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

BACKGROUND: 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. DESIGN: Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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 Impact of Direct-Acting Antivirals in the Hepatitis C-Sustained Viral Response in Human Immunodeficiency Virus-Infected Patients With Ongoing Barriers to Care.

Background. Access to hepatitis C virus (HCV) medications for human immunodeficiency virus (HIV)-infected patients with ongoing barriers to care is restricted by healthcare payers in the absence of HCV treatment outcomes data in the era of direct-acting antivirals (DAA). Methods. Retrospective analysis of HCV treatment outcomes using interferon (IFN)-free DAA regimens and an inclusive treatment protocol in an urban HIV clinic where ongoing barriers to care (drug or alcohol use, psychiatric disease, and/or unstable housing) are common. Then, using logistic regression analysis, we compared the proportion of HIV-infected patients who achieved HCV sustained viral response (SVR) in the pegylated-IFN plus ribavirin (PEG-IFN/RBV, 2008-2011), pegylated-IFN plus ribavirin and telaprevir (PEG-IFN/RBV/PI, 2011-2013), and IFN-free DAA therapy eras (2014). Results are displayed using forest plots. Results. The proportion of patients who achieved HCV SVR in the PEG-IFN/RBV, PEG-IFN/RBV/PI, and IFN-free DAA therapy eras increased from 38.4% (95% confidence interval [CI], 23.2-53.7) and 48% (95% CI, 28.4-67.6) to 83.3% (95% CI, 70.0-96.7), respectively. Similar proportions of patients with ongoing barriers to care were treated during the PEG-IFN/RBV (25 of 39 [64%]), PEG-IFN/RBV/PI (14 of 25 [56%]), and IFN-free DAA (16 of 30 [53%]) eras. Hepatitis C virus SVR among patients with ongoing barriers to care improved from 40% (95% CI, 21-59) to 76.5% (95% CI, 56-97) in the PEG-IFN/RBV and IFN-free DAA eras, respectively. After stratification for factors associated with HCV SVR such as HCV genotype and cirrhosis, HCV SVR were similar in patients regardless of the presence of ongoing barriers to care. Conclusions. Using IFN-free DAA and an inclusive HCV treatment protocol, 76.5% of HIV/HCV-treated patients with ongoing barriers to care achieved HCV SVR.

Outcomes of pharmacist-assisted management of antiretroviral therapy in patients with HIV infection: A risk-adjusted analysis.

PURPOSE: The impact of pharmacist-assisted management (PAM) of pharmacotherapy for patients with human immunodeficiency virus (HIV) infection was investigated. METHODS: A retrospective cohort analysis was conducted to evaluate antiretroviral therapy (ART) outcomes in treatment-naive patients initiated on ART at an HIV clinic. Eligible patients enrolled in the clinic during the period 1999-2013 were classified into two groups: those referred to a clinic-based HIV pharmacist for initiation of ART (the PAM group) and those managed by a primary care provider (the control group). The primary study objective was the median time to viral suppression; secondary objectives included the durability of response to the first ART regimen. Relative hazards for the events of interest were estimated using a marginal structural Cox proportional hazards model and Kaplan-Meier curves, with inverse probability weights used to control for selection and confounding bias. RESULTS: Patients referred for PAM services (n = 819) typically had higher baseline viral loads and lower CD4+ cell counts than those in the control group (n = 436). The likelihood of viral suppression during the first two years after ART initiation was significantly higher in the PAM group versus the control group (hazard ratio, 1.37; 95% confidence interval, 1.18-1.59; p < 0.0001). The median durability of the first ART regimen was 100 months in the PAM group versus 44 months in the control group (p > 0.05). CONCLUSION: In treatment-naive patients, suppression of HIV viral load occurred earlier when pharmacists assisted with initiating ART than when ART was initiated without that assistance.

The hepatitis C cascade of care among HIV infected patients: a call to address ongoing barriers to care.

BACKGROUND: The aims were to investigate the hepatitis C (HCV) cascade of care among HIV-infected patients and to identify reasons for not referring for and not initiating HCV therapy after completion of HCV treatment staging. DESIGN AND METHODS: Retrospective cohort analysis of HIV-infected patients under care at the University of California, San Diego (UCSD). We identified patients screened for and diagnosed with active HCV infection. Logistic regression analyses were used to identify factors associated with lack of referral for HCV therapy. Electronic medical records were reviewed to ascertain reasons for not initiating HCV therapy. RESULTS: Between 2008 and 2012, 4725 HIV-infected patients received care at the UCSD Owen clinic. Most patients [4534 (96%)] were screened for HCV, 748 (16%) patients had reactive serum HCV antibodies but only 542 patients had active HCV infection. Lack of engagement in care was the most important predictor of non-referral for HCV therapy [odds ratio (OR): 5.08, 95% confidence interval 3.24-6.97, p<0.00001]. Other significant predictors included unstable housing (OR: 2.26), AIDS (OR: 1.83), having a detectable HIV viral load (OR: 1.98) and being non-white (OR: 1.67). The most common reason (40%) for not initiating or deferring HCV therapy was the presence of ongoing barriers to care. CONCLUSIONS: Screening for HCV in HIV-infected patients linked to care is high but almost half of patients diagnosed with HCV are not referred for HCV therapy. Despite improvements in HCV therapy the benefits will not be realized unless effective measures for dealing with barriers to care are implemented.

High incidence of serious adverse events in HIV-infected patients treated with a telaprevir-based hepatitis C virus treatment regimen.

OBJECTIVES: To report the rates of grade IV adverse events and hepatitis C virus (HCV) treatment discontinuation associated with the use of telaprevir, pegylated interferon, and ribavirin. DESIGN: Retrospective cohort analysis. METHODS: The study included patients coinfected with HIV and HCV who underwent HCV treatment in a clinic-based setting with telaprevir, pegylated interferon, and ribavirin. The United States of America National Institutes of Health Division of AIDS grading system was used to rate severity of adverse events. RESULTS: Of the 24 consecutive patients treated for HCV using telaprevir/pegylated interferon/ribavirin, 50% (12/24) developed serious adverse events and 29% (7/24) discontinued HCV treatment due to adverse events, despite an intensive multidisciplinary monitoring approach. CONCLUSION: In this HIV clinic-based experience, a high rate of grade IV adverse events and treatment discontinuations were observed associated with HCV telaprevir-based treatment. Careful consideration of the risks and benefits of telaprevir-based therapy should be undertaken, given prospects for interferon-sparing therapy in the near future.

Increasing Hepatitis C treatment uptake among HIV-infected patients using an HIV primary care model.

BACKGROUND: Access to Hepatitis C (HCV) care is low among HIV-infected individuals, highlighting the need for new models to deliver care for this population. METHODS: Retrospective cohort analysis that compared the number of HIV patients who initiated HCV therapy: hepatology (2005-2008) vs. HIV primary care model (2008-2011). Logistic-regression modeling was used to ascertain factors associated with HCV therapy initiation and achievement of sustained viral response (SVR). RESULTS: Of 196 and 163 patients that were enrolled in the HIV primary care and hepatology models, 48 and 26 were treated for HCV, respectively (p = 0.043). The HIV/HCV-patient referral rate did not differ during the two study periods (0.10 vs. 0.12/patient-yr, p = 0.18). In unadjusted analysis, predictors (p < 0.05) of HCV treatment initiation included referral to the HIV primary care model (OR: 1.7), a CD4+ count ≥400/mm3 (OR: 1.8) and alanine aminotranferase level ≥63U/L (OR: 1.9). Prior psychiatric medication use correlated negatively with HCV treatment initiation (OR: 0.6, p = 0.045). In adjusted analysis the strongest predictor of HCV treatment initiation was CD4+ count (≥400/mm3, OR: 2.1, p = 0.01). There was no significant difference in either clinic model (primary care vs. hepatology) in the rates of treatment discontinuation due to adverse events (29% vs. 16%), loss to follow-up (8 vs. 8%), or HCV SVR (44 vs. 35%). CONCLUSIONS: Using a HIV primary care model increased the number of HIV patients who initiate HCV therapy with comparable outcomes to a hepatology model.

Reliability and predictive validity of a hepatitis-related symptom inventory in HIV-infected individuals referred for Hepatitis C treatment.

BACKGROUND: We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients. METHODS: Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals. The symptom inventory was factor analyzed and subscale reliability estimated with Cronbach's alpha. Predictive validity was evaluated using generalized estimating equations (GEE). Predictors of HCV treatment were identified using logistic regression. RESULTS: Between April 2008 to July 2010, 126 HIV/HCV co-infected patients were enrolled in the study. Factor analysis using data from 126 patients yielded a three-factor structure explaining 60% of the variance for the inventory. Factor 1 (neuropsychiatric symptoms) had 14 items, factor 2 (somatic symptoms) had eleven items, and factor 3 (sleep symptoms) had two items, explaining 28%, 22% and 11% of the variance, respectively. The three factor subscales demonstrated high intrinsic consistency reliability. GEE modeling of the 32 patients who initiated HCV therapy showed that patients developed worsening neuropsychiatric and somatic symptoms following HCV therapy with stable sleep symptoms. Bivariate analyses identified the following as predictors of HCV therapy initiation: lower HIV log10 RNA, lower scores for neuropsychiatric, somatic and sleep symptoms, lower CES-D scores and white ethnicity. In stepwise multiple logistic regression analysis, low neuropsychiatric symptom score was the strongest independent predictor of HCV therapy initiation and HIV log10 RNA was inversely associated with a decision to initiate HCV treatment. CONCLUSIONS: A 41-item hepatitis-related symptom inventory was found to have a clinically meaningful 3-factor structure with excellent internal consistency reliability and predictive validity. In adjusted analysis, low neuropsychiatric symptom scores and controlled HIV infection were independent predictors of HCV treatment initiation. The usefulness of the HCV symptom inventory in monitoring HCV treatment should be evaluated prospectively.

Predictive validity of a brief antiretroviral adherence index: retrospective cohort analysis under conditions of repetitive administration.

BACKGROUND: Newer antiretroviral (ARV) agents have improved pharmacokinetics, potency, and tolerability and have enabled the design of regimens with improved virologic outcomes. Successful antiretroviral therapy is dependent on patient adherence. In previous research, we validated a subset of items from the ACTG adherence battery as prognostic of virologic suppression at 6 months and correlated with adherence estimates from the Medication Event Monitoring System (MEMS). The objective of the current study was to validate the longitudinal use of the Owen Clinic adherence index in analyses of time to initial virologic suppression and maintenance of suppression. RESULTS: 278 patients (naïve n = 168, experienced n = 110) met inclusion criteria. Median [range] time on the first regimen during the study period was 286 (30 - 1221) days. 217 patients (78%) achieved an undetectable plasma viral load (pVL) at median 63 days. 8.3% (18/217) of patients experienced viral rebound (pVL > 400) after initial suppression. Adherence scores varied from 0 - 25 (mean 1.06, median 0). The lowest detectable adherence score cut point using this instrument was >/= 5 for both initial suppression and maintenance of suppression. In the final Cox model of time to first undetectable pVL, controlling for prior treatment experience and baseline viral load, the adjusted hazard ratio for time updated adherence score was 0.36(score >/= 5) (95% CI: 0.19-0.69) [reference: <5]. In the final generalized estimating equations (GEE) logistic regression model the adjusted odds ratio for time-updated adherence score was 0.17(score >/= 5) (0.05-0.66) [reference: <5]. CONCLUSION: A brief, longitudinally administered self report adherence instrument predicted both initial virologic suppression and maintenance of suppression in patients using contemporary ARV regimens. The survey can be used for identification of sub-optimal adherence with subsequent appropriate intervention.