During the study period, the assessment was completed by 764 eligible HIV-infected patients of whom 160 (21%) had HCV infection (see ). One patient receiving pegylated interferon therapy was excluded from the study. Completion rates were high with minimal missing data. Missing data rates for each symptom item were all <3%, with the highest rate for the nausea item (missing for 19/764, 2.5%). There were 28 patients who had missing data for the AUDIT-C (3.7%), and 44 patients who had missing data for any of the items for the EuroQOL (5.6%). The median age was 45 years old, 87% were men, the median current CD4+ T cell count was 393 cells/mm3, and the mean BMI was 26.6 kg/m2 (SD 5.0). At the time of the assessment, 172 patients (23%) were receiving antidepressant medications. Demographic and clinical characteristics of study patients were similar to those of all patients receiving care at the clinic during the study period (data not shown).
Clinical and demographic characteristics of HIV-infected study patients by HCV status (N=764)
HCV-infected patients were more likely to have lower nadir CD4+ cell counts (382 vs. 433 cells/mm3, p = 0.01), to have been injection drug users (p<0.001), and to report current illicit drug use within the past 3 months (p<0.001). HCV-infected patients were more likely to report ever use and current use of cocaine, amphetamines, or opiates compared with those without HCV (p values all <0.001). HCV-infected patients were also more often prescribed antidepressant medication (p=0.03). There were no significant differences between those with HCV infection and those without in regards to sex, age, race/ethnicity, at-risk alcohol use, BMI, current CD4+ count, and peak HIV viral load ().
We found a high overall symptom burden, with patients reporting an average of 4.1 symptoms (SD 4.2). Fatigue (43%) and sleep disturbance (34%) were the most common symptoms endorsed (). HCV-infected patients had a higher symptom burden on average than those without HCV, with a symptom score of 4.8 vs. 3.9 (p=0.02).
Prevalence of moderate or severe symptoms among a population of HIV-infected patients (N = 764)
The curvilinear relationship between IRT depression severity scores and standard scores is shown in the scatterplot (). Two hundred and ninety patients (38%) had no depression, 208 (27%) had mild, 126 (17%) had moderate, 82 (11%) had moderately-severe, and 58 (8%) had severe depression defined by standard scores(Kroenke, et al., 2001
). Among HCV-infected patients, 73 (46%) were at least moderately depressed, compared to 193 (32%) of those without HCV (p
= 0.001) () and mean depression severity scores were higher in HCV-infected patients (102 vs. 98, p
Figure 2 Scatter plot and lowess curve of IRT depression scores with standard PHQ-9 scores*
Multivariate linear regression analyses suggested that HCV infection was associated with higher depression severity scores when controlling for differences in age, sex, race, CD4+
count nadir, current CD4+
count, ART status, current illicit drug use, at-risk alcohol use, and BMI. Mean depression severity scores for HCV-infected patients were 3.4 points higher than for patients without HCV in adjusted analyses (). In addition, higher BMI, current illicit drug use, and at-risk alcohol use were associated with higher depression severity scores. The association between HCV and greater depression severity remained significant in models that also adjusted for antidepressant medication use (+2.9, p
=0.02), and in models that also adjusted for any rather than current illicit drug use (+3.4, p
=0.01), or both any and current illicit drug use (+2.9, p
=0.03). Findings were similar in sensitivity analyses using standard PHQ-9 scores and in sensitivity analyses using IRT scores that accounted for DIF rather than naÔve IRT scores (data not shown). HCV infection was associated with more severe depression severity category in sensitivity analyses using ordinal logistic regression with standard PHQ-9 score-based depression symptom severity categories(Kroenke, et al., 2001
)(). HCV infection remained associated with more severe depression in multivariate analyses using reduced depression severity scores constructed from the 6 non-somatic PHQ-9 items (+3.1, p
Change in depression severity scores among HIV-infected patients in routine clinical care using multivariate linear regression (N=764)
Adjusted odds ratios for more severe depression categories using multivariate ordinal logistic regression among HIV-infected patients in routine clinical care (N=764)
To examine whether somatic symptoms including symptoms not typically considered part of the depression construct could potentially be mediating the association between HCV and depression severity scores using a classic approach ()(Baron & Kenny, 1986
), we first demonstrated that HCV was associated with overall symptom burden scores (p
=0.04) in adjusted analyses. Furthermore, HCV was also associated with a number of individual symptoms particularly memory problems, poor appetite, and nausea (p
values 0.006–0.03). We then demonstrated in adjusted models without HCV, that higher overall symptom burden was associated with more severe depression severity scores (p
<0.001). In models with individual symptoms rather than overall symptom burden, memory problems, poor appetite, fatigue, fevers, anxiety, sleep disturbance, sexual dysfunction, and weight loss were all associated with more severe depression symptom severity (p
values<0.001–0.007). Finally, we examined the association between HCV and depression severity scores in adjusted models that included individual somatic symptoms or overall symptom burden scores. When somatic symptoms were included as individual covariates or as overall symptom burden, HCV infection was no longer significantly associated with higher depression severity scores (p
values 0.09–0.1). Fatigue, subjective fevers, memory problems, anxiety, decreased appetite, sleep disturbance, sexual dysfunction, and weight loss were significantly associated with depression severity scores in adjusted models that included all symptoms. Depression severity scores constructed from the 6 non-somatic PHQ-9 items were associated with the same symptoms. Nausea, dizziness, and musculoskeletal pains were not associated with depression severity and were dropped from subsequent analyses.
Mediating role of symptoms in the association between HCV infection and depression symptoms severity
The mean EuroQOL score for the entire study cohort was 0.80 (SD 0.19). HCV-infected patients had worse HRQL, with mean EuroQOL score of 0.76 in HCV-infected patients vs. 0.81 in patients without HCV infection (p=0.01). After accounting for clinical and demographic characteristics (age, race, sex, recent illicit drug use, nadir and recent CD4+ counts and ART status), the association between HCV infection and HRQL was no longer significant (p=0.07).