Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy

Background: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining Suppression of plasma HIV RNA less than 400 copies/ml. Methods: Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout. Results: At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log(10) - copies/ml versus 9.27 log(10) copies/ml for placebo, and at week 48, it was 4.79log(10) copies/ml versus 5.63log(10) copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log(10) copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34%. of patients (versus 8% for placebo, P=0.08)At 48 weeks, mean change in HBV DNA reached -4.20log(10) copies/ml inpatients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell Counts were identified. Conclusion: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Preliminary Results from TOPAZ-III, A Phase 3b Study Evaluating the Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir +/- Ribavirin in Naive or Experienced Adults in Brazil with HCV Genotype 1 Infection and Advanced Fibrosis/Cirrhosis

Univ Sao Paulo, Sch Med, Dept Gastroenterol, Sao Paulo, BrazilCtr Referencia & Treinamento DST AIDS, Sao Paulo, BrazilAbbVie Inc, N Chicago, IL USANatl Inst Infect Dis FIOCRUZ, Rio De Janeiro, BrazilUniv Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Gastroenterol & Hepatol Unit, Porto Alegre, RS, BrazilUniv Fed Estado Rio de Janeiro UNIRIO, Coll Med & Surg, Dept Internal Med, Rio De Janeiro, BrazilUniv Sao Paulo, Sch Med, Dept Infect Dis, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Gastroenterol, Sao Paulo, BrazilUniv Sao Paulo, Ribeirao Preto Sch Med, Dept Med, Div Gastroenterol, Sao Paulo, BrazilDepartment of Gastroenterology, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, BrazilWeb of Scienc

Effectiveness of chlorthalidone plus amiloride for the prevention of hypertension the PREVER-Prevention Randomized Clinical Trial

Background-—Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. Methods and Results-—This randomized, parallel, double-blind, placebo-controlled trialwas conducted in 21 Brazilian academicmedical centers. Participants with prehypertensionwho were aged 30 to70 years andwho did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with358 allocated to placebo (hazard ratio 0.56, 95%CI 0.38–0.82), resulting in a cumulative incidence of11.7% in the diuretic arm versus 19.5% in the placebo arm(P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions-—A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension

Effectiveness of chlorthalidone plus amiloride for the prevention of hypertension the PREVER-Prevention Randomized Clinical Trial

Background-—Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. Methods and Results-—This randomized, parallel, double-blind, placebo-controlled trialwas conducted in 21 Brazilian academicmedical centers. Participants with prehypertensionwho were aged 30 to70 years andwho did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with358 allocated to placebo (hazard ratio 0.56, 95%CI 0.38–0.82), resulting in a cumulative incidence of11.7% in the diuretic arm versus 19.5% in the placebo arm(P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions-—A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension

Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study

Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013.Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data.Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insuffi cient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively).Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections