Research Article: Validation of a questionnaire to monitor symptoms in HIV-infected patients during hepatitis C treatment

Date Published: September 20, 2017

Publisher: BioMed Central

Author(s): Edward R. Cachay, Craig Ballard, Bradford Colwell, Francesca Torriani, Charles Hicks, Wm. Christopher Mathews.


Clinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy.

Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV.

The HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC).

From the 103 patients who completed the HCV-SI, 7% were female, 26% non-white, 32% cirrhotics and 91% had undetectable HIV viral loads. Most had genotype 1 (83%) and were HCV treatment-naïve (78%). We treated 19% of patients with pegylated-interferon and ribavirin, 22% with pegylated-interferon, ribavirin, and telaprevir and 59% received interferon-free antivirals. Overall, 77% achieved a sustained virologic response, and 6% discontinued HCV treatment due to side effects. In the treatment discrimination model, compared to the no treatment period, HCV-SI scores were significantly (p < 0.01) lower for interferon-free antivirals and higher for interferon-containing regimens. In the SE-DC model, the total HCV-SI, somatic and neuropsychiatric scores significantly predicted those patients who prematurely discontinued HCV treatment (P < 0.05). The HCV-SI effectively differentiated among treatment regimens known to vary by side effect profiles and between patients with and without treatment discontinuation due to side effects. The HCV-SI may have value as a patient-reported outcome instrument predicting the risk of HCV treatment discontinuation. The online version of this article (doi:10.1186/s12981-017-0182-7) contains supplementary material, which is available to authorized users.

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Direct-acting antivirals (DAA) provide safe and curative treatment for hepatitis C virus (HCV) in patients who start and complete therapy successfully [1].

The Owen Hepatitis Co-Infection Clinic was founded in April 2008 as a multidisciplinary HCV primary care-based program at the University of California San Diego (UCSD) Medical Center. Since its inception, it has used inclusive protocols aimed at increasing HCV treatment uptake among PLWH, including those with ongoing drug use, alcohol consumption, neuropsychiatric disease, and unstable housing while fulfilling our minimum eligibility criteria [9]. In short, the pre-treatment assessment for HCV treatment eligibility among patients with ongoing barriers to care required only: (1) consistent undetectable HIV viral load, (2) stable concurrent medical comorbidities, (3) favorable assessment by the team’s psychiatrist when there is a history of a psychiatric condition that may interfere with treatment, (4) encouraging registration with a needle exchange program for those with ongoing injection drug use, and (5) alcohol sobriety or controlled drinking for at least one month before HCV treatment initiation [9]. To further investigate the psychometric properties of the HCV-SI, we assembled a retrospective longitudinal cohort of adult PLWH treated for HCV between December 2011 and May 2016.

During the study period, we treated 156 PLWH for HCV. Two patients (1.3%) were not eligible to complete the HCV-SI due language barriers. Of the remaining 154, 51 were excluded [five (3.2%) declined to participate, and 46 (29.5%) had fewer than two-time phases completed HCV-SI)] leaving 103 to comprise the study population. There were no differences in demographic characteristics or prevalence of barriers to care (drug or alcohol use, active psychiatric disease or unstable housing), HIV risk factors, CD4 cell count, HIV viral suppression, HCV genotype distribution, cirrhosis diagnosis, prior liver decompensation or prior HCV treatment history outcomes between those patients included versus those excluded from the study (Additional file 2: Table S2). Among the 46 patients who completed the HCV-SI in only one-time phase and were excluded from the main analysis, 25 had documented reasons for lack of completion such as a new competing medical priority (12), failure to return for follow-up and required outreach efforts to ascertain their HCV treatment outcome (5), relocated soon after starting HCV therapy (4), and incarceration (4). Likely patient fatigue was the main reason in 45.6% of patients who completed only one time-phase the HCV-SI (21 of 46). Table 1 shows the demographic, clinical, and HIV characteristics of the study population which were mostly male (93%), white (74%), and had a history of intravenous drug use (IDU—70%). Most patients had HCV genotype 1 infections and were naïve to HCV treatment. Overall, 32% of included patients had cirrhosis. Intolerance to previous HCV treatment was rare (6%). At the time of first HCV-SI measurement, 91% of patients had a suppressed HIV viral load.Table 1Demographic, HCV and HUV related characteristics of study patientsFactorTotal cohort (n = 103)Peg-IFN + RBV(n = 19)Peg-IFN + RBV + TPV (n = 23)IFN-free DAA (n = 61)P value*Age in years, mean (SD)49.7 (9.3)43.6 (12.1)45.3 (7.8)53.2 (7.0)< 0.001 Sex  Female7 (6.8%)2 (11%)3 (13%)2 (3%)0.17  Male96 (93.2%)17 (89%)20 (87%)59 (97%)Race Non-white27 (26.2%)5 (26%)6 (26%)16 (26%)1.00 White76 (73.8%)14 (74%)17 (74%)45 (74%)Ethnicity Not hispanic85 (82.5%)14 (74%)17 (74%)54 (89%)0.14 Hispanic18 (17.5%)5 (26%)6 (26%)7 (11%)HIV risk factor MSM24 (23.3%)4 (21%)3 (13%)17 (28%)0.55 Heterosexual1 (1.0%)0 (0%)0 (0%)1 (2%) Hemophilia6 (5.8%)0 (0%)3 (13%)3 (5%) MSM + IDU45 (43.7%)11 (58%)11 (48%)23 (38%) Heterosexual IDU27 (26.2%)4 (21%)6 (26%)17 (28%)CD4 + in cells/mm3, median (IQR)476.0 (341, 693)607.0 (419, 719)584.0 (426, 772)417 (306, 598)0.045HIV viral load in copies/mL ≤ 5094 (91.3%)17 (89%)20 (87%)59 (97%)1.00 > 509 (8.7%)5 (26%)6 (26%)16 (26%)HCV viral load in millions IU/L, median (IQR)2.0 (0.4, 5.8)3.8 (0.3, 9.7)3.6 (1.2, 17)1.3 (0.4, 3.5)0.017HCV genotype 1/1A/1B86 (83.5%)13 (68%)23 (100%)50 (83%)0.014 24 (3.8%)1 (5%)0 (0%)3 (5%) 311 (10.7%)5 (26%)0 (0%)6 (10%) 42 (1.9%)0 (0%)0 (0%)2 (3%)HCV treatment history Naïve80 (77.7%)19 (100%)16 (70%)45 (74%)0.19 IFN-intolerant6 (5.8%)0 (0%)1 (4%)5 (8%) Relapser10 (9.7%)0 (0%)5 (22%)5 (8%) Null responder6 (5.8%)0 (0%)1 (4%)5 (8%) Cure but reinfected1 (1.0%)0 (0%)0 (0%)1 (2%)Cirrhosis status Non-cirrhotic70 (68.0%)17 (89%)17 (74%)36 (59%)0.032 Cirrhotic33 (32.0%)2 (11%)6 (26%)25 (41%)Prior decompensation or CPS > B Compensated cirrhosis20 (19.4%)2 (11%)4 (17%)14 (23%)0.13 Prior decompensated cirrhosis13 (12.6%)0 (0%)2 (9%)11 (18%) Non-cirrhotic70 (68.0%)17 (89%)17 (74%)36 (59%)SVR on treatment 1 Yes78 (76.5%)12 (63%)13 (57%)53 (88%)1.00 No, null response7 (6.9%)2 (11%)5 (22%)0 (0%) No, relapse4 (3.9%)3 (16%)0 (0%)1 (2%) No, sides effects/adverse events9 (8.8%)2 (11%)5 (22%)2 (3%) No, died during treatment4 (3.9%)0 (0%)0 (0%)4 (7%)Discontinuation due to severe adverse events (1st regimen) No93 (91.2%)17 (89%)18 (78%)58 (97%)0.021 Yes9 (8.8%)2 (11%)5 (22%)2 (3%) No. HCV-SI observations, median (IQR)7.0 (4.0, 12.0)8.0 (6.0, 15.0)15.0 (11.0, 20.05.0 (4.0, 7.0)< 0.001Barriers to care Ongoing drugs/alcohol use30 (29%)8 (42%)7 (30%)15 (25%)0.34 Active psychiatric disease28 (27%)8 (42%)6 (26%)14 (23%)0.26 Unstable housing5 (5%)1 (5%)3 (13%)1 (2%)0.10Peg-IFN Pegylated interferon, IFN Interferon, RBV Ribavirin, DAA Direct acting antiviral, MSM Men who have sex with men, IDU Intravenous drug use, HCV Hepatitis C virus, SVR Sustained viral response, CPS Child–Pugh score, SD Standard deviation, IQR Interquartile range, HCV-SI Hepatitis C symptom inventory* P value for comparison of the 3 groups: Peg-IFN + RBV vs. Peg-IFN + RBV + TPV vs. IFN-Free DAA This study used the HCV-SI to evaluate the evolution of symptoms of PLWH before, during and after HCV treatment, and across three different HCV treatment eras. The HCV-SI discriminated among treatment regimens known to vary by their side effect profiles, and between those patients with and without premature HCV treatment discontinuation due to treatment-related side effects or loss to follow-up. These findings suggest that the HCV-SI can be used to monitor PLWH symptoms while undergoing HCV therapy. The HCV-SI showed discriminant validity across different HCV regimen compositions and identified patients at risk of HCV treatment discontinuation due to adverse events. Medical providers treating HCV among PLWH could consider the HCV-SI as a patient-reported outcome.   Source:


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