Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals.

BACKGROUND: Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC). OBJECTIVE: To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years. METHODS: Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups. RESULTS: Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment. CONCLUSIONS: The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.

Teleconsultation for the Pharmaceutical Care of HIV Outpatients in Receipt of Home Antiretrovirals Delivery: Clinical, Economic, and Patient-Perceived Quality Analysis.

Background/Introduction:Pharmacist teleconsultations, combined with home drug delivery or mail-order pharmacy (MOP), can help hospital outpatients with difficulties accessing treatment. The objectives of this study are to describe a teleconsultation protocol and to evaluate clinical, economic, and patient-perceived quality results.Materials and Methods:A cohort observational study was carried out for 3 years on HIV outpatients. Clinical variables were adherence, plasma HIV-RNA, and CD4+ levels. A pharmacoeconomic analysis was carried out through a cost-minimization study. Patient-perceived quality was assessed through a satisfaction survey. Simple random sampling was performed for 95% safety, accuracy ±1%, and losses ±20%.Results:The 38 participants (sample size) consisted of 82% male patients, aged 44.7 ± 8.4 years. There were 854 teleconsultations and 100% treatment adherence. All HIV outpatients kept virally suppressed (p = 1.00) and maintained a controlled immunological level (p = 0.87). The economic evaluation revealed 137 ± 23 € patient/year costs-saved and 18.5 ± 7.2 h/patient/year working time gained. Patient-perceived quality average score was >9.4 out of 10 in all items; the most valued factors were the saving of direct costs and reconciliation with work commitments (45%) and the least valued attributes were making the payment for the shipment and having to adjust to a telephone appointment (41%).Discussion/Conclusions:A teleconsultation protocol associated with home antiretrovirals delivery or MOP obtains a high degree of satisfaction from the HIV hospital outpatients receiving treatment, without repercussions on the therapeutic objectives and with the saving of important direct costs for the patient and indirect costs in relation to labor productivity.

Darunavir/cobicistat maintains the effectiveness of darunavir/ritonavir in HIV-infected patients under mono or dual therapy.

OBJECTIVES: Darunavir/ritonavir (DRV/r) in mono or dual therapy has proven efficacy in selected patients. The aim of this study was to evaluate the efficacy of switching from DRV/r to DRV/cobicistat (DRV/c) in patients under mono or dual therapy. METHODS: This was a prospective multicenter cohort study of patients using DRV/r under mono or dual therapy plus lamivudine who changed to DRV/c maintaining the previous regimen. All patients had a controlled HIV viral load (<50 copies/ml) when switched and were examined every 12 weeks. The primary end-point was the percentage of participants without virological failure (VF) at week 48 in the intent-to-treat analysis. The CD4 cell count and concentrations of cholesterol, triglyceride, and creatinine were measured from baseline to week 48. RESULTS: A total of 162 patients were included: 68.5% were men, and their mean age was 46 ± 12 years. Seventy (43.2%) patients were treated with DRV/r monotherapy, and 92 (56.8%) were treated with DRV/r plus lamivudine. The efficacy at week 48 was 95.1% (95% CI: 90.6%-97.5%) in the intent-to-treat analysis and 98.7% (95.5-99.6%) in the on-treatment analysis. Two VFs were documented but without development of resistance mutations. No significant changes were found in the lipid profile. Creatinine concentration increased significantly by 0.07 mg/dl (0.04-0.10, P < 0.001). CONCLUSIONS: Switching from DRV/r to DRV/c in patients under mono or dual therapy is safe and effective.

Short article: Viral dynamics among hepatitis C virus chronic infected patients during direct-acting antiviral agents therapy: impact for monitoring and optimizing treatment duration.

OBJECTIVES: Direct-acting antiviral agents (DAAs) have provided an ultimate treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being evaluated. Here, the HCV viral dynamics at short times during HCV therapies and its implications for monitoring and optimizing treatment duration have been assessed. PATIENTS AND METHODS: HCV chronic infected patients who began HCV therapy (March 2014 to June 2015) at a reference hospital of the Northwest of Spain were selected. HCV-RNA was quantified at different short time points during HCV therapy using Abbott RealTime HCV assay. Epidemiological, clinical, and virological data were recorded. RESULTS: Eleven HCV-infected patients were included; 90.9% had cirrhosis (>12.5 kPa) and 72.7% were treatment-experienced. HCV genotype 1b was the most prevalent (72.7%). All of the combinations were pegylated interferon-free and all included ribavirin. The median HCV-RNA (log IU/ml) at baseline was 5.8 (5.4-6.1); the decline between baseline and day 3, weeks 4, 8, and 12 was 3.2, 4.8, 5.1, and 5.6, respectively. Fewer than 50% of patients achieved undetectable viral load at weeks 4 and 8; however, all patients achieved a sustained virologic response at 12 weeks. CONCLUSION: Rapid and high HCV-RNA decline was observed among HCV-infected patients under DAA-based regimens, especially for those without cirrhosis. Despite low rates of patients with undetectable HCV-RNA at weeks 4 and 8, all achieved a sustained virologic response at 12 weeks. These findings suggest that the time points to monitor HCV-RNA during DAA therapies and the treatment duration need to be optimized.

Increased incidence of cancer observed in HIV/hepatitis C virus-coinfected patients versus HIV-monoinfected.

BACKGROUND: Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. METHODS: A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups: AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC). Cancer incidence rates were calculated and compared with that observed in the Spanish general population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIRs). A competing risk approach was used to estimate the probability of cancer after HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected patients was also compared using multivariable analysis. RESULTS: A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26 580 patient-years cohort, with an incidence rate of 696 cancers per 100 000 person-years, higher than in the general population (SIR = 3.8). The incidence rate of NADC in HIV/HCV-coinfected patients was 415.0 (SIR = 3.4), significantly higher than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected patients had a higher cumulative incidence of NADC than HIV-monoinfected (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas (adjusted hazard ratio = 1.26). CONCLUSION: PLWH have a higher incidence of NADC than the general population and HCV-coinfection is associated with a higher incidence of NADC. These data justify the need for prevention strategies in these two populations and the importance of eradicating HCV.

Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients.

BACKGROUND: New direct-acting antivirals agents (DAAs) are very safe and well tolerated. OBJECTIVES: The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications. STUDY DESIGN: All HCV-infected patients over 65 years old in clinical follow-up at two Hospitals in Spain who initiated anti-HCV therapy were included (August 2012-October 2015). RESULTS: A total of 120 HCV mono-infected patients were recorded. Mean age of patients was 72.6±7.4years. There were 53.3% women and GT1b was the most frequent (83.3%); 64.2% had cirrhosis and 42.5% were treatment experienced. Ombitasvir+Paritaprevir/r±Dasabuvir±Ribavirin (RBV) and sofosbuvir/ledipasvir±RBV were the most frequently used regimens. Weight-adjusted dosing of RBV was included in 61.7% and 43.6% of them required a dose reduction. Most of the patients (86.7%) had concomitant chronic medication and in 35.8% adjustment was necessary. Adverse events (AE) were seen in 65% of the patients; more frequent when a protease inhibitor (PI) was being used. The sustained virological response (SVR12) per ITT was 88.3%. Only 3 patients discontinued treatment and 2 patients died. CONCLUSIONS: High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The presence of AE was frequent (65%). The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. These findings highlight the high rates of response to DAAs in the elderly HCV-population. However, special caution must be taken when using RBV and a PI.

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection.

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.

Brief Report: European Mitochondrial Haplogroups Impact on Liver Fibrosis Progression Among HCV and HIV/HCV-Coinfected Patients From Northwest Spain.

The impact of mitochondrial DNA haplogroups on the outcome of liver fibrosis was evaluated in 362 hepatitis C virus infection (HCV)-monoinfected and HIV/HCV-coinfected patients (147 and 215, respectively) in clinical follow-up at 2 reference hospitals in the Northwest of Spain. The mitochondrial DNA haplogroup H was the most prevalent (50.3%) in this population. The cluster Others and V were recognized as risk factors for the development of liver fibrosis while haplogroup H and HCV genotype 4 confer a lower risk. This information might be useful for prioritization of HCV treatment, especially for F0-F1 patients for whom there is no urgency for treatment.

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

OBJECTIVES: The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA <50 copies/mL) on ART. METHODS: Newly diagnosed (2004-13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan-Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. RESULTS: A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524-11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA <20 copies/mL) [HR 3.813 (95% CI 0.675-21.535)]. Moreover, only HIV-infected patients with at least three consecutive detected, but not quantified, HIV-RNA determinations showed a higher probability of virological rebound with >200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728-66.261), P = 0.092]. CONCLUSIONS: Blips are frequent (22.7%) among HIV-infected patients with sustained virological suppression on ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL).

High prevalence of subtype F in newly diagnosed HIV-1 persons in northwest Spain and evidence for impaired treatment response.

HIV-1 non-B subtype variants were found in 37.8% of 296 newly diagnosed persons in northwest Spain over the past 5 years. Subtype F was the most prevalent non-B subtype (29.6%) and displayed preferential transmission among MSM. Virologic response rates to antiretroviral therapy were lower among F subtypes compared to B subtypes at weeks 24 (31% vs. 78.3%), 48 (51.7% vs. 85.2%), and 96 (61.1% vs. 94.3%) of therapy. Subtype F was independently associated with virological response at 24 weeks.