Patients with severe mental illness and hepatitis C virus infection benefit from new pangenotypic direct-acting antivirals: Results of a literature review.

INTRODUCTION: Hepatitis C virus (HCV) infection is a global health problem that can results in cirrhosis, hepatocellular carcinoma and even death. HCV infection is 3-20-fold more prevalent among patients with versus without severe mental illness (SMI), such as major depressive disorder, personality disorder, bipolar disorder and schizophrenia. Treatment options for HCV were formerly based on pegylated interferon alpha, which is associated with neuropsychiatric adverse events, and this contributed to the exclusion of patients with SMI from HCV treatment, elimination programmes, and clinical trials. Moreover, the assumption of poor adherence, scant access to healthcare and the stigma and vulnerability of this population emerged as barriers and contributed to the low rates of treatment and efficacy. METHODS: This paper reviews the literature published between December 2010 and December 2020 exploring the epidemiology of HCV in patients with SMI, and vice versa, the effect of HCV infection, barriers to the management of illness in these patients, and benefits of new therapeutic options with pangenotypic direct antiviral agents (DAAs). RESULTS: The approval of DAAs has changed the paradigm of HCV infection treatment. DAAs have proven to be an equally efficacious and safe option that improves quality of life (QoL) in patients SMI. CONCLUSIONS: Knowledge of the consequences of the HCV infection and the benefits of treatment with new pangenotypic DAAs among psychiatrists can increase screening, referral and treatment of HCV infection in patients with SMI.

Prevalence of NS5A resistance associated substitutions in patients with hepatitis C virus genotypes 1a and 3: Impact on current therapeutic strategies.

The presence of resistance-associated substitutions (RASs) at NS5A region might compromise the efficacy of Direct Acting Antiviral agents (DAAs). HCV resistance at NS5A region is mainly focused on patients with hepatitis C virus (HCV) genotypes 1a (G1a) and 3 (G3) with other factors of poor treatment response (ie cirrhosis, prior treatment-exposure, or HCV-RNA >800 000 IU/mL). Herein, we evaluated in a cohort of HCV G1a and G3 infected patients the prevalence of RASs at domain I NS5A using population-based sequencing and the impact of RASs on the optimization of current therapeutic strategies. The RASs considered as clinically relevant were: M28A/G/T, Q30D/E/H/G/K/L/R, L31M/V/F, H58D, and Y93C/H/N/S for G1a and Y93H for G3. A total of 232 patients naïve to NS5A inhibitors were included (166 G1a, 66 G3). The overall prevalence of NS5A RASs for G1a and G3 patients was low (5.5%) or null, respectively. A high proportion of patients harbored, at least, one factor of poor response (78.9% for G1a, and 75.8% for G3). Overall, the rates of patients harboring NS5A RASs in combination with any of the other factors were low and the vast majority of patients (G1a> 94% and G3 100%) could be treated with standard treatments of 12 weeks without ribavirin. In conclusion, testing NS5A RASs in specific HCV-infected populations (ie G1a & G3, cirrhosis, prior treatment experienced, HCV-RNA >800 000 IU/mL) might be useful to optimize current NS5A-based therapies avoiding ribavirin-related toxicities, and shortening treatment duration in the majority of patients.

Plasma mitochondrial DNA levels are inversely associated with HIV-RNA levels and directly with CD4 counts: potential role as a biomarker of HIV replication.

OBJECTIVES: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. METHODS: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. RESULTS: A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 ±âŸ656 copies/µL for naive (31.9%) and 364 ±âŸ939 copies/µL for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 ±âŸ440 copies/µL for those with low-level viraemia (LLV; HIV-RNA 20-200 copies/mL), 265 ±âŸ723 copies/µL for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 ±âŸ1310 copies/µL for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman's rho -0.191, P = 0.003) and directly associated with CD4+ counts (Spearman's rho 0.131, P = 0.046). CONCLUSIONS: Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.

Characterization of chronic HCV infection in Northwest Spain: Impact of the treatment strategic plan of the Spanish National Health Service on HCV cure.

The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.

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.

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).

Long-term clinical experience with darunavir (2007-2015) in a large cohort of HIV-infected patients in Spain.

The clinical experience with the protease inhibitor darunavir/ritonavir (DRV/r) was retrospectively evaluated in a cohort of 173 HIV+ patients who initiated antiretroviral treatment including DRV/r (period 2007-2015). The 43.2% had a CD4 nadir ≤100 cells/mm3 , 64.1% were treatment-experienced, and 36.5% had failed to >3 lines of antiretroviral therapy. Nonetheless, the rate of virological suppression (HIV-RNA <50 copies/ml) in naïve patients was 63%, 66.7%, and 63.6% at 48, 96, and 144 weeks, respectively. The rate of virological suppression in treatment-experienced patients was 62.7%, 78.7%, and 79.1% at 48, 96, and 144 weeks, respectively. No differences were observed according to the immunovirological status neither dosage of DRV/r. Most of them (82.6%) maintained DRV/r treatment. Causes for DRV/r discontinuation were mainly gastrointestinal and cutaneous adverse events (10.5%), switch to simplification treatment strategies (3.5%) and virological failure (1.7%). These findings demonstrate the prolonged efficacy and tolerability of DRV/r even in multi-treated HIV+ patients with an unfavorable immunovirological status. J. Med. Virol. 88:2125-2131, 2016. © 2016 Wiley Periodicals, Inc.

Factors associated with recurrence and survival in liver transplant patients with HCC--a single center retrospective study.

INTRODUCTION: Hepatocellular carcinoma is the most common primary tumor of the liver and is diagnosed in more than a half million people worldwide each year. This study aims to assess factors associated with the recurrence and survival of patients with hepatocellular carcinoma and liver transplantation in a cohort of patients from Medellín, Colombia. MATERIAL AND METHODS: This was a descriptive retrospective study of a consecutive series of liver transplant patients from the Pablo Tobon Uribe Hospital of Medellín from January 2004 to May 2013. Demographic, clinical, imaging, and pathology variables were analyzed. RESULTS: Three hundred thirty liver transplants were performed during the study period, 54 cases (16.4%) had one or more hepatocellular carcinomas in the explant, and 79.6% of these patients were men. Cirrhotic patients had different etiologies, but most of them were due to alcohol abuse (22.2%), followed by hepatitis B virus infection (20.4 %), and hepatitis C virus infection (18.5%). In the pathology specimen, 51.9% had only one focus of hepatocellular carcinoma, 22.2% had two foci and 12.9% had three tumors. Recurrence of hepatocellular carcinoma occurred in 7.4% patients with an average time of 81 months. During follow-up, 25.9% of the patients died in an average time of 67.9 months (CI95 59.1-80.1 months). CONCLUSION: Recurrence and survival of patients with liver transplantation for hepatocellular carcinoma in this study had a similar behavior as that reported in the world literature. The factors associated with these outcomes were vascular invasion, poor tumor differentiation and satellitosis.

Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers.

BACKGROUND AND AIM: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological, and metabolic factors. METHODS: Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (≥ F2) was defined as stiffness > 7.5 kPa, and probable cirrhosis as > 11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses. RESULTS: Ninety-six CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2 ± 2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, P < 0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8-27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced high-density lipoprotein cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, hepatitis B virus DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis. CONCLUSION: Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population.

[Malignancies in HIV-infected patients: descriptive study of 129 cases between 1993 and 2010]. / Neoplasias en pacientes con infección por VIH: Estudio descriptivo de 129 casos en el período 1993-2010.

INTRODUCTION: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). AIM: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. METHODS: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. RESULTS: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. CONCLUSIONS: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.

Safety and Immunogenicity of SARS-CoV-2 vaccines in people with HIV.

OBJECTIVE: To evaluate the safety and the serological response after two doses of mRNA-based SARS-CoV-2 vaccination in people with HIV (PWH). METHODS: Participants were evaluated 4 weeks after the second dose of mRNA-1273 or BNT162b2 vaccine. Tolerability was evaluated with a specific adverse event questionnaire. Patient's sera were analysed using LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin). RESULTS: One-hundred PWH were included, 75% of them men, with a mean age of 44 ±â€Š11 years old, all receiving antiretroviral treatment and mostly with controlled viral loads (98% with HIV RNA <50 copies/ml) and 96% had >200 CD4+/µl. All patients seroconverted after vaccination (antibody concentration ≥33.8 binding antibody units [BAU]/ml). Only 3% of the patients had a low antibody concentration (<520 BAU/ml), whereas 67% of them had concentrations above the assay's detection range (>2080 BAU/ml). Fifty-six patients had local or systemic symptoms, with mild arthromyalgia being the most common systemic symptom. No severe adverse events were reported. CONCLUSIONS: Vaccination with two doses of mRNA-1273 or BNT162b2 is well tolerated in PWH under effective antiretroviral treatment and it leads to a successful antibody response.

Similar CD4/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV.

Background: The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR. Methods: We emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan-Meier method for survival curves. Results: We included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio >0.5, 15% achieved a ratio >1.0, and 6% achieved a ratio >1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio >0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 >1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 >1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs. Conclusions: In this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.

48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Central nervous system disorders in HIV-infected individuals using distinct antiretroviral drugs.

Neuropsychiatric disorders and central nervous system-related symptoms are very common in people with HIV and can have a very negative impact on their quality of life and worsen the prognosis of the disease. These disorders are multifactorial in origin, but may be triggered or worsened by the use of certain antiretroviral treatments. This paper reviews the epidemiology of neuropsychiatric disorders and symptoms in people with HIV, the recommendations and tools available for their early assessment, as well as the neurotoxicity of the main families of antiretroviral (ARV) drugs. It is important to focus on improvement towards the detection of these disorders during the first evaluation or patient follow-up, aimed at improving quality of life. Because of the central nervous system neurotoxicity profile of different antiretroviral drugs, proactive assessment of neuropsychiatric disorders and symptoms prior to treatment start and during follow-up is necessary.

Recent infections among newly diagnosed cases of HIV infection in Spain, 2015-2016. National estimates using cohort data.

BACKGROUND: To estimate the prevalence of recent infection (RI) among people newly diagnosed with HIV in Spain using a representative sample collected by the AIDS Research Network cohort (CoRIS) during 2015-2016. METHODS: Stratified sampling of CoRIS data was used with proportional allocation by mode of transmission of new HIV diagnoses notified to National Surveillance System. Samples used were from patients in the CoRIS cohort with available stored plasma collected within 6 months after diagnosis. Weighted methods were used to estimate the prevalence of RI and multivariate logistic regression models were used to determine associated factors. RESULTS: Of the 669 individuals included, 55.1% were men who had sex with men (MSM), 24.6% were heterosexual, and 20.3% were non-MSM non-heterosexual. The weighted prevalence of RI was 11.8% (95% Confidence interval [CI] 9.4-14.8%) overall, 15.5% (12.2-19.4%) among MSM, 6.3% (3.9-10.0%) among heterosexual, and 8.6% (3.2-20.9%) in non-MSM non-heterosexual persons. Factors associated with prevalence of RI were: MSM (OR 2.05; 95% CI 1.02-4.14) vs. heterosexual, being Spanish (OR 2.92; 1.36-6.26) or European (OR 3.42; 1.28-9.13) vs. Latin American, having a secondary or higher education level (OR 3.08; 0.95-1.00) vs. primary, and having a CD4 count of 350-499 (OR 3.26; 1.46-7.30) or >500 (OR 6.26; 2.92-13.39) vs. <350 cells/mm3. CONCLUSIONS: In the absence of direct data from surveillance systems, the use of cohort data is a very valuable option for identifying the prevalence of RI at national level. This is the first nationwide study carried out in Spain to determine the prevalence of RI using an avidity assay.

Prediction of liver stiffness by serum indexes in HCV-infected patients with or without HIV coinfection.

ABSTRACT: Identification of advanced fibrosis/cirrhosis in hepatitis C virus (HCV)-infected patients should be a mainstay before starting treatment; however, the limited access of many centres to transient elastography (TE) is often a barrier for early assessments. We aimed to investigate the diagnostic accuracy of serum indexes for predicting liver stiffness.Retrospective analysis of HCV patients (with or without HIV coinfection) routinely assessed in 7 centres in Spain. The diagnostic accuracy of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), and their combinations was evaluated using a recent TE examination as a reference test (liver stiffness ≥ 9.5 kPa and ≥12.5 kPa for advanced fibrosis and cirrhosis, respectively). In addition to area under the receiving operating characteristic curves, sensitivity, specificity, and negative predictive value (NPV) and positive predictive value were estimated.The analysis included 1391 patients: 346 (25%) HIV-positive, 732 (53%) people who inject drugs, and 178 (13%) incarcerated. Advanced fibrosis and cirrhosis were found in 557 (40%) and 351 (25%) patients, respectively. APRI < 0.5 (n = 595; 43%) had an NPV of 95% for excluding cirrhosis. Combined FIB-4 < 1.45 with APRI < 0.5 (n = 467; 34%) had an NPV of 87% for excluding advanced fibrosis. Combined APRI > 2 and FIB-4 > 3.25 (n = 134; 10%) had a positive predictive value of 89% for advanced fibrosis. Globally, this approach would avoid the need for TE in 53% of patients. HIV coinfection did not influence diagnostic accuracy.Inexpensive and simple serum indexes confidently allowed identifying the absence of cirrhosis and the presence of advanced fibrosis in 53% of a heterogeneous series of real-world HCV patients with or without HIV infection.

Reasons for Choice of Antiretroviral Regimens in HIV Patients Presenting Late for Initial Treatment in Europe.

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count <200/µL and/or an AIDS-defining disease (late presenters, LPs), is still a challenge, even for HIV specialists. At present, there is little information on the decision process and selection criteria that physicians must take into account when choosing the presumably optimal initial ART for LPs. This study analyzes reasons for the individual choice of first-line ART in HIV LPs. We conducted a prospective multi-center study to analyze the decision-making process of physicians treating naive HIV patients presenting with a CD4 cell count <200/µL and/or an AIDS-defining condition. Two European HIV treatment centers based in Frankfurt (Germany) and A Coruna (Spain) participated in the study. Physicians documented the reasons that led to their decision for a specific first-line ART regimen. A questionnaire was designed for the study. Decisions of the participating physicians were evaluated. A total of 52 treatment decisions were analyzed. Evaluation of the choice of antiretroviral treatment demonstrated that for the overall group of physicians, simplicity of the regimen was the most important selection criterion in 34.6% of cases. The presence of comorbidities was given as the decisive selection criterion in 26.9%, followed by experience with the chosen drugs in 21.2% of cases. In the group of physicians choosing an integrase strand transfer inhibitor (INSTI)-based regimen for first-line ART, the same selection criteria were identified as in the overall group; 33.3% of clinicians selected an INSTI-based regimen because of its simplicity. The presence of comorbidities was the second most frequent decisive criterion (31.0%), followed by personal experience with the prescribed ART (23.8%). In the protease inhibitor group, simplicity was also the most common selection criterion with 40%. Results of clinical trials were stated as the most important criterion for the selection of ART in 38% of all cases, followed by the expected adherence of the patient (22%). Among the physicians who used a non-nucleoside reverse transcriptase inhibitor-based regimen, patients' desire to have children was the most frequent criterion for selection of ART (60%). An ongoing pregnancy was the second most frequent selection criterion, followed by ART's simplicity (8%). For patients treated with a single-tablet regimen, simplicity of ART was comprehensibly the most important decisive criterion (54.5%). Experience with the chosen drugs was the decisive selection criterion in 24.2%, followed by comorbidities in 18.2% of cases. Physicians' selection of individual ART in patients presenting late for first-line treatment seems to be predominantly dependent on patient-centered factors such as adherence issues as well as the clinical experience of physicians with the prescribed drugs.

Hepatitis C Treatment Outcomes in Persons With HIV and Decompensated Cirrhosis Using a Collaborative Multidisciplinary HIV-Centered Approach.

Fifty-four consecutive persons with HIV co-infected with hepatitis C virus (HCV) and liver decompensation were treated with direct-acting antivirals (DAA). The HCV treatment was delivered using a multidisciplinary HIV-coinfection model of care integrating sub-specialty services in 3 countries. Of those treated, 91% (95% confidence interval, 80.1 to 95.9) achieved sustained viral response, and only one person died during treatment. Our study provides evidence that HIV providers achieve excellent outcomes when treating patients with histories of decompensated liver disease, with characteristics similar to those studied using a multidisciplinary HIV-centered approach.

Hepatic safety profile of raltegravir in HIV-infected patients with chronic hepatitis C.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection experience antiretroviral-associated liver toxicity more frequently than HIV mono-infected persons. Herein, we report the hepatic safety profile of raltegravir in a relatively large group of HIV/HCV co-infected patients, a population that was poorly represented in the registrational studies. METHODS: Prospective, observational study of all antiretroviral-experienced HIV-infected patients who initiated raltegravir from January 2006 to January 2009 at a reference HIV clinic. Clinical data, laboratory parameters and liver stiffness measured at baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined following the AIDS Clinical Trials Group definition for liver enzyme elevations (LEEs). A control group of patients who initiated protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly. RESULTS: Data from 218 HIV-infected patients on raltegravir were analysed, 126 HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co-infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three subjects other reasons than raltegravir exposure most likely explained LEEs. Multivariate analysis revealed HCV co-infection as the only independent variable associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally, the rate of LEEs in patients on raltegravir was lower than in those who were treated with PIs or NNRTIs. CONCLUSIONS: LEEs are less frequent in patients treated with raltegravir than with other antiretroviral drug classes. However, HIV/HCV co-infected patients treated with raltegravir experienced LEEs more frequently than HIV mono-infected persons. In this series, LEEs in patients treated with raltegravir were uniformly mild and no cases of grade 3-4 hepatotoxicity could be directly attributed to the drug. These results reinforce the overall hepatic safety profile of raltegravir.