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Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH., (Copyright: © 2023 Permanyer.)

Introduction: Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise., Areas Covered: Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023., Expert Opinion: The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.

Background: Chronic viral hepatitis B, C, and D are the main causes of decompensated cirrhosis and liver cancer worldwide. Newborn HBV vaccination was implemented more than 2 decades ago in most EU countries. Furthermore, potent oral antivirals have been available to treat HBV for 15 years and to cure HCV since 2014. The real-life clinical benefits of these interventions at country level have not been assessed, especially regarding major hepatic outcomes such as cirrhotic decompensation events and hepatocellular carcinoma (HCC)., Methods: Retrospective study of all hospitalizations in Spain having HBV, HCV, and HDV as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 up to 2017., Results: From a total of 73,939,642 hospital admissions during the study period, a diagnosis of HBV, HCV, and HDV was made in 124,915 (1.7‰), 981,985 (13.3‰), and 4850 (0.07‰) patients, respectively. The median age of patients hospitalized within each group was 53.2, 55.9, and 47.0 years, respectively. Significant increases in mean age at hospitalization occurred in all groups (0.6 years older per calendar year on average). The overall rate of hepatic decompensation events for HBV, HCV, and HDV was 12.1%, 14.1%, and 18.8%, respectively. For HCC hospitalizations, these figures were 6.7%, 8.0%, and 7.8%, respectively. Whereas, the rate of decompensation events declined in recent years for HBV, and more recently for HCV, it continued rising up for HDV. Likewise, liver cancer rates recently plateaued for HBV and HCV, but kept growing for HDV., Conclusion: The rate of hepatic decompensation events and liver cancer has declined and/or plateaued in recent years for patients hospitalized with HBV and HCV infections, following the widespread use of oral antiviral therapies for these viruses. In contrast, the rate of decompensated cirrhotic events and HCC has kept rising up for patients with hepatitis delta, for which effective antiviral treatment does not exist yet., (© 2022. Asian Pacific Association for the Study of the Liver.)

Chronic hepatitis C virus (HCV) infection is major cause of decompensated cirrhosis and liver cancer. The advent of curative new antiviral therapies since year 2015 has dramatically improved the prognosis of HCV patients. The real-life clinical benefits at country level of these therapies have not yet been assessed. This is a retrospective study of all hospitalizations in Spain including HCV as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 to 2019. From 81,482,509 nationwide hospital admissions recorded during the study period, 1,057,582 (1.29%) included HCV as diagnosis. The median age of HCV hospitalized patients was 54 years old. Males accounted for 63.2% of cases. Most HCV admissions recorded chronic hepatitis C whereas acute hepatitis C was reported in less than 3%. In-hospital death occurred in 6.4% of HCV admissions. Coinfection with HIV or hepatitis B virus was seen in 14.8% and 6.4%, respectively. Patients hospitalized with HIV-HCV coinfection represented 14.8% of cases and were on average 17 years younger than HCV-monoinfected individuals. The rate of HCV hospitalizations significantly increased until 2005, and then stabilized for one decade. A significant reduction was noticed since 2015. However, whereas the proportion of HCV-associated hepatic decompensation events declined since then, liver cancer diagnoses increased. In conclusion, hospital admissions of HCV individuals significantly declined in Spain since 2015 following a wide prescription of new oral direct-acting antivirals. This reduction was primarily driven by a fall of hepatic decompensation events whereas HCV-related liver cancer continues rising., (© 2022 John Wiley & Sons Ltd.)

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.

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030., (© 2019 John Wiley & Sons Ltd.)

Introduction: The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated. Finally, antiviral activity, safety and potential for drug interactions in phase II/III clinical trials in distinct patient populations are discussed. Expert opinion: The triple co-formulation of sofosbuvir-velpatasvir-voxilaprevir represents a major step towards HCV eradication. It depicts high efficacy even in patients infected with viruses harboring resistance-associated substitutions (RAS), including those selected after DAA failures. Likewise, very high success rates and good tolerance are seen in special patient populations, including decompensated cirrhotics, HIV coinfection, organ transplantation or renal insufficiency. A pill once daily for 8 weeks gives SVR rates above 95%. In prior DAA failures, extending treatment to 12 weeks maximizes SVR rates.

Introduction: The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc.). Whereas discovery of new DAA with increased antiviral activity across all genotypes and over RAS may enhance efficacy, development of fixed dose combinations (FDC) may be the best way to improve drug adherence in difficult-to-treat HCV populations. Areas covered: Three FDC regimens are in the last steps of clinical development for treating hepatitis C. Two distinct nucleotide analogues that inhibit the HCV polymerase, sofosbuvir and uprifosbuvir, are part of the FDC from Gilead and Merck, respectively. The AbbVie dual FDC does not include a polymerase inhibitor. All three new FDC include second-generation NS3 protease inhibitors and NS5A inhibitors active across all HCV genotypes and over common RAS. Expert opinion: Hepatitis C cure rates over 95% are expected with all three next-coming DAA, even in the most difficult-to-treat and/or cure patient populations. These regimens would be particularly needed for the growing number of prior DAA failures. Co-formulations and 8-week shorter treatment lengths will help to overcome drug adherence challenges in certain populations.

Introduction: In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area., Methods: A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing., Results: The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents., Conclusion: Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Introduction: Chronic hepatitis C virus (HCV) infection has become a curable disease. Sustained virologic response rates above 90% have been achieved with recommended direct-acting antiviral (DAA) combinations in most registration trials. However, outcomes in real-world patients are lower. In patients experiencing DAA failure, resistance-associated variants (RAVs) are almost universally selected. At this time it is unclear when and how to re-treat hepatitis C in patients with prior DAA failure., Areas Covered: The rate of DAA failure and predictors of lack of treatment response using distinct DAA combinations are analyzed. We discuss the management of HCV treatment failure and the impact of RAVs on re-treatment strategies., Expert Opinion: Failure to DAA combinations occurs more often in chronic hepatitis C patients with baseline predictors of poor response, such as those with RAVs, genotypes 3 or 1a, advanced liver cirrhosis, elevated serum HCV-RNA and perhaps HIV coinfection. Impaired antiviral efficacy is more frequent when multiple factors are present. On-treatment predictors of DAA failure are poor drug adherence and development of side effects. Extending the length of therapy, adding ribavirin and/or using DAA from other drug families may allow successful re-treatment of most prior DAA failures.

Approximately one-third of people living with HIV are coinfected with hepatitis C virus (HCV). Coinfected individuals experience more rapid liver disease progression on average, and in the era of interferon-based therapy they do not respond as well to antiviral treatment. However, recent studies have suggested that this disparity in treatment response does not apply to interferon-free direct-acting anti-viral (DAA) regimens.

Liver disease is the major complication of chronic HCV infection. However, extrahepatic complications are common (50-75%), including mixed cryoglobulinaemia and B-cell lymphomas. Given that chronic hepatitis C has become curable using expensive oral direct-acting antivirals (DAAs), it seems worth revisiting the whole spectrum and burden of disease in HCV carriers.Herein, we update the most clinically significant medical complications associated with chronic hepatitis C and the evidence of benefits that would derive from a wide use of curative DAA therapies.Chronic HCV infection is associated with a broad spectrum of clinical conditions, including distinct rheumatic disorders (polyarthritis, sicca syndrome), lymphoproliferative conditions (mixed cryoglobulinaemia, monoclonal gammapathies and B-cell lymphomas) and damage at other organs due to persistent systemic inflammation, leading to renal, bone, neurological and/or cardiovascular disease. Eradication of HCV with DAAs is associated with amelioration and/or resolution of most liver-related and extrahepatic complications. Ultimately, gains in quality of life and survival favour treating everyone with hepatitis C regardless of liver fibrosis stage.

Introduction: Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8-24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging., Areas Covered: We address the treatment of chronic hepatitis C with DAA in major special patient populations, such as HIV-positive persons, transplant recipients, patients with advanced cirrhosis, renal insufficiency, hepatitis B or D coinfection, injection drug users (IDUs) and prior DAA failures., Expert Opinion: Drug interactions between DAA and medications given to persons with HIV infection or transplant recipients can result in treatment failure and adverse events. Severe organ dysfunction as in kidney insufficiency or decompensated cirrhosis may lead to DAA overexposure and toxicities. Dysfunctional social circumstances and behavior are associated to poor drug adherence and increased risk for HCV re-infection in active IDUs. Finally, DAA response might be impaired by viral interference in patients with hepatitis B or D coinfection or drug resistance in HCV either at baseline or after prior DAA failures.

Introduction: Roughly 20% of HIV-positive persons worldwide are coinfected with hepatitis C virus (HCV). The recent advent of direct-acting antivirals (DAA) that cure most hepatitis C patients has attracted much attention. Knowledge on drug interactions between DAA and antiretrovirals (ARV) may allow maximizing antiviral efficacy while minimizing drug-related toxicities., Areas Covered: We review the most frequent side effects and clinically significant drug interactions between DAA and ARV. We further discuss how they can be prevented and managed in HIV/HCV-coinfected patients., Expert Opinion: The safety profile of current DAA and the most recently approved ARV is quite favorable. Interactions between DAA and ARV could be frequent in clinical practice. The most common drug interactions affect drug metabolism by inducing or inhibiting the cytochrome P450 system, leading to abnormal drug exposures. Throughout this mechanism HCV and HIV protease inhibitors interact, especially when co-formulated with ritonavir as a pharmacoenhancer, and non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide polymerase inhibitors, and most HCV NS5A inhibitors (i.e., ledipasvir) and HIV integrase inhibitors (i.e., dolutegravir), do not or only marginally affect CYP450, and therefore are free of significant drug interactions. Exposure to HIV and HCV nucleos(t)ide analogues (i.e., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (i.e., P-glycoprotein).

Background: Because of their high cost, the use of direct-acting antivirals (DAAs) is being restricted by many governments to chronic HCV-infected individuals with advanced liver fibrosis. However, response rates are lower and toxicities more frequent in this subset of patients., Methods: All HIV-HCV-coinfected patients followed for at least 3 years at one reference clinic were identified. Liver fibrosis progression (LFP) was defined as a shift from Metavir F0-F2 to F3-F4 estimates (>9.5 KPa) using elastometry., Results: A total of 527 HIV-HCV-coinfected patients were identified, of whom 344 had F0-F2 at baseline. Pegylated interferon/ribavirin therapy was given to 205 patients with null/mild fibrosis, of whom 92 (44.9%) achieved sustained virological response (SVR). After a mean follow-up of 53 months, LFP occurred in 5.4% SVR, 25.7% non-SVR and 18% untreated patients (P=0.005). In multivariate analysis, only achievement of SVR prevented LFP (adjusted hazard ratio 2.1; 95% CI 1.1, 4.1; P=0.01). In 139 untreated patients, only greater baseline elastometry values predicted LFP in multivariate analysis (adjusted hazard ratio 1.84; 95% CI 1.03, 3.3; P=0.03). The area under the receiver operating characteristic (AUROC) curve was 79%. A discriminant threshold of 7.1 kPa gave 68% sensitivity and 82% specificity., Conclusions: In the absence of successful treatment, more than 20% of HIV-HCV-coinfected patients with null/mild liver fibrosis progress to advanced fibrosis within 5 years. Patients with >7.1 kPa (Metavir F2) display the highest risk. Therefore, all coinfected patients with any significant liver fibrosis should be considered as candidates for new DAA-based therapies.

Background: Outbreaks of acute hepatitis C in HIV-positive men who have sex with men (MSM) are being reported in large cities in western countries along with increasing rates of sexually transmitted diseases., Methods: All HIV individuals attended at a large outclinic in Madrid within the last 5 years were examined. Incident syphilis was diagnosed based on rapid plasma reagin (RPR) reactivity, being negative previously or showing >4-fold increase. Acute hepatitis C was diagnosed based on HCV antibody seroconversion and/or positive serum HCV-RNA after being negative within the last year., Results: A total of 859 episodes of syphilis and 19 of acute hepatitis C were diagnosed during the study period. Syphilis was recognized in 65/2,094 (3.1%) individuals attended in 2008 and rose up to 261/2,512 (10.4%) in 2012 (P < 0.001). Acute hepatitis C was diagnosed in only one subject in 2008 but rose up to 7 in 2012 (P = 0.12). All 19 HIV patients with acute hepatitis C were MSM. Syphilis was diagnosed concomitantly in seven. All eight individuals who were treated with peginterferon/ribavirin were cured, whereas only one untreated experienced spontaneous clearance (P = 0.004). Two clusters of infections by HCV genotypes 4 and 1a were identified by phylogenetic analyses., Conclusions: The incidence of acute hepatitis C is low but steadily increasing in HIV-positive MSM in Madrid (<1% yearly), despite the very high rates of syphilis (currently 20% yearly in HIV-positive MSM). Preventive measures for sexually transmitted infections and periodic HCV screening are warranted in this population as treatment of acute hepatitis C is very effective., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Direct acting antivirals (DAA) targeting the HCV serine protease and RNA polymerase have recently entered clinical development. Information about primary resistance to these compounds in HIV-HCV-coinfected patients is scarce., Methods: All individuals newly diagnosed with HIV-1 at several clinics in Madrid between 2000 and 2010 were tested for serum HCV antibody and HCV RNA. The NS3 protease and NS5B polymerase genes were sequenced in all HCV viraemic patients with genotype 1 (G1)., Results: From 1,684 individuals newly diagnosed with HIV-1 during the 10-year study period, 141 (8.4%) were positive for serum HCV RNA. Overall, 58% were infected with G1, being 1a in 64.2% of them. Altogether, 62% of G1a and 30% of G1b harboured HCV drug-resistant changes, with the most common being prQ80K (n=9), prV55A (n=2), polC316Y/N (n=3) and polV499A (n=24). Although no primary resistance mutations were identified for HCV protease inhibitors or nucleoside analogues, mutations C316Y/N and V499A conferring resistance to some non-nucleoside analogues were found in 6% and 51% of G1 patients, respectively., Conclusions: Natural DAA resistance-associated mutations are frequently seen in HIV-HCV-coinfected individuals. Changes polV499A and prQ80K seem to be natural polymorphisms and their effect on treatment outcomes warrants further examination. However, drug resistance testing in HCV drug-naive individuals coinfected with HIV currently does not seem to be warranted before using HCV protease inhibitors and nucleoside analogues. More information is needed for HCV non-nucleoside analogues.

The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country., ((c) 2006 Wiley-Liss, Inc.)

Background: Transfusion-transmitted infections (TTIs) constitute a major health problem worldwide where routine screening of blood or blood products is improperly done, and where non-medical injecting medications and/or drug use are prevalent. Prevalence and risk factors vary by geographic location and by the specific TTI (including HIV-1, HBV, HCV and HTLV-I)., Objective: To determine the prevalence and risk factors associated with TTIs among a sample of multi-transfused adult patients in Peru., Study Design: A cross-sectional multi-center study was conducted across seven major hospitals in Peru from February 2003 to September 2004. Self-reported behavior information (medical procedures, number of sexual partners, and drug use history) was analyzed, along with a review of exposure history from hospital medical records. Prevalences were calculated by TTI for different exposures, along with unadjusted and adjusted odds ratios for infection risk., Results: Overall, 192 (54.7%) of 351 multi-transfused patients were found infected with one or more TTIs. Number of transfusion units, years of transfusion history (6 or more), and number of treatment facilities (2 or more) were associated with HCV infection. Hemodialysis history was a common risk factor associated with HBV, HCV and HTLV-I infection. HIV infection was associated only with total number of transfusion units received., Conclusions: High prevalences of HBV and HCV infection were found among Peruvian multi-transfused patients and were associated with a past history and number of blood transfusions, as well as with past hemodialysis procedures. TTIs continue to represent a significant public health problem in Peru. Continued vigilant attention to blood safety procedures, including universal screening and health care provider education, is recommended.

Oxidative stress accompanying hepatitis C virus (HCV) infection seems to result in mitochondrial (mt) dysfunction. In HIV/HCV-coinfected individuals, HCV-related mt damage could be further enhanced and clinical manifestations of mt damage may appear, particularly following exposure to some antiretroviral drugs. Furthermore, when HCV medications are used together with certain antiretrovirals, the risk of developing mt adverse events may be particularly frequent, such as development of pancreatitis when ribavirin and didanosine are coadministered. The management of HIV/HCV-coinfected individuals needs to consider the high risk of mitochondria-associated toxicities in this population, which may significantly influence treatment decisions and therapeutic modalities.

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus ( HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/ HCV-coinfected patients. A retrospective study was carried out to assess the influence of HCV coinfection on the risk of cardiovascular events in a large cohort of HIV-infected patients recruited since year 2004. A composite event of cardiovascular disease was used as an endpoint, including myocardial infarction, angina pectoris, stroke or death due to any of them. A total of 1136 patients (567 HIV-monoinfected, 70 HCV-monoinfected and 499 HIV/ HCV-coinfected) were analysed. Mean age was 42.7 years, 79% were males, and 46% were former injection drug users. Over a mean follow-up of 79.4 ± 21 months, 3 patients died due to cardiovascular disease, whereas 29 suffered a first episode of coronary ischaemia or stroke. HIV/ HCV-coinfected patients had a greater incidence of cardiovascular disease events and/or death than HIV-monoinfected individuals (4% vs 1.2%, P = 0.004) and HCV-monoinfected persons (4% vs 1.4%, P = 0.5). After adjusting for demographics, virological parameters and classical cardiovascular disease risk factors (smoking, hypertension, diabetes, high LDL cholesterol), both HIV/ HCV coinfection ( HR 2.91; CI 95%: 1.19-7.12; P = 0.02) and hypertension ( HR 3.65; CI 95%: 1.34-9.94; P = 0.01) were independently associated with cardiovascular disease events and/or death in HIV-infected patients. Chronic hepatitis C and hypertension are independently associated with increased cardiovascular disease risk in HIV-infected patients. Therefore, treatment of chronic hepatitis C should be prioritized in HIV/ HCV-coinfected patients regardless of any liver fibrosis staging. [ABSTRACT FROM AUTHOR]

There is scarce information about the impact of antiviral treatment on subsequent progression of liver fibrosis in HIV-infected patients with chronic hepatitis C who experience different outcomes following peginterferon-ribavirin therapy. We conducted a retrospective study of a cohort of HIV/ HCV-coinfected patients with longitudinal assessment of liver fibrosis using elastometry. Patients were split out into four groups according to the prior peginterferon-ribavirin response: sustained virological response ( SVR), relapse (R), partial response ( PR) and null response ( NR). A group of untreated, coinfected patients was taken as control. Significant liver fibrosis progression ( sLFP) was defined as a shift from baseline Metavir estimates ≤F2 to F3-F4, or by >30% increase in liver stiffness in patients with baseline F3-F4. Conversely, significant liver fibrosis regression ( sLFR) was defined as a shift from baseline Metavir estimates F3-F4 to ≤F2, or by >30% reduction in liver stiffness in patients that kept on F3-F4. A total of 498 HIV/HCV-coinfected patients were examined. They were classified as follows: 138 (27.7%) SVR, 40 (8%) R, 61 (12.2%) PR, 71 (14.3%) NR and 188 (37.8%) naive. After a mean follow-up of 53.3 months, sLFP occurred less frequently in patients with SVR (7.2%) compared with R (25%; P = 0.002), PR (23%; P = 0.002), NR (29.6%; P < 0.001) and naïve (19.7%; P = 0.002). Conversely, sLFR was 26.1% in SVR compared with 10% in R ( P = 0.03), 14.8% in PR ( P = 0.06), 16.9% in NR ( P = 0.07) and 10.6% in naïve ( P < 0.001). Sustained clearance of serum HCV- RNA following a course of antiviral treatment is the major determinant of liver fibrosis regression in HIV/ HCV-coinfected patients. [ABSTRACT FROM AUTHOR]