The Burden of Untreated HCV Infection in Hospitalized Inmates: a Hospital Utilization and Cost Analysis.

Hepatitis C virus (HCV) is highly prevalent in incarcerated populations. The high cost of HCV therapy places a major burden on correctional system healthcare budgets, but the burden of untreated HCV is not known. We investigated the economic impact of HCV through comparison of length of stay (LOS), frequency of 30-day readmission, and costs of hospitalizations in inmates with and without HCV using a 2004-2014 administrative claims database. Inmates with HCV had longer LOS, higher frequency of 30-day readmission, and increased cost of hospitalizations. Costs were higher in inmates with HCV even without advanced liver disease and in inmates with HIV/HCV compared to HCV alone. We conclude that although HCV treatment may not avert all of the observed increases in hospitalization, modest reductions in hospital utilization with HCV cure could help offset treatment costs. Policy discussions on HCV treatment in corrections should be informed by the costs of untreated HCV infection.

Institutionally chartered Data and Safety Monitoring Boards: structured approaches to assuring participant safety in clinical research.

Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually, academic health centers also created institutionally focused trial monitoring mechanisms. The basic general principles that define traditional DSMBs extend to the institutional level. The primary responsibilities are assuring safety of the participants, preserving the integrity of the trial, and ensuring the reliability of the results. Institutionally chartered DSMBs meet these responsibilities but usually have fewer members, have a structure specific to the needs of the trial, are more focused and/or have different scope reviewing smaller, single site, higher risk, and investigator-initiated studies and are flexible to accommodate institution-specific requirements and approaches. Their purpose is to meet the responsibilities of oversight for safety and data integrity, ensure proper study design, rigor and conduct, as well as provide statistical support appropriate to the setting of the research. Academic health centers should recognize the importance and existence of institution level safety and data monitoring and provide support as much as possible. Investigators should have sufficient resources available to assemble DSMBs. The Clinical and Translational Science Awards Collaborative DSMB Workgroup provides an online manual to assist investigators.

"I'm not gonna be able to do anything about it, then what's the point?": A broad group of stakeholders identify barriers and facilitators to HCV testing in a Massachusetts jail.

BACKGROUND: Despite national guidelines promoting hepatitis C virus (HCV) testing in prisons, there is substantial heterogeneity on the implementation of HCV testing in jails. We sought to better understand barriers and opportunities for HCV testing by interviewing a broad group of stakeholders involved in HCV testing and treatment policies and procedures in Massachusetts jails. METHODS: We conducted semi-structured interviews with people incarcerated in Middlesex County Jail (North Billerica, MA), clinicians working in jail and community settings, corrections administrators, and representatives from public health, government, and industry between November 2018-April 2019. RESULTS: 51/120 (42%) of people agreed to be interviewed including 21 incarcerated men (mean age 32 [IQR 25, 39], 60% non-White). Themes that emerged from these interviews included gaps in knowledge about HCV testing and treatment opportunities in jail, the impact of captivity and transience, and interest in improving linkage to HCV care after release. Many stakeholders discussed stigma around HCV infection as a factor in reluctance to provide HCV testing or treatment in the jail setting. Some stakeholders expressed that stigma often led decisionmakers to estimate a lower "worth" of incarcerated individuals living with HCV and therefore to decide against paying for HCV testing.". CONCLUSION: All stakeholders agreed that HCV in the jail setting is a public health issue that needs to be addressed. Exploring stakeholders' many ideas about how HCV testing and treatment can be approached is the first step in developing feasible and acceptable strategies.

Factors associated with serum retinol, alpha-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chronic hepatitis C, and drug use.

The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C infection was associated with lower serum retinol (-8.2 microg/dl, P < 0.0001), alpha-tocopherol (-0.10 ln microg/dl, P = 0.024), and carotenoids (-19.8 microg/dl, P < 0.0001). HIV infection was associated with lower selenium (-6.1 microg/l, P = 0.028). Elevated triglycerides in HIV infection were associated with higher serum retinol and alpha-tocopherol. Drug use was not independently associated with micronutrient alterations. We conclude that hepatitis C is an important determinant of low serum micronutrients, and should be considered in any nutritional assessment of HIV infected populations. As the safety of micronutrient supplementation is not established, policy for appropriate HIV clinical care should distinguish between populations with and without hepatitis coinfection.

Via media: Role and responsibilities of the independent safety officer.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

Cystatin C and creatinine in an HIV cohort: the nutrition for healthy living study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons have an increased risk of chronic kidney disease (CKD). Serum creatinine level may underestimate the prevalence of CKD in subjects with decreased lean body mass or liver disease. Level of serum cystatin C, an alternative kidney function marker, is independent of lean body mass. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 250 HIV-infected subjects on highly active antiretroviral therapy in the Nutrition for Healthy Living (NFHL) cohort; 2,628 National Health and Nutrition Examination Survey (NHANES) 2001-2002 subjects. PREDICTORS & OUTCOMES: Comparison of serum creatinine levels in NFHL to those in NHANES subjects; comparison of CKD in NFHL subjects ascertained using serum creatinine versus cystatin C levels. MEASUREMENTS: Standardized serum creatinine, serum cystatin C, glomerular filtration rate (GFR) estimated from serum creatinine and cystatin C levels. RESULTS: Creatinine levels were lower in NFHL than NHANES subjects despite greater rates of hepatitis, diabetes, and drug use (mean difference, -0.18 mg/dL; P < 0.001 adjusted for age, sex, and race). Of NFHL subjects, only 2.4% had a creatinine-based estimated GFR less than 60 mL/min/1.73 m(2), but 15.2% had a cystatin-based estimated GFR less than 60 mL/min/1.73 m(2). LIMITATIONS: GFR was estimated rather than measured. Other factors in addition to GFR may affect creatinine and cystatin C levels. Measurements of proteinuria were not available. CONCLUSIONS: Serum creatinine levels may overestimate GFRs in HIV-infected subjects. Kidney disease prevalence may be greater than previously appreciated.

The impact of cirrhosis on CD4+ T cell counts in HIV-seronegative patients.

BACKGROUND: Studies of the progression liver fibrosis in human immunodeficiency virus (HIV) and hepatitis C virus-coinfected patients suggest that cirrhosis is associated with immunosuppression, as measured by low absolute CD4(+) T cell counts. However, we hypothesized that, in patients with advanced liver disease, low CD4(+) T cell counts may occur secondary to portal hypertension and splenic sequestration, regardless of the presence or absence of HIV infection. METHODS: Sixty HIV-seronegative outpatients with cirrhosis were enrolled during the period 2001-2003 in a prospective, cross-sectional study of the association between liver disease and CD4(+) T cell counts and percentages. Demographic characteristics, liver disease-related characteristics, and laboratory results--including CD4(+) T cell parameters--were collected. RESULTS: A total of 39 patients (65%) had a low CD4(+) T cell count; 26 patients (43%) and 4 patients (7%) had CD4(+) T cell counts <350 and <200 cells/mm(3), respectively. Abnormal CD4(+) T cell counts were associated with splenomegaly (P=.03), thrombocytopenia (P=.002), and leukopenia (P<.001). The percentage of CD4(+) T cells was normal in 95% of patients who had a low absolute CD4(+) T cell count. CD4(+) T cell counts were significantly lower among cirrhotic patients than among 7638 HIV-seronegative historic control subjects without liver disease. CONCLUSIONS: Cirrhosis is associated with low CD4(+) T cell counts in the absence of HIV infection. Discordance between low absolute CD4(+) T cell counts and normal CD4(+) T cell percentages may be attributable to portal hypertension and splenic sequestration. Our findings have significant implications for the use and interpretation of absolute CD4(+) T cell counts in HIV-infected patients with advanced liver disease.

"Tweak Your Order Set!" Implementation of Modified Laboratory Order Set Improves Hepatitis C Virus Screening Rates in People Living With Human Immunodeficiency Virus.

There are several barriers to annual hepatitis C virus antibody (HCVAb) testing, including lack of provider knowledge of the changing HCV epidemic and provider underestimation of a patient's risk. We identified low rates of testing for HCVAb in people living with human immunodeficiency virus (HIV) in our outpatient HIV Infectious Diseases clinic, and we developed a quality improvement project to increase rates of HCVAb screening.

Hepatitis C Screening in People With Human Immunodeficiency Virus: Lessons Learned From Syphilis Screening.

Background. The incidence of hepatitis C virus (HCV) infection is increasing in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). New guidelines recommend annual screening for HCV, similar to recommendations for syphilis screening with rapid plasma reagin (RPR). Methods. This study compares the frequency of repeat HCV antibody (Ab) testing to repeat RPR testing in a retrospective chart review of 359 HCVAb-negative people living with HIV (PLWH) observed in an Infectious Diseases clinic. Patients were classified into risk groups based on sexual risk factors. Results. Although 85% of PLWH had repeat syphilis screening, less than two thirds had repeat HCVAb screening. The MSM status was associated with increased HCVAb and RPR testing (adjusted odds ratio, 2.6 and 5.9, respectively). Seven persons had incident HCV infection: 3 were MSM, and 4 had symptoms or abnormal laboratory results to prompt testing. Conclusions. Failure to find incident HCV infection in PLWH represents missed opportunities to cure HCV infection and prevent progressive liver disease. Further quality improvement studies are necessary to develop physician-focused interventions to increase HCV screening rates in PLWH.

Increasing Infectious Endocarditis Admissions Among Young People Who Inject Drugs.

People who inject drugs (PWID) are at risk for infective endocarditis (IE). Hospitalization rates related to misuse of prescription opioids and heroin have increased in recent years, but there are no recent investigations into rates of hospitalizations from injection drug use-related IE (IDU-IE). Using the Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) dataset, we found that the proportion of IE hospitalizations from IDU-IE increased from 7% to 12.1% between 2000 and 2013. Over this time period, we detected a significant increase in the percentages of IDU-IE hospitalizations among 15- to 34-year-olds (27.1%-42.0%; P < .001) and among whites (40.2%-68.9%; P < .001). Female gender was less common when examining all the IDU-IE (40.9%), but it was more common in the 15- to 34-year-old age group (53%). Our findings suggest that the demographics of inpatients hospitalized with IDU-IE are shifting to reflect younger PWID who are more likely to be white and female than previously reported. Future studies to investigate risk behaviors associated with IDU-IE and targeted harm reduction strategies are needed to avoid further increases in morbidity and mortality in this rapidly growing population of young PWID.

Understanding the role of HIV load in determining weight change in the era of highly active antiretroviral therapy.

BACKGROUND: In this prospective cohort study, we determined the relationship between human immunodeficiency virus (HIV) RNA load and body weight in patients with HIV infection. METHODS: Repeated-measures analysis was restricted to patients with >or=2 study visits, 4-9-month intervals between study visits, and complete data on virus load, resting energy expenditure (REE), and highly active antiretroviral therapy (HAART). The outcome was change in body weight across study intervals. The main predictor was virus load. Separate analyses were performed for weight change in patients receiving and patients not receiving HAART. RESULTS: The eligible sample consisted of 318 participants associated with 1886 study intervals. Sixty-one patients (19%) were women, and 173 (54%) were undergoing HAART at the time of enrollment. There was a significant interaction (P=.01) between virus load and HAART use. In the absence of HAART, each log(10) increase in virus load was associated with a 0.92-kg decrease in body weight (P=.003), but during HAART, virus load was not significantly associated with weight change. During HAART, a CD4(+) cell count decrease of 100 cells/mm(3), rather than a change in the virus load, was associated with a 0.35-kg decrease in body weight (P<.001). REE was independently associated with weight change in both models (P<.001). CONCLUSIONS: Patients with HIV infection who are losing weight and are not taking HAART should be considered for HAART. Patients who are already receiving HAART and have unsuppressed virus loads may benefit virologically from an intensified regimen, because such a regimen may lead to complete suppression if there is an accompanying increase in CD4(+) cell counts. Further research is needed to understand the strong independent effect of changes in REE among patients receiving and patients not receiving HAART.

Dietary intake in HIV-positive persons with and without malabsorption.

This review examines the relationship among malabsorption, diarrhea, dietary intake, and body composition in an outpatient cohort of individuals with HIV infection. Twenty-three percent of the participants had malabsorption, which was not associated with the presence of current or chronic diarrhea. In this "outpatient" HIV cohort with a mean body-mass index (BMI) of 25 kg/m2, the presence of malabsorption did not have adverse nutritional outcomes in terms of body weight, lean body mass, hemoglobin, or albumin. The diets of those with or without malabsorption did not meet the goals of the Dietary Guidelines for Americans. Median dietary intake was high in percentage of total fat and saturated fat and low in total fiber intake and some key micronutrients.

Assessment of nutritional status, body composition, and human immunodeficiency virus-associated morphologic changes.

Nutritional status should be assessed at regular intervals as part of management of human immunodeficiency virus (HIV) infection. The simplest approach to assessment is serial weight measurement. A comprehensive nutritional assessment includes (1) anthropometric measurements of body composition; (2) biochemical measurements of serum protein, micronutrients, and metabolic parameters; (3) clinical assessment of altered nutritional requirements and social or psychological issues that may preclude adequate intake; and (4) measurement of dietary intake. Techniques for measuring body composition of fat and lean body mass include anthropometry and bioelectric impedance analysis. Other techniques, including dual X-ray absorptiometry (DXA), hydrodensitometry, total body potassium measurement, and cross-sectional computed tomography or magnetic resonance imaging are available in research centers. Anthropometry, including waist-hip ratios, regional DXA, and cross-sectional imaging, is best for detecting morphologic changes associated with fat redistribution syndrome. Nutritional assessment and intervention in children with HIV can help to prevent stunted growth and development.

Effect of dietary intake and protease inhibitors on serum vitamin B12 levels in a cohort of human immunodeficiency virus-positive patients.

The dietary intake of micronutrients and serum micronutrient status have been topics of concern in relation to human immunodeficiency virus (HIV) progression. Most data, however, were collected prior to the introduction of protease inhibitors (PIs). We analyzed dietary intake and serum values of vitamin B(12), including the effect of PIs, in a cohort of persons with HIV infection. During intervals with no PI use, each 1 microg/day increase in B(12) intake was associated with a 1.06 pg/mL increase in serum B(12) levels. However, during intervals with PI use, each 1 microg/day increase in intake was associated with only a 0.12 increase in serum B(12) levels. Adequate serum B(12) levels (>350 pg/mL) cannot be assumed even in the presence of PIs, and dietary supplementation may not be adequate to significantly increase serum B(12) levels. Serum B(12) levels should be determined yearly in persons with HIV infection, regardless of whether they are receiving PI treatment.

Difficulty swallowing and lack of receipt of highly active antiretroviral therapy predict acute weight loss in human immunodeficiency virus disease.

In human immunodeficiency virus (HIV) disease, symptoms of underlying illness may promote weight loss through decreased caloric intake, increased metabolic needs, or nutrient malabsorption. We evaluated disease symptoms as predictors of acute weight loss (i.e., loss of > or =5% of weight). HIV-infected men and women (n=415) were telephoned every 5 weeks to obtain information about weight and recent symptoms. Weight change between each pair of consecutive calls (telephone intervals, 2814) was calculated. Acute weight loss occurred across 4.5% of intervals and among 24% of individuals. Patients reported > or =1 symptom before 58% of telephone intervals. The most common symptoms or symptom complexes before intervals were diarrhea (21% of patients), anorexia (17%), upper respiratory symptoms (16%), skin symptoms (12%), and abdominal pain (12%). Trouble swallowing (6%) and oral symptoms (7%) were less common. Risk of acute weight loss was significantly increased when oral symptoms or trouble swallowing were present, and it was decreased when highly active antiretroviral therapy (HAART) was used or when diarrhea was not present. Even when HAART is being administered, clinicians should remain vigilant regarding weight loss, oral symptoms, and trouble swallowing.

Weight loss and body-composition changes in men and women infected with HIV.

BACKGROUND: The nature of body-composition changes in HIV-associated weight loss is unclear. OBJECTIVE: We examined the relation between the initial percentage of body fat and the composition of weight loss in men and women with HIV infection. DESIGN: HIV-positive adults were seen at semiannual clinic visits, at which time weight, fat, and fat-free mass were determined. The unit of analysis was the person-interval. RESULTS: Five hundred fifty-one persons contributed 2266 intervals of data, of which 311 (14%) were intervals in which weight loss was >/= 5% of initial (start of interval) weight. Of these, 208 (67%) intervals met the criteria for analysis (123 from men and 85 from women). Loss of fat-free mass was dependent on the initial percentage of body fat in the men with < 32% body fat. A plot of the initial percentage of body fat compared with loss of fat-free mass (kg) suggested a nonlinear relation over the range of body fat examined. There was no clear relation between the initial percentage of body fat and loss of fat-free mass in the women. CONCLUSIONS: In men with HIV-associated weight loss, the weight lost as fat-free mass depends on the initial percentage of body fat at low levels of body fat but appears to be independent of initial percentage of body fat at high levels of body fat. In women with HIV-associated weight loss who have normal-to-high body fat stores, loss of fat-free mass is independent of the initial percentage of body fat.

Nutrient intake and body weight in a large HIV cohort that includes women and minorities.

OBJECTIVE: Evaluate the baseline nutrient intake of an HIV positive population that includes significant representation from women and minorities, and determine the relationship between state of disease and nutritional intake. DESIGN: Baseline data from a prospective study (Nutrition for Healthy Living). SUBJECTS: Individuals with HIV in the Boston and Rhode Island area (n = 516); 25% were women and 30% were minorities. METHODS: Nutrient intakes from 3-day food records, which included vitamin/mineral supplements, were estimated by gender and nonwhite vs white categories, after grouping by CD4 lymphocyte counts. STATISTICAL ANALYSES: Spearman correlation coefficients, Wilcoxon signed rank test, Wilcoxon rank sum test, chi2 test, and restricted cubic spline model were used for data analyses as indicated. RESULTS: Macronutrient but not micronutrient intake was statistically and inversely associated with decreasing CD4 cell counts. The median intake of micronutrients was higher in the study sample compared with the same age and gender group in NHANES III data; however, 25% to 35% of the women in our study sample had dietary intakes of less than 75% of the DRIs for vitamins A, C, E and B-6, and iron and zinc. White men had statistically higher values of all micronutrients compared with nonwhite men. Body mass index for men and women ranged from 23 to 25. CONCLUSIONS/APPLICATIONS: Median values for micronutrient intake from food plus vitamin/mineral supplements were adequate in the overall population studied, but a large percent of women and minorities had inadequate nutrient intakes and would benefit from dietary assessment and counseling.

Metabolic syndrome predicts all-cause mortality in persons with human immunodeficiency virus.

We examined the association between metabolic syndrome (MS) and its individual defining criteria on all-cause mortality in human immunodeficiency virus (HIV)-infected persons. We used data from 567 HIV-infected participants of the Nutrition for Healthy Living study with study visits between 9/1/2000 and 1/31/2004 and determined mortality through 12/31/2006. MS was defined using modified National Cholesterol Education Program guidelines. Cox proportional hazards for all-cause mortality were estimated for baseline MS status and for its individual defining criteria. There were 83 deaths with median follow-up of 63 months. Baseline characteristics associated with increased risk of mortality were: older age in years (univariate hazard ratio [HR] 1.04, p<0.01), current smoking (HR 1.99, p=0.02), current heroin use (HR 1.97, p=0.02), living in poverty (HR 2.0, p<0.01), higher mean HIV viral load (HR 1.81, p<0.01), and having a BMI <18 (HR 5.84, p<0.01). For MS and its criteria, only low HDL was associated with increased risk of mortality on univariate analysis (HR 1.84, p=0.01). However, metabolic syndrome (adjusted HR 2.31, p=0.02) and high triglycerides (adjusted HR 3.97, p<0.01) were significantly associated with mortality beyond 36 months follow-up. MS, low HDL, and high triglycerides are associated with an increased risk of mortality in HIV-infected individuals.