Andrés Marco

Epidemiological characteristics and predictors of late presentation of HIV infection in Barcelona (Spain) during the period 2001-2009

BackgroundEarly diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09.MethodsDemographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation.ResultsOf the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).ConclusionLate presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.

Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C

BACKGROUND & AIMS We estimated HCV reinfection rate and its associated risk factors in inmates with chronic hepatitis C who had achieved sustained virological response (SVR) after completing combination therapy while in prison. METHODS Individuals who had achieved an SVR after treatment provided from January 2003 to December 2009 at four prisons in Catalonia, had been tested annually for HCV RNA and were in prison during 2010, were invited to complete a questionnaire regarding risk factors for reinfection. Incidence rate was calculated as 100 person-years of follow-up. Risk factors potentially associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression analysis. RESULTS One hundred and nineteen subjects who had achieved an SVR agreed to participate. 98% were male, with a median age of 33.3 ± 6.3 years and 81% had a history of injection drug use (IDU). After a mean follow-up of 1.4 years, HCV reinfection was identified in nine former IDUs, seven with HCV genotype switch, for an overall reinfection rate of 5.27 cases per 100 person-years. Reinfection incidence was significantly higher among active drug users (HR=12.47; 95% CI: 2.90-53.71), HIV co-infected (HR=9.95; 95% CI: 1.73-57.34), and those engaging in more than one risk behaviors after treatment (HR=7.47; 95% CI: 1.19-46.89). CONCLUSIONS HCV reinfection among inmates after successful treatment is high especially in those with ongoing IDU. Preventative interventions at diagnosis and during and after HCV treatment should be strongly reinforced.

Incidence of hepatitis C infection among prisoners by routine laboratory values during a 20-year period.

Background To estimate the incidence of Hepatitis C virus (HCV) and the predictive factors through repeated routine laboratory analyses. Methods An observational cohort study was carried out in Quatre Camins Prison, Barcelona. The study included subjects with an initial negative HCV result and routine laboratory analyses containing HCV serology from 1992 to 2011. The incidence of infection was calculated for the study population and for sub-groups by 100 person-years of follow-up (100 py). The predictive factors were determined through Kaplan-Meier curves and a Cox regression. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Results A total of 2,377 prisoners were included with a median follow-up time of 1,540.9 days per patient. Among the total population, 117 HCV seroconversions were detected (incidence of 1.17/100 py). The incidence was higher between 1992 and 1995 (2.57/100 py), among cases with HIV co-infection (8.34/100 py) and among intravenous drug users (IDU) without methadone treatment (MT) during follow-up (6.66/100 py). The incidence rate of HCV seroconversion among cases with a history of IDU and current MT was 1.35/100 py, which is close to that of the total study population. The following variables had a positive predictive value for HCV infection: IDU (p<0.001; HR = 7,30; CI: 4.83–11.04), Spanish ethnicity (p = 0.009; HR = 2,03; CI: 1.93–3.44) and HIV infection (p = 0.015; HR = 1.97; CI: 1.14–3.39). Conclusion The incidence of HCV infection among prisoners was higher during the first part of the study and among IDU during the entire study period. Preventative programs should be directed toward this sub-group of the prison population.

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts.

Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.

Directly observed therapy for chronic hepatitis C: A randomized clinical trial in the prison setting

BACKGROUND The diagnosis and treatment of chronic hepatitis C are major concerns in prisons. OBJECTIVES The aim of this randomized clinical trial was to determine the extent to which directly observed therapy (DOT) improved the efficacy of the standard treatment for chronic hepatitis C in the prison setting. PATIENTS AND METHODS A randomized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent standard treatment for chronic hepatitis C (based on pegylated interferon alpha-2a and ribavirin). RESULTS A total of 252 inmates were randomized, of which 244 were analyzed: 109 in the DOT group and 135 in the non-DOT group. The mean age was 35.88 years (SD 6.54), 94.3% were men, 72.1% reported intravenous drug use, 21.3% were HIV co-infected, and 55.3% had genotype 1 or 4. The patients received the study treatment for a median time of 33.9 weeks in the overall sample. Sustained virological response was achieved in 60.6% (95% CI, 51.17-69.22) of the DOT group and in 65.9% (95% CI, 57.59-73.38) of the standard therapy group (risk ratio=0.92; 95% CI, 0.76-1.12). The mean proportion of patients continuing the treatment was 83% (SD=31). Adverse events were reported in 93.4% of the patients, and serious adverse events were reported in 8.2%, with no significant differences between groups. CONCLUSIONS Sustained virological response was remarkably high, although there were no differences between groups, probably due to high treatment adherence.

Mortality, Causes of Death and Associated Factors Relate to a Large HIV Population-Based Cohort.

Introduction Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013. Materials and Methods We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models. Mortality Results 182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0–16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7–6.1/1000 py), external was lower [1.7/1000 py; (1.0–2.4/1000 py)]. Survival Results Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5–7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3–5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4–1.7) and heterosexual female (sHR:2.8; CI:1.1–7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7–123.2) and heterosexual male (sHR:11.8; CI:2.5–56.4) versus MSM. Conclusion and Recommendation There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males.

Personality disorders among Spanish prisoners starting hepatitis C treatment: Prevalence and associated factors

The purpose of this study was to assess the prevalence of personality disorders (PDs) and their associated factors in prisoners who initiate chronic hepatitis C (CHC) treatment in 25 Spanish prisons. The Personality Diagnostic Questionnaire-4 was used to diagnose PDs according to DSM-IV criteria. Factors potentially associated with a PD diagnosis were evaluated by logistic regression analysis. Two hundred and fifty-five patients were initially assessed and 62 (24.3%) were excluded due to an incomplete or invalid self-report screening questionnaire. PD prevalence was 70.5%, with antisocial PD being the most prevalent (46.1%). In terms of PD clusters, the most prevalent was cluster-B (55.4%). PD diagnosis was associated with HCV genotypes 1, 2, or 3 (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.02-4.49). Patients with a cluster-B PD were more likely to be infected with HCV genotypes 1, 2, or 3 (OR 2.37, 95% CI 1.08-5.23) and be HIV-infected (OR 2.20, 95% CI 1.10-4.39), to report past-year injection drug use (OR 7.17, 95% CI 1.49-34.58), and to have stage 3 or 4 fibrosis (OR 2.16, 95% CI 1.06-4.49). The prevalence of PDs in Spanish prisoners who initiate CHC treatment is very high. PD management issues should be considered in treating CHC patients in prisons.

Causas de no inicios al tratamiento de la hepatitis C en el medio penitenciario: subanálisis del estudio EPIBAND

Objetivo: Dentro del marco del estudio EPIBAND este subanalisis ha sido disenado para determinar las causas de no inicio del tratamiento para la hepatitis C cronica (HCC) en poblacion penitenciaria. Metodo: Estudio epidemiologico, prospectivo y multicentrico realizado en 26 centros. Se presentan los resultados del analisis correspondiente al grupo de pacientes incluidos en el estudio EPIBAND que por diferentes motivos no iniciaron el tratamiento antiviral. Resultados: Se analizaron un total de 195 pacientes (edad media de 39±6,6 anos, 86,7% varones, y 96,9% de nacionalidad espanola). Las principales razones de no inicio fueron aquellas secundarias al paciente en un 41% de los casos, razones medicas en un 30,8% y razones secundarias al medio en un 3,6%. El 47,5% de los pacientes refirio falta de motivacion y concienciacion, y en el 18,8% influyo el temor a sufrir efectos secundarios. Entre las razones medicas, la inmunodepresion constituyo la principal causa de contraindicacion en un 35% de los casos seguida de las alteraciones psiquiatricas y neurologicas en un 28,3%. La proxima excarcelacion o traslado a otro centro resultaron las principales variables asociadas al ambito penitenciario en un 64,6% de los pacientes. Conclusiones: La falta de motivacion y concienciacion del paciente, y el temor a sufrir efectos secundarios constituyen las principales causas de la negativa al tratamiento. Aspectos subjetivos y modificables que van a depender de la educacion y formacion del paciente asi como de la atencion prestada por los profesionales sanitarios en el curso del tratamiento. Palabras clave: estudio comparativo; VIH; pacientes; hepatitis C; tratamiento; prisiones; prisioneros; Espana.

Treatment of latent Mycobacterium tuberculosis infection in intravenous drug users co-infected with HIV

Objective: This clinical trial, carried out among injection drug users and the HIV-infected with tuberculin skin test ≥ 5 mm, aimed to evaluate the compliance and tolerability of two preventive strategies against tuberculosis (TB). Methods: Study protocol prospectively compares adherence to nine months of daily therapy with isoniazid (9H) versus two months of daily therapy with rifampin plus pyrazinamide (2RZ) administered randomly. All patients were concurrently admitted to a methadone maintenance programme. To assess toxicity, liver function was monitored monthly. Results: From 305 assessable patients, those in 2RZ arm showed better adherence (84% vs. 59%, p < 0.0001). Results on liver toxicity did not show significant differences between 9H and 2RZ (4.5% vs. 6.9%; odds ratio = 1.58, 95% confidence interval = 0.42—7.24). Conclusion: 2RZ should be considered an option to prevent TB in selected groups of patients infected with HIV, such as injection drug users on methadone treatment.

Validation of four AIDS-case definitions in HIV-infected intravenous drug users in Barcelona, Spain

The objective of the study is to assess the sensitivity and specificity of four epidemiological AIDS-Case Definitions (CDC-87, CDC-93, Europe-93 and Revised Caracas) in HIV-infected intravenous drug users (IDU). The authors carried out a cross-sectional study with 136 IDUs, HIV-infected from a Men Penitentiary Center and from a drug addiction treatment center of Barcelona, Spain, between October/93 and April/94. A protocol, including demographic, clinical and laboratory variables was used by one doctor and the laboratory tests were done in the same institution. After that, the patients were classified in the four Epidemiological AIDS-Case Definitions used by this study. As gold standard we used the CD4 Cell Count (out point 200 or 14% CD4+). The number of AIDS cases varied between 31 and 84 according to the type of AIDS definition. The CDC-93 AIDS definition implied an increase of 170.9% in the number of cases in relation to CDC-87 AIDS-Case Definition. The sensitivities of the CDC-87, CDC-93, Europe-93 and Revised Caracas Epidemiological AIDS - Case Definitions were 34.2, 88.6, 45.6 and 56.9% while the specificities were 93.0, 75.4, 75.4 and 77.2%, respectively. The positive predictive values were between 72.0% (Europe-93) and 87.1% (CDC-87) and the negative predictive values were between 50.0% (Europe-93) and 82.7% (CDC-93). The authors concluded: the sensitivity and specificity of Caracas Revised Epidemiological AIDS-Case Definition was better than Europe-93 AIDS Case Definition. So this Definition can be very useful in countries and situations where the CD4 Cell Count is not available for technical or economical reasons.