Patient safety culture in South America: a cross-sectional study.

BACKGROUND: Every year, millions of patients suffer injuries or die due to unsafe and poor-quality healthcare. A culture of safety care is crucial to prevent risks, errors and harm that may result from medical assistance. Measurement of patient safety culture (PSC) identifies strengths and weaknesses, serving as a guide to improvement interventions; nevertheless, there is a lack of studies related to PSC in Latin America. AIM: To assess the PSC in South American hospitals. METHODS: A multicentre international cross-sectional study was performed between July and September 2021 by the Latin American Alliance of Health Institutions, composed of four hospitals from Argentina, Brazil, Chile and Colombia. The Hospital Survey on Patient Safety Culture (HSOPSC V.1.0) was used. Participation was voluntary. Subgroup analyses were performed to assess the difference between leadership positions and professional categories. RESULTS: A total of 5695 records were analysed: a 30.1% response rate (range 25%-55%). The highest percentage of positive responses was observed in items related to patient safety as the top priority (89.2%). Contrarily, the lowest percentage was observed in items regarding their mistakes/failures being recorded (23.8%). The strongest dimensions (average score ≥75%) were organisational learning, teamwork within units and management support for patient safety (82%, 79% and 78%, respectively). The dimensions 'requiring improvement' (average score <50%) were staffing and non-punitive responses to error (41% and 37%, respectively). All mean scores were higher in health workers with a leadership position except for the hospital handoff/transitions item. Significant differences were found by professional categories, mainly between physicians, nurses, and other professionals. CONCLUSION: Our findings lead to a better overview of PSC in Latin America, serving as a baseline and benchmarking to facilitate the recognition of weaknesses and to guide quality improvement strategies regionally and globally. Despite South American PSC not being well-exploited, local institutions revealed a strengthened culture of safety care.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on a national project preventing healthcare-associated infections in intensive care units.

Beginning in 2018, a quality improvement collaborative initiative in Brazil successfully reduced the baseline incidence density of healthcare-associated infections in intensive care settings after 2 years. We describe the adaptations of the quality improvement interventions as the COVID-19 pandemic emerged and how the pandemic affected the project outcomes.

A National Implementation Project to Prevent Healthcare-Associated Infections in Intensive Care Units: A Collaborative Initiative Using the Breakthrough Series Model.

Background: Although there are simple and low-cost measures to prevent healthcare-associated infections (HAIs), they remain a major public health problem. Quality issues and a lack of knowledge about HAI control among healthcare professionals may contribute to this scenario. In this study, our aim is to present the implementation of a project to prevent HAIs in intensive care units (ICUs) using the quality improvement (QI) collaborative model Breakthrough Series (BTS). Methods: A QI report was conducted to assess the results of a national project in Brazil between January 2018 and February 2020. A 1-year preintervention analysis was conducted to determine the incidence density baseline of the 3 main HAIs: central line-associated bloodstream infections (CLABSIs), ventilation-associated pneumonia (VAP), and catheter-associated urinary tract infections (CA-UTIs). The BTS methodology was applied during the intervention period to coach and empower healthcare professionals providing evidence-based, structured, systematic, and auditable methodologies and QI tools to improve patients' care outcomes. Results: A total of 116 ICUs were included in this study. The 3 HAIs showed a significant decrease of 43.5%, 52.1%, and 65.8% for CLABSI, VAP, and CA-UTI, respectively. A total of 5140 infections were prevented. Adherence to bundles inversely correlated with the HAI incidence densities: CLABSI insertion and maintenance bundle (R = -0.50, P = .010 and R = -0.85, P < .001, respectively), VAP prevention bundle (R = -0.69, P < .001), and CA-UTI insertion and maintenance bundle (R = -0.82, P < .001 and R = -0.54, P = .004, respectively). Conclusions: Descriptive data from the evaluation of this project show that the BTS methodology is a feasible and promising approach to preventing HAIs in critical care settings.

Prevalence, predictors, and patient-reported outcomes of long COVID in hospitalized and non-hospitalized patients from the city of São Paulo, Brazil.

Background: Robust data comparing long COVID in hospitalized and non-hospitalized patients in middle-income countries are limited. Methods: A retrospective cohort study was conducted in Brazil, including hospitalized and non-hospitalized patients. Long COVID was diagnosed at 90-day follow-up using WHO criteria. Demographic and clinical information, including the depression screening scale (PHQ-2) at day 30, was compared between the groups. If the PHQ-2 score is 3 or greater, major depressive disorder is likely. Logistic regression analysis identified predictors and protective factors for long COVID. Results: A total of 291 hospitalized and 1,118 non-hospitalized patients with COVID-19 were included. The prevalence of long COVID was 47.1% and 49.5%, respectively. Multivariable logistic regression showed female sex (odds ratio [OR] = 4.50, 95% confidence interval (CI) 2.51-8.37), hypertension (OR = 2.90, 95% CI 1.52-5.69), PHQ-2 > 3 (OR = 6.50, 95% CI 1.68-33.4) and corticosteroid use during hospital stay (OR = 2.43, 95% CI 1.20-5.04) as predictors of long COVID in hospitalized patients, while female sex (OR = 2.52, 95% CI 1.95-3.27) and PHQ-2 > 3 (OR = 3.88, 95% CI 2.52-6.16) were predictors in non-hospitalized patients. Conclusion: Long COVID was prevalent in both groups. Positive depression screening at day 30 post-infection can predict long COVID. Early screening of depression helps health staff to identify patients at a higher risk of long COVID, allowing an early diagnosis of the condition.

Implementation of sepsis bundles in public hospitals in Brazil: a prospective study with heterogeneous results.

BACKGROUND: Public hospitals in emerging countries pose a challenge to quality improvement initiatives in sepsis. Our objective was to evaluate the results of a quality improvement initiative in sepsis in a network of public institutions and to assess potential differences between institutions that did or did not achieve a reduction in mortality. METHODS: We conducted a prospective study of patients with sepsis or septic shock. We collected baseline data on compliance with the Surviving Sepsis Campaign 6-h bundles and mortality. Afterward, we initiated a multifaceted quality improvement initiative for patients with sepsis or septic shock in all hospital sectors. The primary outcome was hospital mortality over time. The secondary outcomes were the time to sepsis diagnosis and compliance with the entire 6-h bundles throughout the intervention. We defined successful institutions as those where the mortality rates decreased significantly over time, using a logistic regression model. We analyzed differences over time in the secondary outcomes by comparing the successful institutions with the nonsuccessful ones. We assessed the predictors of in-hospital mortality using logistic regression models. All tests were two-sided, and a p value less than 0.05 indicated statistical significance. RESULTS: We included 3435 patients from the emergency departments (50.7%), wards (34.1%), and intensive care units (15.2%) of 9 institutions. Throughout the intervention, there was an overall reduction in the risk of death, in the proportion of septic shock, and the time to sepsis diagnosis, as well as an improvement in compliance with the 6-h bundle. The time to sepsis diagnosis, but not the compliance with bundles, was associated with a reduction in the risk of death. However, there was a significant reduction in mortality in only two institutions. The reduction in the time to sepsis diagnosis was greater in the successful institutions. By contrast, the nonsuccessful sites had a greater increase in compliance with the 6-h bundle. CONCLUSIONS: Quality improvement initiatives reduced sepsis mortality in public Brazilian institutions, although not in all of them. Early recognition seems to be a more relevant factor than compliance with the 6-h bundle.

HBV primary drug resistance in newly diagnosed HIV-HBV-coinfected individuals in Spain.

BACKGROUND: The wide use of lamivudine (3TC) as oral therapy for chronic HBV infection has favoured the selection and circulation of 3TC-resistant HBV strains worldwide. Although transmission of 3TC-resistant HBV variants has been reported only sporadically, few studies have been conducted in the HIV population where exposure to 3TC has been greater forming part of antiretroviral therapy (ART) regimens. METHODS: All individuals positive for serum hepatitis B surface antigen (HBsAg), newly diagnosed with HIV-1 infection, naive to ART and enrolled in the Spanish HIV cohort (CoRIS) since 2004 were identified. The HBV polymerase gene was sequenced and drug resistance mutations were characterized retrospectively in stored frozen plasma specimens. RESULTS: From 4,419 ART-naive HIV-1-infected individuals, 223 (5.1%) were positive for serum HBsAg. Baseline stored sera were available for 84 patients, of whom 73 could be characterized virologically. This population was mainly represented by men who had sex with men (52.1%), native Spaniards (65.7%) and Latin Americans (16.4%). The mean age was 36 years, mean CD4(+) T-cell count 375 cells/mm(3) and mean plasma HIV RNA 4.5 log(10) copies/ml. The HBV genotype distribution was 64% A, 20% F, 12% D and 4% others. Drug-resistant mutations in the HBV polymerase were found in four (5.5%) patients: two harboured rtL180M, one rtL80V and one rtV173L. CONCLUSIONS: The rate of primary drug resistance in HBV among newly diagnosed HIV-HBV-coinfected patients in Spain is currently low (5.5%) and restricted to 3TC. Thus, HBV drug resistance testing before prescription of oral antiviral therapy is not warranted, although periodic surveillance might be recommended.

Incidence of liver cirrhosis in HIV-infected patients with chronic hepatitis B or C in the era of highly active antiretroviral therapy.

BACKGROUND: Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine the incidence of cirrhosis, using TE assessment, in HIV-infected individuals with chronic hepatitis B or C receiving highly active antiretroviral therapy (HAART). METHODS: A longitudinal study was performed on a cohort of HIV-infected patients with chronic hepatitis B or C who were followed since 2004 at Hospital Carlos III (Madrid, Spain) with periodic TE assessments. The primary outcome was the development of cirrhosis, defined as liver stiffness >12.5 KPa. RESULTS: A total of 508 HIV-infected patients were examined, of whom 54 developed liver cirrhosis during a mean ±(SD) follow-up of 2.6 ±1.0 years (overall incidence was 41.13 cases per 1,000 person-years). The risk of developing cirrhosis was significantly higher in 297 HCV-RNA-positive patients (either untreated or non-responders to hepatitis C therapy) compared with 55 patients who had cleared HCV with therapy (odds ratio 3.73, 95% confidence interval 1.06-13.17; P=0.04). By contrast, the risk of developing cirrhosis was low and similar in 24 HIV-HBV-coinfected patients under long-term suppressive HBV therapy (mainly tenofovir disoproxil fumarate), 132 HIV-infected patients without chronic liver disease and those who had cleared HCV with therapy. CONCLUSIONS: Development of liver cirrhosis in HIV-infected individuals in the HAART era is mainly associated with active HCV coinfection. The risk of developing cirrhosis is negligible in patients who cleared HCV with therapy, as well as in HIV-HBV-coinfected patients on long-term suppressive tenofovir disoproxil fumarate therapy.

Survival of HIV-infected patients with compensated liver cirrhosis.

INTRODUCTION: Since the advent of HAART, liver-related mortality has become the leading cause of non-AIDS deaths in HIV-infected patients in western countries, complications of end-stage liver disease due to chronic hepatitis B, chronic hepatitis C or both being mainly responsible. METHOD: The incidence and predictors of mortality were examined in HIV-infected patients with compensated liver cirrhosis. The accuracy of three different methods (elastometry, Child-Pugh and Model for End-Stage Liver Disease scores) to predict mortality was further examined. Cirrhosis was defined for hepatic elastometry values above 14.5 kPa. RESULTS: A total of 194 (11.4%) out of 1706 HIV-positive individuals were cirrhotic and were prospectively followed since October 2004 until December 2008. Overall, 89% of cirrhotic individuals had chronic hepatitis C, 10.3% chronic hepatitis B, 4.6% hepatitis delta and 4.1% liver disease of other causes or unknown cause. The overall mortality rate was 5.8 deaths per 100 patient-years. Multivariate analyses showed that age of at least 50 years (hazard ratio 4.76, 95% confidence interval 1.66-13.59, P = 0.004), CD4 cell counts below 200 cells/microl (hazard ratio 3.01, 95% confidence interval 1.26-7.23, P = 0.03) and detectable plasma HIV-RNA (hazard ratio 3.97, 95% CI, 1.53-10.27, P = 0.005) were associated with mortality. A baseline Model for End-stage Liver Disease score of at least 11 (P = 0.03) and hepatic elastometry values above 28.75 kPa (P = 0.001) were independent predictors of mortality. CONCLUSION: The death rate in HIV-infected patients with compensated liver cirrhosis in the HAART era is 5.8% yearly, higher than mortality previously reported for either HIV-uninfected individuals with cirrhosis or noncirrhotic HIV-positive patients. Factors associated with mortality were older age, low CD4 cell counts and detectable plasma HIV-RNA. Both Model for End-Stage Liver Disease and especially hepatic elastometry accurately predicted mortality in this population.

Rate and predictors of success in the retreatment of chronic hepatitis C virus in HIV/hepatitis C Virus coinfected patients with prior nonresponse or relapse.

BACKGROUND: In hepatitis C virus (HCV)/HIV-coinfected patients who failed a course of suboptimal hepatitis C therapy, retreatment with adequate doses and duration of pegylated interferon (pegIFN) plus ribavirin (RBV) is advisable in the presence of compensated advanced liver fibrosis. METHODS: The efficacy and safety of pegIFN-alpha2a (180 microg/wk) plus RBV (<75 kg: 1000 mg/d; > or = 75 kg: 1200 mg/d) given for 12 months was prospectively assessed in HIV/HCV patients with nonresponse or relapse to a prior course of suboptimal hepatitis C therapy. The main endpoint was the achievement of sustained virological response (SVR). RESULTS: A total of 52 patients were enrolled in the study (78% HCV genotypes 1 or 4; 56% with advanced liver fibrosis). Prior suboptimal regimens were IFN monotherapy (20%), IFN plus RBV (29%), and pegIFN plus RBV 800 mg/d (51%). Overall, 61% were nonresponders and 39% relapsers. Retreatment provided SVR in 30.8% of patients (19.5% for genotypes 1/4 vs. 72.7% for genotypes 2/3; P = 0.002). In multivariate analysis, HCV genotypes 2/3 [OR 22.2, 95% confidence interval (CI), 2.9-166.7, P = 0.003] and RBV plasma trough concentrations at week 4 [OR 3.9 (95% CI, 1.3-11.8), P = 0.01] were the only independent predictors of SVR. CONCLUSIONS: Retreatment with pegIFN-alpha2a plus weight-based RBV for 12 months permits to achieve HCV clearance in nearly onethird of HIV/HCV-coinfected patients who failed a prior suboptimal course of hepatitis C therapy. Patients with HCV genotypes 2/3 and those with RBV plasma trough levels above 2.07 microg/mL show the highest chances of SVR.

Short communication: transmission of hepatitis B viruses with lamivudine resistance mutations in newly diagnosed HIV individuals.

From 1519 newly diagnosed HIV individuals seen in Madrid between the years 2000 and 2008, 65 (4.3%) were HBsAg(+). Two HIV/HBV-coinfected patients showed the lamivudine resistance mutation M204V in HBV while no drug resistance mutations were recognized in HIV. None of them admitted prior exposure to antiretroviral drugs. Thus, HIV/HBV-coinfected patients might benefit from baseline drug resistance testing for both HIV and HBV to optimize the selection of anti-HBV active antiviral therapy.

Rate and timing of hepatitis C virus relapse after a successful course of pegylated interferon plus ribavirin in HIV-infected and HIV-uninfected patients.

Information on the rate and timing of hepatitis C virus (HCV) relapse after treatment with pegylated interferon plus ribavirin is scarce. Among 604 patients treated for chronic hepatitis C, the 386 who were human immunodeficiency virus (HIV) positive attained an end-of-treatment response less frequently and experienced relapse more often than did the 218 who were HIV negative. However, episodes of HCV relapse occurred before week 12 in most cases, regardless of HIV status.

Hepatitis B in HIV patients: what is the current treatment and what are the challenges?

Chronic hepatitis B affects 5-10% of HIV patients in Western countries. Lamivudine should no longer be used as a single anti-HBV agent in HIV-HBV co-infected patients, given its limited antiviral potency and high risk of selection of resistance, which further results in wide cross-resistance to all other nucleoside analogues. Recent reports of transmission of lamivudine-resistant HBV in HIV patients are of especial concern, and large surveillance studies suggest that it may occur in up to 10% of new HBV infections in Western countries. Another worrisome aspect of the selection of lamivudine-resistant HBV is the potential for selection of vaccine escape mutants. Currently, tenofovir must be viewed as the drug of choice in HIV-HBV co-infected patients in whom antiretroviral therapy is advised. Its co-formulation with emtricitabine (Truvada) is particularly convenient for treating both HIV and HBV in co-infected individuals. While pegIFN-alpha monotherapy for 1 year may be considered for HIV-HBV coinfected individuals with good spontaneous HIV control (elevated CD4 cell count, low plasma HIV-RNA), and certain HBV features (genotype A, HBeAg+, low serum HBV-DNA and elevated ALT), it is clear that very few coinfected patients fulfill these criteria. In HBeAg-negative HIV patients, adefovir may be an option but the relatively low antiviral potency of this drug discourages its wide use. Given its potential anti-HIV activity, both entecavir and telbivudine must only be prescribed with antiretroviral agents. Lack of information about potential pharmacodynamic interactions between entecavir and abacavir (both are guanosine analogues) or between telbivudine and zidovudine or stavudine (all are thymidine analogues) further discourages their concomitant use. At this time, most experts agree that early introduction of anti-HBV active HAART is the best strategy for the treatment of chronic hepatitis B in HIV patients, and Truvada must be part of the triple regimen.

Risk for immune-mediated liver reactions by nevirapine revisited.

Implementation of combination antiretroviral therapies has transformed the prognosis of HIV infection during the past decade. Because of its low-pill burden, convenient administration once or twice daily without food restrictions and, in the case of nevirapine, favorable metabolic profile and proven safety in pregnant women and newborns, nonnucleoside reverse transcriptase inhibitors have been shown to be often superior to protease inhibitors as third agents in combination with a backbone of two nucleoside reverse transcriptase inhibitors. Therefore, two nucleoside reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor are currently the most popular used first-line therapies. Hepatotoxicity during the first weeks of therapy with nevirapine, particularly when initiated in women with CD4 counts > 250 cells/mm3, has prompted changes in guidelines and led to a modification in the product label. Recent data, however, suggest that virologically suppressed patients under any other antiretroviral drug combination may safely switch to nevirapine as a part of a simplification strategy, regardless of their current CD4 count. This subset of patients does not show an increased risk of hepatotoxicity or rash with elevated CD4 counts, as has been reported in drug-naive HIV persons. This information is important and may expand the number of candidates who could benefit from nevirapine use, since a substantial proportion of HIV patients show metabolic abnormalities (dyslipidemia, insulin resistance, liver steatosis) and are at increased cardiovascular risk. Fortunately, many of these conditions may ameliorate or improve using nevirapine.

Papel de tenofovir en la coinfección por el virus de la inmunodeficiencia humana y el virus de la hepatitis C / Role of tenofovir in HIV and hepatitis C virus coinfection

La hepatitis crónica C es frecuente en personas infectadas por el virus de la inmunodeficiencia humana (VIH), particularmente si se han infectado por vía parenteral (p. ej., consumo de drogas intravenosas o transfusión de hemoderivados). Tiene peor pronóstico en el paciente coinfectado por VIH y virus de la hepatitis C (VHC) que en el monoinfectado por VHC, fundamentalmente por la inmunodepresión que provoca el VIH y probablemente por una acción directa del VIH en el hígado. Aunque los antirretrovirales pueden provocar daño hepático, quedan pocas dudas acerca del beneficio neto que se obtiene con la terapia triple en el coinfectado, pues la supresión de la replicación del VIH y la recuperación inmune contribuyen a frenar el daño hepático. Sin embargo, no todos los antirretrovirales son iguales, y en el paciente coinfectado deben priorizarse los fármacos con menor hepatotoxicidad y mejor perfil metabólico, puesto que la esteatosis hepática acelera la progresión de la fibrosis hepática y la resistencia a la insulina dificulta el éxito del tratamiento con interferón y ribavirina. De los análogos de nucleóspidos, el tenofovir es actualmente uno de los más seguros por tener escasa hepatotoxicidad y no interferir negativamente con el tratamiento de la hepatitis C

Chronic hepatitis C virus (HCV) infection is common in HIV-infected individuals, especially if the route of infection is intravenous (e.g. intravenous drug use or blood transfusion). Prognosis is poorer in patients with HCV and HIV coinfection than in those with HCV monoinfection, mainly due to the immunodepression caused by HIV infection and probably also to a direct effect of HIV on the liver. Moreover, although antiretroviral therapy can cause liver damage, there is little doubt about the net benefits obtained with triple therapy in coinfected individuals, since suppression of HIV replication and immune recovery help to halt liver damage. However, not all antiretroviral agents are equal and those with the lowest hepatotoxicity and best metabolic profile should be used in coinfected patients, since hepatic steatosis accelerates progression of hepatic fibrosis and insulin resistance hampers the success of treatment with interferon and ribavirin. Tenofovir is currently one of the safest nucleos(t)ide analogues, due to its low hepatotoxicity and its lack of negative interference on treatment of HCV infection

Papel de tenofovir en la coinfección por el virus de la inmunodeficiencia humana y el virus de la hepatitis C / Role of tenofovir in HIV and hepatitis C virus coinfection

La hepatitis crónica C es frecuente en personas infectadaspor el virus de la inmunodeficiencia humana (VIH),particularmente si se han infectado por vía parenteral (p.ej., consumo de drogas intravenosas o transfusión dehemoderivados). Tiene peor pronóstico en el pacientecoinfectado por VIH y virus de la hepatitis C (VHC) que enel monoinfectado por VHC, fundamentalmente por lainmunodepresión que provoca el VIH y probablementepor una acción directa del VIH en el hígado. Aunque losantirretrovirales pueden provocar daño hepático, quedanpocas dudas acerca del beneficio neto que se obtiene conla terapia triple en el coinfectado, pues la supresión de lareplicación del VIH y la recuperación inmune contribuyena frenar el daño hepático. Sin embargo, no todos losantirretrovirales son iguales, y en el paciente coinfectadodeben priorizarse los fármacos con menorhepatotoxicidad y mejor perfil metabólico, puesto que laesteatosis hepática acelera la progresión de la fibrosishepática y la resistencia a la insulina dificulta el éxito deltratamiento con interferón y ribavirina. De los análogosde nucleóspidos, el tenofovir es actualmente uno de losmás seguros por tener escasa hepatotoxicidad y nointerferir negativamente con el tratamiento de la hepatitis C(AU)

Chronic hepatitis C virus (HCV) infection is common inHIV-infected individuals, especially if the route ofinfection is intravenous (e.g. intravenous drug use orblood transfusion). Prognosis is poorer in patients withHCV and HIV coinfection than in those with HCVmonoinfection, mainly due to the immunodepressioncaused by HIV infection and probably also to a directeffect of HIV on the liver. Moreover, althoughantiretroviral therapy can cause liver damage, there islittle doubt about the net benefits obtained with tripletherapy in coinfected individuals, since suppression of HIV replication and immune recovery help to halt liverdamage. However, not all antiretroviral agents are equaland those with the lowest hepatotoxicity and bestmetabolic profile should be used in coinfected patients,since hepatic steatosis accelerates progression of hepaticfibrosis and insulin resistance hampers the success oftreatment with interferon and ribavirin. Tenofovir iscurrently one of the safest nucleos(t)ide analogues, dueto its low hepatotoxicity and its lack of negativeinterference on treatment of HCV infection(AU)

Management of hepatitis B virus co-infection on and off antiretroviral therapy.

Chronic hepatitis B virus (HBV) infection is recognized in 5% to 10% of persons with HIV. Co-infected individuals show an accelerated course of HBV-associated liver disease with faster progression to cirrhosis. The number of anti-HBV drugs has increased in the past few years, and some agents (eg, lamivudine, emtricitabine, tenofovir) also exert activity against HIV-1. Emergence of drug resistance challenges the long-term benefit of anti-HBV monotherapy. Data derived from studies using new more potent anti-HBV drugs are very promising, and strategies to use these antiretrovirals sequentially or in combination are being developed. Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum HBV-DNA, and drug-resistance testing, along with wise use of antivirals may convert HBV/HIV co-infection in to a manageable disease. Hopefully, this success will translate into a halt of liver-related complications and death in the co-infected population.

Emerging drugs for hepatitis C.

BACKGROUND: Chronic hepatitis C virus (HCV) infection remains a global health threat with approximately 200 million carriers worldwide. Current treatment consists of the use of peginterferon (pegIFN)/ribavirin (RBV) for 24 or 48 weeks depending on HCV genotype. Serious side effects and the fact that less than half of patients infected with HCV genotypes 1 and 4 (which are the most common) accomplish sustained virological response with this medication warrant the need for novel anti-HCV therapies. OBJECTIVE: Description of specifically targeted antiviral therapies for hepatitis C (STAT-C) designed to inhibit the serine protease and the RNA-dependent HCV-RNA polymerase. METHODS: Review of available data reported in peer-reviewed journals and medical conferences. RESULTS/CONCLUSIONS: Early preclinical studies using these compounds produced encouraging results, but the initial enthusiasm has been hampered by toxicity issues and rapid selection of resistance. Therefore, combination therapy with a backbone of pegIFN/RBV, or perhaps in the future using several of these small molecules, preferably having distinct modes of action and resistance profiles, will be required.

[Role of tenofovir in HIV and hepatitis C virus coinfection]. / Papel de tenofovir en la coinfección por el virus de la inmunodeficiencia humana y el virus de la hepatitis C.

Chronic hepatitis C virus (HCV) infection is common in HIV-infected individuals, especially if the route of infection is intravenous (e.g. intravenous drug use or blood transfusion). Prognosis is poorer in patients with HCV and HIV coinfection than in those with HCV monoinfection, mainly due to the immunodepression caused by HIV infection and probably also to a direct effect of HIV on the liver. Moreover, although antiretroviral therapy can cause liver damage, there is little doubt about the net benefits obtained with triple therapy in coinfected individuals, since suppression of HIV replication and immune recovery help to halt liver damage. However, not all antiretroviral agents are equal and those with the lowest hepatotoxicity and best metabolic profile should be used in coinfected patients, since hepatic steatosis accelerates progression of hepatic fibrosis and insulin resistance hampers the success of treatment with interferon and ribavirin. Tenofovir is currently one of the safest nucleos(t)ide analogues, due to its low hepatotoxicity and its lack of negative interference on treatment of HCV infection.