B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin.

Real-world data evaluating the effectiveness of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) treatment have been reported from different regions. Our aim was to evaluate the effectiveness and clinical outcomes of daclatasvir (DCV) and sofosbuvir (SOF) ± ribavirin (RBV) in a prospective multicentre cohort study including patients from Argentina and Brazil who received DCV/SOF ± RBV for 12 or 24 weeks from 2015 to 2018. Multivariable logistic regression models were carried out to identify factors associated with failure to achieve sustained virologic response (SVR) as a primary end point, and to death, decompensation, hepatocellular carcinoma (HCC) or liver transplantation (LT) as a composite secondary end point. From a total of 1517 patients treated with DCV/SOF, 906 completed 12 weeks post-treatment evaluation and were included in the analysis. Overall SVR12 rate was 96.1% (95% CI: 94.6%-97.2%), and 95% (95% CI: 92.8%-96.6%) in patients with cirrhosis. LT recipients and presence of cirrhosis were independently associated with failure to achieve SVR. During post-SVR12 follow-up, cumulative incidence of the secondary end point was 2.4% (95% CI: 1.5%-3.6%); two patients died from nonliver-related causes and two from HCC, five underwent LT, 12 developed HCC and 17 patients developed hepatic decompensation. Independent variables associated with these composite secondary end points were prior to HCV treatment and presence of cirrhosis. In conclusion, although the high pangenotypic effectiveness of DCV/SOF ± RBV was confirmed in our real-life cohort, patients with compensated and decompensated cirrhosis showed higher risk of non-SVR and complication appearance during treatment or after achieving SVR.

Treatment of Chronic HCV Infection with the New Direct Acting Antivirals (DAA): First Report of a Real World Experience in Southern Brazil.

INTRODUCTION AND AIM: There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. MATERIALS AND METHODS: Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis. RESULTS: 219 patients were analyzed. Mean age was 57.4 ± 10.9 years and 142/219 (64.8%) were male. Genotype 1 was present in 166 patients (75.8%; 1a 29.2%, 1b 46.6%); Genotypes 2, 3 and 4 in 8 (3.7%), 43 (19.6%) and 2 (0.9%), respectively. 96 (43.8%) were cirrhotic. 134 (59.5%) were treatment experienced. DAA therapies were: sofosbuvir (SOF) + ribavirin (RBV) in 10 patients; SOF + simeprevir (SMV) ± RBV in 73; SOF + pegylated interferon (PEG-IFN) + RBV in 6; SOF + daclatasvir (DCV) ± RBV in 51, SOF + ledipasvir (LDV) ± RBV in 61, and paritaprevir/ ritonavir + ombitasvir + dasabuvir (PTVr/OBV/DSV) ± RBV in 18 patients. SVR-12 was achieved in 208/219 (95%). Ten patients had virologic failure: 6 cirrhotic, 7 treatment experienced, and 6 either genotype 3 or 1a. No adverse event was attributed to the DAA therapy. CONCLUSIONS: Real world experience with DAA therapy in Southern Brazil showed a high rate of SVR and excellent tolerability. Failure to achieve SVR was mainly observed among patients with at least one negative predictor of response: cirrhosis and/or genotypes 1a or 3.

People living with HIV on ART have accurate perception of lipodystrophy signs: a cross-sectional study.

BACKGROUND: The prevalence of lipodystrophy ranges from 31 to 65%, depending on the criteria adopted for diagnosis. The usual methods applied in the diagnosis vary from self-perception, medical examination, skinfolds measurements, or even imaging assessment for confirmation of fat distribution changes. Although several methods have been developed, there is no gold standard for characterization of LA and LH, or mixed forms. This study aimed to compare self-reported signs of lipodystrophy with objective measures by skinfolds and circumferences, and to evaluate the prevalence of lipoatrophy (LA) and lipohypertrophy (LH) among subjects living with HIV/AIDS on ART. METHODS: A cross-sectional study enrolled participants living with HIV/AIDS receiving ART, aged 18 years or older from an outpatient health care center, in Southern Brazil. Self-reported body fat enlargement in the abdomen, chest or breasts, and dorsocervical fat pad were used to determine LH, while LA was identified by self-reported fat wasting of the face, neck, legs, arms or buttocks. Measurements were obtained with a scientific caliper for infraorbital, buccal, and submandibular skinfolds, and using an inelastic tape to measure circumferences of waist, hip, neck, and arm. LH and LA were established by the presence of at least one self-reported sign. RESULTS: Comparisons of self-reported signs with objective measurements for men and women were carried out in 815 participants on ART, out of 1240 participants with HIV infection. Self-report of decreased facial fat and sunken cheeks was associated with lower infraorbital, buccal, and submandibular skinfolds. Participants who reported buffalo hump had, on average, greater neck circumference, as well as those who have increased waist circumference also reported abdominal enlargement, but no buttock wasting. Men were most commonly affected by lipoatrophy (73 vs. 53%; P < 0.001), and women by lipohypertrophy (79 vs. 56%; P < 0.001). CONCLUSION: In conclusion, self-reported signs of lipodystrophy and lipoatrophy are prevalent, differ by gender, and are associated with objective measurements in people living with HIV/AIDS.

Alcohol Drinking Pattern: A Comparison between HIV-Infected Patients and Individuals from the General Population.

BACKGROUND: Alcohol consumption is highly prevalent in the general population and among HIV-infected population. This study aimed to compare the pattern of alcohol consumption and to describe characteristics associated with heavy alcohol consumption in individuals from the general population with patients infected with HIV. METHODS: Participants for this analysis came from a population-based cross-sectional study and from a consecutive sampling of patients infected with HIV. Participants aged 18 years or older were interviewed using similar questionnaires with questions pertaining to socio-demographic characteristics, alcohol consumption, smoking, physical activity, and HIV-related characteristics, among others. Blood pressure and anthropometric measures were measured using standardized procedures. RESULTS: Weekly alcohol consumption was more prevalent among individuals from the general population than HIV-infected patients: 57.0 vs. 31.1%, P<0.001. The prevalence of heavy episodic drinking was higher in the population sample as well: 46.1 vs. 17.0%, P<0.001. In the general population, heavy alcohol consumption was more prevalent in men. Cigarette smoking was independently associated with heavy alcohol consumption among HIV infected (Prevalence Ratio; PR = 5.9; 95%CI 2.6-13.9; P<0,001) and general population (PR = 2.6; 95%CI 1.9-3.0; P<0.001). Years at school were inversely associated with heavy alcohol consumption among HIV-infected patients and directly associated among participants from the general population, even after controlling for sex, age, skin color, and smoking. CONCLUSIONS: Heavy alcohol consumption is more prevalent in the general population than among HIV-infected patients. Individuals aware about their disease may reduce the amount of alcoholic beverages consumption comparatively to healthy individuals from the general population.

Biochemical non-invasive assessment of liver fibrosis cannot replace biopsy in HIV-HCV coinfected patients.

BACKGROUND AND RATIONALE: The liver biopsy has been considered the gold standard for the diagnosis and quantification of fibrosis. However, this method presents limitations. In addition, the non-invasive evaluation of liver fibrosis is a challenge. The aim of this study was to validate the fibrosis cirrhosis index (FCI) index in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, and compare to AST/ALT ratio (AAR), AST to platelet ratio index (APRI) and FIB-4 scores, as a tool for the assessment of liver fibrosis in coinfected patients. MATERIAL AND METHODS: Retrospective cross sectional study including 92 HIV-HCV coinfected patients evaluated in two reference centers for HIV treatment in the Public Health System in Southern Brazil. Patients who underwent liver biopsy for any indication and had concomitant laboratory data in the 3 months prior to liver biopsy, to allow the calculation of studied noninvasive markers (AAR, APRI, FIB-4 and FCI) were included. RESULTS: APRI < 0.5 presents the higher specificity to detect no or minimal fibrosis, whereas APRI > 1.5 presents the best negative predictive value and FCI > 1.25 the best specificity to detect significant fibrosis. The values of noninvasive markers for each Metavir fibrosis stage showed statistically significant differences only for APRI. In conclusion, until better noninvasive markers for liver fibrosis are developed and validated for HIV-HCV coinfected patients, noninvasive serum markers should be used carefully in this population.

Comparison between potential risk factors for cardiovascular disease in people living with HIV/AIDS in areas of Brazil.

INTRODUCTION: Coronary heart disease and its risk factors depend on genetic characteristics, behaviors, and habits, all of which vary in different regions. The use of antiretroviral therapy (ARV) has increased the survival of people living with HIV/AIDS (PLWHA), who begin to present mortality indicators similar to the general population. This study aimed to compare the prevalence of factors potentially associated with coronary heart disease in three cohorts of PLWHA from three different regions of Brazil. METHODOLOGY: The study population was composed of participants of the cohorts of Pernambuco, Goiás, and Rio Grande do Sul states. In these sites, adult patients attending reference centers for treatment of HIV/AIDS were consecutively enrolled. RESULTS: Pernambuco and Goiás had a higher proportion of males and of individuals with high-risk high-density lipoprotein (HDL). Pernambuco also had a greater proportion of individuals with hypertension, elevated triglycerides, and CD4 counts below 200 cells/mm(3). Lower education was more frequent in Rio Grande do Sul, and the use of cocaine was higher in this state. CONCLUSIONS: The results confirm the importance of risk factors for coronary heart disease in PLHIV and highlight differences in the three cohorts. Specific measures against smoking and sedentary lifestyle, avoidance of advanced stages of immunosuppression, and appropriate treatment of dyslipidemia and dysglicemia are urgently needed to cope with the disease in Brazil.

Risk of coronary heart disease among HIV-infected patients: a multicenter study in Brazil.

Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 ± 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score ≥10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score ≥10 was similar between regions for males, patients aged ≥60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population.

Association of blood pressure and hypertension with alcohol consumption in HIV-infected white and nonwhite patients.

INTRODUCTION: Although alcohol abuse is associated with hypertension in whites and nonwhites, it has been scarcely investigated in HIV-infected patients. OBJECTIVE: To investigate whether the association of alcohol abuse with hypertension is influenced by skin color in HIV-infected individuals. METHODS: Cross-sectional study in HIV-infected individuals aged 18 years or older. Demographic characteristics, lifestyle, and HIV infection were investigated. Alcohol abuse was defined as ≥ 15 (women) and ≥ 30 g/alcohol/day (men), and binge drinking by the intake of ≥ 5 drinks on a single occasion. Hypertension was defined by blood pressure ≥ 140/90 mmHg or use of blood pressure-lowering agents. RESULTS: We studied 1,240 individuals, with 39.1 ± 10 years, 51% males and 57% whites. Age and body mass index were associated with blood pressure, and there was an independent association of alcohol abuse with hypertension in whites (RR = 1.9, 95% CI 1.1-3.3) and nonwhites (RR = 2.4, 95% CI 1.4 to 4.0). Among nonwhite individuals who were alcohol abusers, systolic (9.3 ± 3.2; P = 0.001) and diastolic blood pressures (6.4 ± 2.1; P = 0.008) were higher than in nonabusers. CONCLUSION: Alcohol abuse is a risk factor for hypertension in white and nonwhite HIV-infected individuals. The association of ethanol consumption with blood pressure is not explained by AIDS-related conditions.

Metabolic syndrome and population attributable risk among HIV/AIDS patients: comparison between NCEP-ATPIII, IDF and AHA/NHLBI definitions.

BACKGROUND: Metabolic Syndrome (MetS) is based on the same individual components, but has received several amendments to the original definition. In this study, we verified the prevalence of metabolic syndrome according to different criteria, and the impact of each component on the diagnostic. METHODS: This cross-sectional study enrolled HIV infected patients from a HIV/AIDS reference Center in southern Brazil. Metabolic syndrome was identified according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII), the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) criteria, and using a standardized questionnaire and blood testing. RESULTS: A sample of 1240, out of 1295, HIV-infected patients was enrolled. Males were on average older, more educated, and had shorter time since the HIV diagnosis. The population attributable risk (PAR) for waist circumference explained 80% of the prevalence among men and women (AHA/NHLBI criteria). Triglycerides had the highest impact on prevalence of metabolic syndrome according to all criteria, independently of age, skin color and HAART use, among men. CONCLUSIONS: In this large sample of HIV infected patients, the overall prevalence of metabolic syndrome, under either classification, was noticeable and the AHA/NHLBI definition accounted for the highest prevalence.

Physical activity: do patients infected with HIV practice? How much? A systematic review.

Several studies have suggested that aerobic physical activity is safe and beneficial for HIV-infected adults. However, there is information lacking regarding whether HIV-infected patients practice physical activity and to what extent. Therefore, the aim of this systematic review was to determine the prevalence of physical activity, sedentary lifestyle or lack of physical activity in non-experimental conditions performed by HIV-infected subjects. The electronic search was conducted using Medline and EMBASE bibliographic databases and the platforms of Bireme, Ovid, Science Direct, High Wire and SCIELO from January 1990 to July 2011. Original observational studies were included. Of the 2,838 articles found, 48 met the inclusion criteria. Following data extraction and after reading the manuscripts, 24 were selected for systematic review. Of the 24 studies, most were cross-sectional studies. The average quality score using the modified Newcastle-Ottawa scale was 2.8±1.5. The diversity of methods used to assess physical activity precluded the calculated summary estimate of prevalence. The percentage of sedentary lifestyle was determined in 13 articles which conducted studies on HIV-infected individuals. The percentage of sedentary lifestyle or physical inactivity ranged from 19%to 73%, with the level determined by different methods. In conclusion, there are few well-designed studies with adequate sample size to represent the population of HIV-infected individuals. A pooled estimate could not be calculated due to the differences in physical activity measurements and definitions of physically active and non-active HIV-infected individuals.

Independent predictors of metabolic syndrome in HIV-infected patients.

Metabolic syndrome (MetS) is associated with development of type 2 diabetes mellitus and increased risk for cardiovascular disease. However, a few studies have assessed its prevalence and risk factors among HIV patients from developing countries. The aim of this study was to identify independent risk factors for metabolic syndrome by the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) among HIV-infected men and women. A cross-sectional study enrolled patients, aged 18 years or older, who sought to confirm the diagnosis or sought treatment in the outpatient service of a public health care center in southern Brazil. From June 2006 to December 2008, certified research assistants conducted interviews using standardized questionnaires and anthropometric measurements. Fasting blood sample was collected, use of highly active antiretroviral therapy (HAART) was ascertained, and MetS was characterized by AHA/NHLBI criteria. In the total, 1240 of 1295 HIV-infected patients were included. MetS prevalence was 24.7% and was similar among men and women. Among men, age, education, physical activity, body mass index (BMI), and HAART use were independently associated with MetS, while among women, there were associations with age, BMI, and use of protease inhibitors. In conclusion, high prevalence of MetS was detected in HIV-infected men and women. In both genders, age and BMI were directly and independently associated with MetS. The association between the use of HAART and MetS was confirmed among men but not among women.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55 percent) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3 percent) vs. 8 (17 percent) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Co-infection by hepatitis C virus in HIV-infected patients in southern Brazil: genotype distribution and clinical correlates.

BACKGROUND: Prevalence rates of hepatitis C virus (HCV) co-infection, the distribution of HCV genotypes, and the frequency of spontaneous resolution of hepatitis C in patients infected with the Human Immunodeficiency Virus (HIV) have a worldwide disparity. The purpose of this study is to investigate the prevalence of HCV antibodies (anti-HCV) in patients with HIV, the proportion and correlates of infection by different HCV genotypes, and rates of spontaneous resolution of HCV infection. METHODS: A cross-sectional study was conducted among 1143 HIV patients under follow-up in a HIV/AIDS outpatient reference center of the Brazilian public health system. From 357 anti-HCV positive patients, a consecutive sample of 227 individuals HCV treatment-naïve was interviewed and 207 was tested for HCV-RNA and genotypes. RESULTS: Anti-HCV was detected in 357 patients (31.2%). HCV-RNA was undetectable in 16.4% of 207 anti-HCV positive individuals. Genotype 1 was diagnosed in 81.5% of the sample, genotype 2 in 1.7% and genotype 3 in 16.2%. Male gender was the unique characteristic associated with higher prevalence of genotype 1 HCV. CONCLUSIONS: Co-infection by HCV is frequent among patients with HIV in our State, and it is particularly high the infection by HCV genotype 1. Further investigation is necessary to explain the important regional variation in the proportion of infection by the different HCV genotypes and to better understand rates of spontaneous HCV clearance.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis.

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55%) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3%) vs. 8 (17%) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Low-dose adrenocorticotropin test in patients with the Acquired Immunodeficiency Syndrome

Adrenocortical insufficiency is a serious complication of AIDS. Usually, integrity of the hypothalamo-pituitary-adrenal (HPA) axis in AIDS patients is assessed by measuring basal cortisol levels and cortisol response to 250 µg of ACTH. Recent studies suggest that a lower ACTH dose increases the sensitivity of the procedure. In the present study, we investigated the prevalence of adrenal hypofunction in AIDS patients using a low-dose ACTH test (1 µg), evaluated the clinical characteristics that might suggeest this diagnosis, and the diseases and/or drugs that could be associated with it. We prospectively evaluated 63 very ill AIDS patients and 16 normal controls. A standard examination assessed the presence of signs and symptoms of adrenal insufficiency. Blood samples were colleted before and 30 and 40 minutes after an injection of 1 µg 1-24 ACTH. No opportunistic disease, signs, symptoms or drugs were associated with an abnormal cortisol response to ACTH. The lowest stimulated cortisol level in the contol group was 18.5 µg/dL; cortisol level (greather or equal) 18 µg/dL were taken to indicate a normal HPA axis. Test results revealed that 12/63 AIDS patients (19 percent) had an abnormal HPA axis. With these data in mind, we suggest a prospective adrenal function evaluation of all severely ill AIDS patients.

Clinical and endoscopic aspects in the evolution of patients with bleeding peptic ulcer: a cohort study

BACKGROUND: Bleeding ulcers are a major problem in public health and represent approximately half of all the cases of upper gastrointestinal hemorrhage in the United States. This study aims to determine the prognostic value of factors such as clinical history, laboratory and endoscopic findings in the occurrence of new episodes of bleeding in patients who have upper gastrointestinal hemorrhage caused by gastric or duodenal peptic ulcer. METHODS: A cohort study with 94 patients was designed to investigate prognostic factors to the occurrence of new episodes of bleeding. RESULTS: From the 94 patients studied, 88 did not present a new bleeding episode in the 7 days following hospital admission. The incidence of rebleeding was significantly higher in those patients with hemoglobin < 6 g/dL at the admission (P = 0.03, RR = 6.2). The localization of the ulcers in bulb was positively associated to rebleeding (P = 0.003). The rebleeding group needed a greater number of units transfunded (P = 0.03) and the time of hospitalization was longer than the time of the hemostasia group (P = 0.0349). CONCLUSIONS: The identification of patients with risk of death by bleeding peptic ulcer remains as a challenge, once few factors are capable of predicting the severity of the evolution. The identification of such factors will alow the choice of the better therapeutic conduct improving the diagnosis and decreasing the rate of rebleeding and the mortality