [BMI] > 30 kg/m²), AST, ALT, current HCV therapy, use of analgesic medications, HCV genotype (in chronic HCV-infected patients only), and CD4 cell count (in HIV-infected patients only). Since HCV treatment has been associated with arthralgias, we performed a sensitivity analysis in which we excluded patients currently utilizing this therapy and repeated the analyses above.

This study was approved by the Institutional Review Boards of the University of Pennsylvania and PVAMC. Written informed consent was obtained from all patients participating in the study.