Mathematical Modeling of Hepatitis C Prevalence Reduction with Antiviral Treatment Scale-Up in Persons Who Inject Drugs in Metropolitan Chicago

Background/Aim

New direct-acting antivirals (DAAs) provide an opportunity to combat hepatitis C virus (HCV) infection in persons who inject drugs (PWID). Here we use a mathematical model to predict the impact of a DAA-treatment scale-up on HCV prevalence among PWID and the estimated cost in metropolitan Chicago.

Methods

To estimate the HCV antibody and HCV-RNA (chronic infection) prevalence among the metropolitan Chicago PWID population, we used empirical data from three large epidemiological studies. Cost of DAAs is assumed $50,000 per person.

Results

Approximately 32,000 PWID reside in metropolitan Chicago with an estimated HCV-RNA prevalence of 47% or 15,040 cases. Approximately 22,000 PWID (69% of the total PWID population) attend harm reduction (HR) programs, such as syringe exchange programs, and have an estimated HCV-RNA prevalence of 30%. There are about 11,000 young PWID (<30 years old) with an estimated HCV-RNA prevalence of 10% (PWID in these two subpopulations overlap). The model suggests that the following treatment scale-up is needed to reduce the baseline HCV-RNA prevalence by one-half over 10 years of treatment [cost per year, min-max in millions]: 35 per 1,000 [$50-$77] in the overall PWID population, 19 per 1,000 [$20-$26] for persons in HR programs, and 5 per 1,000 [$3-$4] for young PWID.

Conclusions

Treatment scale-up could dramatically reduce the prevalence of chronic HCV infection among PWID in Chicago, who are the main reservoir for on-going HCV transmission. Focusing treatment on PWID attending HR programs and/or young PWID could have a significant impact on HCV prevalence in these subpopulations at an attainable cost.     

Racial Differences in Left Atrial Size: Results from the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Whites have an increased risk of atrial fibrillation (AF) compared to Blacks. The mechanism underlying this association is unknown. Left atrial (LA) size is an important AF risk factor, and studies in older adults suggest Whites have larger LA diameters. However, because AF itself causes LA dilation, LA size differences may be due to greater subclinical AF among older Whites. We therefore assessed for racial differences in LA size among young adults at low AF risk. The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled White and Black participants between 18 and 30 years of age. LA diameter was measured in a subset of participants using echocardiography at Year 5 (n = 4,201) and Year 25 (n = 3,373) of follow up. LA volume was also assessed at Year 5 (n = 2,489). Multivariate linear regression models were used to determine the adjusted association between race and LA size. In unadjusted analyses, mean LA diameter was significantly larger among Blacks compared to Whites both at Year 5 (35.5 ± 4.8 mm versus 35.1 ± 4.5 mm, p = 0.01) and Year 25 (37.4 ± 5.1 mm versus 36.8 ± 4.9 mm, p = 0.002). After adjusting for demographics, comorbidities, and echocardiographic parameters, Whites demonstrated an increased LA diameter (0.7 mm larger at Year 5, 95% CI 0.3–1.1, p<0.001; 0.6 mm larger at Year 25, 95% CI 0.3–1.0, p<0.001). There was no significant association between race and adjusted Year 5 LA volume. In conclusion, in a young, well-characterized cohort, the larger adjusted LA diameter among White participants suggests inherent differences in atrial structure may partially explain the higher risk of AF in Whites. The incongruent associations between race, LA diameter, and LA volume suggest that LA geometry, rather than size alone, may have implications for AF risk.     

Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV)-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections

ObjectiveThe prevalence of the hepatitis C virus (HCV) remains high amongst people who inject drugs (PWID) and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV.MethodsA dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality), with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC) treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR) rates of 90–100% and increased uptake over varied horizons.ResultsSoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015–2027 ranged from 20–580 and 34–912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection) and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications), with a projected £5.4 million cost saving.ConclusionWhile improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health burden of HCV-related disease.     

Survival of Hepatitis C Virus in Syringes Is Dependent on the Design of the Syringe-Needle and Dead Space Volume

Background

Many people who inject drugs (PWID) use syringes with detachable needles, which have high dead space (HDS). Contaminated HDS blood may substantially contribute to the transmission of HIV, hepatitis C (HCV), and other blood-borne viruses within this population. Newly designed low dead space (LDS) syringe-needle combinations seek to reduce blood-borne virus transmission among PWID. We evaluated the infectivity of HCV-contaminated residual volumes recovered from two LDS syringe-needle combinations.

Methods

We tested two different design approaches to reducing the dead space. One added a piston to the plunger; the other reduced the dead space within the needle. The two approaches cannot be combined. Recovery of genotype-2a reporter HCV from LDS syringe-needle combinations was compared to recovery from insulin syringes with fixed needles and standard HDS syringe-needle combinations. Recovery of HCV from syringes was determined immediately following their contamination with HCV-spiked plasma, after storage at 22°C for up to 1 week, or after rinsing with water.

Results

Insulin syringes with fixed needles had the lowest proportion of HCV-positive syringes before and after storage. HCV recovery after immediate use ranged from 47%±4% HCV-positive 1 mL insulin syringes with 27-gauge ½ inch needles to 98%±1% HCV-positive HDS 2 mL syringes with 23-gauge 1¼ inch detachable needles. LDS combinations yielded recoveries ranging from 65%±5% to 93%±3%. Recovery was lower in combinations containing LDS needles than LDS syringes. After 3 days of storage, as much as 6-fold differences in virus recovery was observed, with HCV recovery being lower in combinations containing LDS needles. Most combinations with detachable needles required multiple rinses to reduce HCV infectivity to undetectable levels whereas a single rinse of insulin syringes was sufficient.

Conclusions

Our study, the first to assess the infectivity of HCV in residual volumes of LDS syringes and needles available to PWID, demonstrates that LDS syringe-needle combination still has the greater potential for HCV transmission than insulin syringes with fixed needles. Improved LDS designs may be able to further reduce HCV recovery, but based on the designed tested, LDS needles and syringes remain intermediate between fixed-needle syringes and HDS combinations in reducing exposure to HCV.     

Estimating the Number of Persons Who Inject Drugs in the United States by Meta-Analysis to Calculate National Rates of HIV and Hepatitis C Virus Infections

Background

Injection drug use provides an efficient mechanism for transmitting bloodborne viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Effective targeting of resources for prevention of HIV and HCV infection among persons who inject drugs (PWID) is based on knowledge of the population size and disparity in disease burden among PWID. This study estimated the number of PWID in the United States to calculate rates of HIV and HCV infection.

Methods

We conducted meta-analysis using data from 4 national probability surveys that measured lifetime (3 surveys) or past-year (3 surveys) injection drug use to estimate the proportion of the United States population that has injected drugs. We then applied these proportions to census data to produce population size estimates. To estimate the disease burden among PWID by calculating rates of disease we used lifetime population size estimates of PWID as denominators and estimates of HIV and HCV infection from national HIV surveillance and survey data, respectively, as numerators. We calculated rates of HIV among PWID by gender-, age-, and race/ethnicity.

Results

Lifetime PWID comprised 2.6% (95% confidence interval: 1.8%–3.3%) of the U.S. population aged 13 years or older, representing approximately 6,612,488 PWID (range: 4,583,188–8,641,788) in 2011. The population estimate of past-year PWID was 0.30% (95% confidence interval: 0.19 %–0.41%) or 774,434 PWID (range: 494,605–1,054,263). Among lifetime PWID, the 2011 HIV diagnosis rate was 55 per 100,000 PWID; the rate of persons living with a diagnosis of HIV infection in 2010 was 2,147 per 100,000 PWID; and the 2011 HCV infection rate was 43,126 per 100,000 PWID.

Conclusion

Estimates of the number of PWID and disease rates among PWID are important for program planning and addressing health inequities.     

Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Background

Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms.

Methods

In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models.

Results

Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005–0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0–2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11–122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3–0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2–2.5] and 1.4 [1.0–1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0–2.0]).

Conclusion

Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0610-4) contains supplementary material, which is available to authorized users.     

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background

People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed.

Methods and Findings

We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade.

Conclusion

Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID.     

HIV among People Who Inject Drugs in the Middle East and North Africa: Systematic Review and Data Synthesis

Background

It is perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA.

Methods and Findings

This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. Risk of bias in predefined quality domains was described to assess the quality of available HIV prevalence measures. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases.We estimated that there are 626,000 PWID in MENA (range: 335,000–1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10%–15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18%–28% in the last injection), the low levels of condom use (20%–54% ever condom use), the high levels of having sex with sex workers and of men having sex with men (15%–30% and 2%–10% in the last year, respectively), and of selling sex (5%–29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31%–64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics.

Conclusions

Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems. Please see later in the article for the Editors'' Summary     

The Epidemiology of Hepatitis C Virus in the Fertile Crescent: Systematic Review and Meta-Analysis

Objective

To characterize hepatitis C virus (HCV) epidemiology in countries of the Fertile Crescent region of the Middle East and North Africa (MENA), namely Iraq, Jordan, Lebanon, Palestine, and Syria.

Methods

We systematically reviewed and synthesized available records of HCV incidence and prevalence following PRISMA guidelines. Meta-analyses were implemented using a DerSimonian-Laird random effects model with inverse weighting to estimate the country-specific HCV prevalence among the various at risk population groups.

Results

We identified eight HCV incidence and 240 HCV prevalence measures in the Fertile Crescent. HCV sero-conversion risk among hemodialysis patients was 9.2% in Jordan and 40.3% in Iraq, and ranged between 0% and 3.5% among other populations in Iraq over different follow-up times. Our meta-analyses estimated HCV prevalence among the general population at 0.2% in Iraq (range: 0–7.2%; 95% CI: 0.1–0.3%), 0.3% in Jordan (range: 0–2.0%; 95% CI: 0.1–0.5%), 0.2% in Lebanon (range: 0–3.4%; 95% CI: 0.1–0.3%), 0.2% in Palestine (range: 0–9.0%; 95% CI: 0.2–0.3%), and 0.4% in Syria (range: 0.3–0.9%; 95% CI: 0.4–0.5%). Among populations at high risk, HCV prevalence was estimated at 19.5% in Iraq (range: 0–67.3%; 95% CI: 14.9–24.5%), 37.0% in Jordan (range: 21–59.5%; 95% CI: 29.3–45.0%), 14.5% in Lebanon (range: 0–52.8%; 95% CI: 5.6–26.5%), and 47.4% in Syria (range: 21.0–75.0%; 95% CI: 32.5–62.5%). Genotypes 4 and 1 appear to be the dominant circulating strains.

Conclusions

HCV prevalence in the population at large appears to be below 1%, lower than that in other MENA sub-regions, and tending towards the lower end of the global range. However, there is evidence for ongoing HCV transmission within medical facilities and among people who inject drugs (PWID). Migration dynamics appear to have played a role in determining the circulating genotypes. HCV prevention efforts should be targeted, and focus on infection control in clinical settings and harm reduction among PWID.     

Racial disparities in total ankle arthroplasty utilization and outcomes

IntroductionThe objective of this study was to examine the racial disparities in total ankle arthroplasty (TAA) utilization and outcomes.MethodsWe used the National Inpatient Sample (NIS) to study the time-trends. Race was categorized as White and Black. Utilization rates were calculated for the U.S. general population per 100,000. Hospital length of stay, discharge disposition and mortality after TAA were assessed. We used the Cochran Armitage trend test to assess time-trends from 1998 to 2011 and chi-square test to compare TAA utilization. We used analysis of variance or chi-squared test to compare the characteristics of Whites and Blacks undergoing TAA and logistic regression to compare mortality, length of stay and discharge to home versus medical facility.ResultsThe mean ages for Whites undergoing TAA were 62 years and for Blacks was 52 years. Significant racial disparities were noted in TAA utilization rates (/100,000) in 1998, 0.14 in Whites vs. 0.07 in Blacks (P < 0.0001; 2-fold) and in 2011, 1.17 in Whites vs. 0.33 in Blacks (P < 0.0001; 4-fold). Racial disparities in TAA utilization increased significantly from 1998 to 2011 (P < 0.0001). There was a trend towards statistical significance for the difference in the length of hospital stay in Blacks vs. Whites (52.9% vs. 44.3% with length of hospital stay higher than the median; P = 0.08). Differences in the proportion discharged to an inpatient medical facility after TAA, 16.6% Blacks vs. 13.4% Whites, were not significant (P = 0.36).ConclusionsThis study demonstrated significant racial disparities with lower TAA utilization and suboptimal outcomes in Blacks compared to Whites. Further studies are needed to understand the mediators of these disparities and to assess whether these mediators can be targeted to reduce racial disparities in TAA.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0589-2) contains supplementary material, which is available to authorized users.     

HIV,HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

Background

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.

Method

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.

Findings

HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID.

Conclusions

We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.     

Trends in the Population Prevalence of People Who Inject Drugs in US Metropolitan Areas 1992–2007

Background

People who inject drugs (PWID) have increased risk of morbidity and mortality. We update and present estimates and trends of the prevalence of current PWID and PWID subpopulations in 96 US metropolitan statistical areas (MSAs) for 1992–2007. Current estimates of PWID and PWID subpopulations will help target services and help to understand long-term health trends among PWID populations.

Methodology

We calculated the number of PWID in the US annually from 1992–2007 and apportioned estimates to MSAs using multiplier methods. We used four types of data indicating drug injection to allocate national annual totals to MSAs, creating four distinct series of component estimates of PWID in each MSA and year. The four component estimates are averaged to create the best estimate of PWID for each MSA and year. We estimated PWID prevalence rates for three subpopulations defined by gender, age, and race/ethnicity. We evaluated trends using multi-level polynomial models.

Results

PWID per 10,000 persons aged 15–64 years varied across MSAs from 31 to 345 in 1992 (median 104.4) to 34 to 324 in 2007 (median 91.5). Trend analysis indicates that this rate declined during the early period and then was relatively stable in 2002–2007. Overall prevalence rates for non-Hispanic black PWID increased in 2005 as compared to other racial/ethnic groups. Hispanic prevalence, in contrast, declined across time. Importantly, results show a worrisome trend in young PWID prevalence since HAART was initiated – the mean prevalence was 90 to 100 per 10,000 youth in 1992–1996, but increased to >120 PWID per 10,000 youth in 2006–2007.

Conclusions

Overall, PWID rates remained constant since 2002, but increased for two subpopulations: non-Hispanic black PWID and young PWID. Estimates of PWID are important for planning and evaluating public health programs to reduce harm among PWID and for understanding related trends in social and health outcomes.     

Rapid Decline in HCV Incidence among People Who Inject Drugs Associated with National Scale-Up in Coverage of a Combination of Harm Reduction Interventions

Background

Government policy has precipitated recent changes in the provision of harm reduction interventions – injecting equipment provision (IEP) and opiate substitution therapy (OST) – for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID.

Methods and Findings

We used a framework to triangulate different types of evidence: ‘group-level/ecological’ and ‘individual-level’. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1–2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1–20.1) in 2008–09 to 7.3 (3.0–12.9) in 2011–12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11–0.74) and weighted for frequency of injecting (AOR_w 0.05, 95%CI 0.01–0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008–2012.

Conclusions

This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.     

Prevalence,Awareness, Treatment and Influence of Socioeconomic Variables on Control of High Blood Pressure: Results of the ELSA-Brasil Study

High blood pressure (HBP) is the leading risk factor for years of life lost in Brazil. Factors associated with HBP awareness, treatment and control need to be understood better. Our aim is to estimate prevalence, awareness, and types of anti-hypertensive treatment and to investigate the association of HBP control with social position. Data of 15,103 (54% female) civil servants in six Brazilian state capitals collected at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline (2008-2010) were used to estimate prevalence and cross-sectional association of HBP control with education, per capita family income and self-reported race, using multiple logistic regression. Blood pressure was measured by the oscillometric method. 35.8% were classified as presenting HBP; 76.8% of these used anti-hypertensive medication. Women were more aware than men (84.8% v. 75.8%) and more often using medication (83.1% v. 70.7%). Adjusted HBP prevalence was, in ascending order, Whites (30.3%), Browns (38.2%) and Blacks (49.3%). The therapeutic schemes most used were angiotensin-converting enzyme inhibitors, in isolation (12.4%) or combined with diuretics (13.3%). Among those in drug treatment, controlled blood pressure was more likely in the (postgraduate) higher education group than among participants with less than secondary school education (PR = 1.21; 95% CI: 1.14–1.28), and among Asian (PR = 1.21; 95% CI: 1.12–1.32) and ‘Whites (PR = 1.19; 95% CI: 1.12–1.26) compared to Blacks. Socioeconomic and racial inequality—as measured by different indicators—are strongly associated with HBP control, beyond the expected influence of health services access.     

Hepatitis C Viremia Patterns in Incident Hepatitis C Infection and One Year Later in 150 Prospectively Tested Persons Who Inject Drugs

Objectives

To assess HCV viremia levels just before, during and one year after anti-HCV seroconversion in people who inject drugs (PWID).

Methods

PWID enrolling into a needle exchange program in Malmö, Sweden, 1997–2005 constituted the source population. Sera were obtained at enrolment and at approximately 3–4 monthly intervals afterwards, and were initially tested for anti-HIV, HBsAg/anti-HBc and anti-HCV and thereafter for markers previously negative. Seroconversion to anti-HCV had occurred during the study period in 186 out of 332 seronegative subjects. In these anti-HCV seroconverters, quantitative HCV RNA PCR was retrospectively performed on frozen sera to determine viremia levels in the last anti-HCV negative, the first anti-HCV positive and in one year follow-up samples.

Results

Among 150 subjects seroconverting to anti-HCV with samples available from all three defined time-points, eight different patterns of viremia were observed. Spontaneous clearance at one year was noted in 48 cases (32%) and was associated with female gender (p = 0.03, CI 0.17–1.00). In 13 cases HCV-RNA was not detected in any study sample. Among 61 subjects with pre-seroconversion viremia, viral load was significantly higher in the pre-seroconversion samples compared to subsequent samples. For the whole group, viral load declined to undetectable levels at seroconversion in 28% of cases (but with recurrent viremia in 15%).

Conclusions

Different patterns of HCV RNA kinetics were observed among PWID with documented seroconversion to anti-HCV. The frequently observed absence of detectable HCV RNA in the first anti-HCV positive sample (irrespective of subsequent viremia) demonstrates the importance of repeated sampling and RNA testing for determination of the outcome of acute infection.     

Differences in HCV Viral Decline between Low and Standard-Dose Pegylated-Interferon-Alpha-2a with Ribavirin in HIV/HCV Genotype 3 Patients

Background

The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment.

Methods

Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG) included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG) patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model.

Results

One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1∶1.72±0.74 log₁₀ IU/mL versus 1.78±0.67 log₁₀ IU/mL, p = 0.827; week 2∶2.3±0.89 log₁₀ IU/mL versus 3.01±1.02 log₁₀ IU/mL, p = 0.013; week 4∶3.52±1.2 log₁₀ IU/mL versus 4.09±1.1 log₁₀ IU/mL, p = 0.005). The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4.

Conclusions

Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.     

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance

Background

Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress.

Methods and Results

The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5±3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34±10 vs. 39±9%; p = 0.01) but similar LVEF (40±21 vs. 39±18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17±7 vs. 12±6 kPa; p<0.001) corresponding to increased RV end-systolic volume (143±79 vs. 110±36 ml; p = 0.006), myocardial mass (60±21 vs. 53±17 gm; p = 0.04), and PASP (52±18 vs. 41±18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04–1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14–1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69–1.20]; p = 0.5) [model χ² = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001).

Conclusion

Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.     

Body Mass Index and All-Cause Mortality in a Large Prospective Cohort of White and Black U.S. Adults

Remaining controversies on the association between body mass index (BMI) and mortality include the effects of smoking and prevalent disease on the association, whether overweight is associated with higher mortality rates, differences in associations by race and the optimal age at which BMI predicts mortality. To assess the relative risk (RR) of mortality by BMI in Whites and Blacks among subgroups defined by smoking, prevalent disease, and age, 891,572 White and 38,119 Black men and women provided height, weight and other information when enrolled in the Cancer Prevention Study II in 1982. Over 28 years of follow-up, there were 434,400 deaths in Whites and 18,702 deaths in Blacks. Cox proportional-hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI). Smoking and prevalent disease status significantly modified the BMI-mortality relationship in Whites and Blacks; higher BMI was most strongly associated with higher risk of mortality among never smokers without prevalent disease. All levels of overweight and obesity were associated with a statistically significantly higher risk of mortality compared to the reference category (BMI 22.5–24.9 kg/m²), except among Black women where risk was elevated but not statistically significant in the lower end of overweight. Although absolute mortality rates were higher in Blacks than Whites within each BMI category, relative risks (RRs) were similar between race groups for both men and women (p-heterogeneity by race  = 0.20 for men and 0.23 for women). BMI was most strongly associated with mortality when reported before age 70 years. Results from this study demonstrate for the first time that the BMI-mortality relationship differs for men and women who smoke or have prevalent disease compared to healthy never-smokers. These findings further support recommendations for maintaining a BMI between 20–25 kg/m² for optimal health and longevity.     

Prevalence of Hepatitis B Antigen and Antibody in Prostitutes

We investigated the prevalence of hepatitis B antigen (HBAg) and antibody (HBAb) in 293 prostitutes and in 379 pregnant women of similar age and of low socioeconomic level, who served as controls. HBAg was found in 4·4% of prostitutes and 3·4% of controls. The prevalence of HBAb was significantly higher (P <0·001) in prostitutes (56·7%) than in controls (24·5%). The prevalence of HBAb was clearly age-dependent in both groups. Evidence of hepatitis B virus infection significantly increased with the number of years in prostitution. The evidence of increased infection rates among prostitutes and their distribution support the hypothesis that hepatitis B infection is sexually transmitted.     

Hepatitis C Transmission and Treatment in Contact Networks of People Who Inject Drugs

Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from “less-” to “more-frequent” injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.