Shashwatee Bagchi

Elbasvir/grazoprevir for treatment of chronic hepatitis C virus infection

Hepatitis C is the leading cause of progressive liver fibrosis worldwide and results in cirrhosis, liver cancer, liver failure and death. Successful treatment for hepatitis C virus (HCV) has rapidly evolved in recent years to a well-tolerated, highly efficacious all-oral therapy. Elbasvir/grazoprevir (Zepatier) is the newest of the oral combinations of HCV direct-acting agents that was approved by the US Federal Drug Administration. This review focuses on the pharmacology, mechanism of action and clinical trial data that support the use of this new combination treatment for HCV infection. The data suggest that Zepatier offers an excellent treatment efficacy, safety and tolerability in HCV treatment naïve and experienced patients and those with and without cirrhosis across multiple genotypes. Also, it has the selective advantage of safety and efficacy in patients with renal disease, especially in those with end-stage renal disease and/or hemodialysis patients.

Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review

Abstract Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.

Review of Cardiovascular Disease in HIV-Infected Women

Rates of coronary heart disease (CHD) are over twice as high in younger HIV-infected patients compared to uninfected patients, but most of these studies were conducted in men or in predominantly male cohorts. In the general population, the death rate from CHD has decreased among men, but continues to increase in women. It is unclear if the same increased rate of deaths due to CHD exist in HIV-infected women, and whether rates or risk of CHD differ between HIV-infected men and women, and between seropositive and seronegative women. We reviewed the literature on the rates of cardiovascular events and surrogate measures of atherosclerosis or CHD risk in HIV-infected women. We also reviewed rates of metabolic disease and other markers of inflammation and immune activation that could contribute to increased cardiovascular risk. We found that HIV-infected women have increased rates of acute myocardial infarctions and ischemic strokes compared to HIV-uninfected women and likely HIV-infected men despite women being projected to have lower CHD risk based on Framingham risk scores. Studies assessing CHD risk by measuring anatomical or physiological measures of subclinical atherosclerosis have reported mixed results, and there are no well-validated risk assessment tools or surrogate measures of subclinical CHD among HIV-infected patients to help identify high-risk women for targeting intensive preventive measures. Potential explanations for the increased rates of CHD and subclinical atherosclerosis may be partly explained by increased levels of inflammation and immune activation in HIV-infected women despite virological suppression on antiretroviral therapy. It appears unlikely that disproportionate representation of traditional CHD risk factors and metabolic indices among HIV-infected women can explain well the observed increased rates of CHD. Future studies that include large numbers of HIV-infected women with extended follow-up periods using surrogate measure of CVD and investigating pathogenic mechanisms underlying these observations are urgently needed.

Cardiovascular Disease Risk Assessment Tools in HIV-Infected Patients - AreThey Adequate?

Cardiovascular disease (CVD) has become one of the leading causes of morbidity and mortality among HIVinfected patients with seropositive patients developing CVD at higher rates than seronegative patients. Therefore, it is critical to have inexpensive, non-invasive assessment tools for CVD risk assessment in HIV-infected patients. Nearly all CVD risk assessment tools were derived from the general population, and their ability to predict CVD in the HIV population has been variable. In order to more accurately predict CVD risk in HIV-infected patients, a new CVD risk assessment tool derived from the HIV population that accounted for factors specific to HIV infection, disease course, and/or sequelae of treatment with antiretroviral therapy is needed. An improved CVD risk assessment tool for HIVinfected patients will help determine which patients would most benefit from primary prevention strategies.

Underutilization of statins for prevention of cardiovascular disease among primarily African-American HIV-infected patients.

Background: Studies have consistently demonstrated that statin therapy reduces CHD-related mortality, but HIVinfected individuals are frequently undertreated for hyperlipidemia. Therefore, we sought to: 1. determine whether the numbers of patients recommended for statin therapy differed using the 2004 and 2013 guidelines; 2. evaluate the proportion of recommended patients who were actually receiving statins; and 3. evaluate the factors associated with statin prescription. Methods: Conducted cross-sectional analysis of a retrospective cohort. 100 patients receiving care at an academic inner-city HIV clinic in 2008 were reviewed. The atherosclerotic vascular disease (ASCVD) risk score was calculated using the 2013 Pooled Cohort Equation and the 2004 and 2013 guidelines were applied to evaluate numbers of patients recommended for statin therapy. Proportions were used to report patients receiving statins among those who were recommended for treatment and several unadjusted logistic regression analyses were performed to identify factors associated with utilization of statins in recommended patients. Results: 81 participants were included in the final analysis. Substantially larger numbers of HIV-infected individuals were recommended to receive statin therapy for CHD risk reduction when applying the 2013 guidelines compared to the 2004 guidelines, but less than half received statins for primary prevention as recommended. Prescription of statins was not associated with either ASCVD risk score or many traditional CHD risk factors. Diabetes mellitus was associated with increased odds of receiving statin therapy whereas hepatitis C co-infection and current smoking status were associated with decreased odds of receiving statins. Conclusions: There is an increased, large and unmet need to increase statin use for prevention of CHD. Underutilization of statins was most pronounced among HIV-hepatitis C co-infected patients and HIV-infected smokers.

Global Burden of Atherosclerotic Cardiovascular Disease in People Living with the Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis

Background: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV. Methods: We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV. Results: In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8–83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68–2.77). Over the past 26 years, the global population–attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%–0.56%) to 0.92% (95% CI, 0.55%–1.41%), and DALYs increased from 0.74 (95% CI, 0.44–1.16) to 2.57 (95% CI, 1.53–3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43–1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23–0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho. Conclusions: People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions. Clinical Trial Registration: URL: https://www.crd.york.ac.uk/prospero. Unique identifier: CRD42016048257.

Factors associated with high cardiovascular risk in a primarily African American, urban HIV-infected population

Objective: To determine factors associated with increased risk of developing cardiovascular disease in a high-risk patient population. Design: Cross-sectional analysis of a retrospective cohort study. Methods: One-hundred patients at an inner city HIV clinic in 2008 were reviewed. The atherosclerotic vascular disease risk score was calculated using the Pooled Cohort Equation. Chi-square test was performed to identify associations of potential risk factors with elevated atherosclerotic vascular disease risk. Results: Eighty-one participants were included in the final analysis. In total, 95.1% were African American, and 38.3% were women. The median atherosclerotic vascular disease risk score was 8.8% and 8.1% in 2008 and 2012, respectively. The medical co-morbidities associated with increased atherosclerotic vascular disease risk were hepatitis C infection (X2 = 3.93; p value = 0.048), elevated triglycerides levels (X2 = 4.0; p value = 0.046), and low albumin (X2 = 4.65; p value = 0.031). There were a higher number of women with known atherosclerotic vascular disease despite lower median atherosclerotic vascular disease risk score compared to men. Conclusion: An elevated risk of developing cardiovascular disease persists in high-risk demographic groups of the HIV epidemic even in the current HIV era. There is an unexplained gender disparity and some non-traditional risk factors not accounted for in the Pooled Cohort Equation may be contributing to the excess cardiovascular disease risk observed among HIV-infected patients.

Erratum to: Elbasvir/grazoprevir for treatment of chronic hepatitis C virus infection.

In the original publication, some entries in Table 2 are incorrect. The corresponding text under the subsection, Phase 3 studies, paragraph 6 in page 7 is also incorrectly published as GT subtype SVR12 rates were 60% for GT1a, 40% for GT1b, 13% for GT4, and 1% for GT6 infected patients. It should read as (GT1a 94%, GT1b 95%, GT4 96%, and GT6 100%). The corrected version of Table 2 is provided below.