Asunción Hernando

The natural history of liver cirrhosis in HIV-hepatitis C virus-coinfected patients.

Objective:To provide detailed information about the natural history of HIV–hepatitis C virus (HCV)-coinfected patients with cirrhosis. Methods:Prospective cohort including 340 HIV–HCV-coinfected patients with compensated (n = 248) or decompensated (n = 92) cirrhosis. We evaluated predictors of survival and of first hepatic decompensation. Results:The mortality rate for patients with decompensated and compensated cirrhosis was 27.14 deaths per 100 person-years [95% confidence interval (CI) 18.93–35.35] and 3.98 deaths per 100 person-years (95% CI 2.42–5.54), respectively. Rate of first hepatic decompensation in patients with compensated cirrhosis was 4.62 per 100 persons-years (95% CI 2.91–6.33). In the complete cohort, permanent HAART interruption during follow-up, CD4 cell count nadir and baseline Child-Pugh score (CPS) B or C were significantly associated with shorter survival. In patients with compensated cirrhosis factors significantly associated with decreased survival were having the first hepatic decompensation during follow-up, permanent HAART discontinuation, and CPS B and C at baseline. For patients with compensated cirrhosis, time since diagnosis of HCV infection, CPS B and C and permanent HAART discontinuation were significantly associated with the risk of first hepatic decompensation. Sustained viral response to anti-HCV therapy was not independently associated with better survival in patients with compensated cirrhosis. Conclusion:HIV–HCV-coinfected patients with cirrhosis have a relatively good 3-year survival (87%). In contrast, 2-year survival of patients with decompensated liver cirrhosis is only 50%. Three-year survival was mostly impacted by liver-related factors and HAART maintenance.

Neurocognitive Impairment in Patients Treated with Protease Inhibitor Monotherapy or Triple Drug Antiretroviral Therapy

Background In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment. Methods In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed. Results Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15). Conclusions Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

A Prospective Cohort Study of Neurocognitive Function in Aviremic HIV-Infected Patients Treated With 1 or 3 Antiretrovirals

BACKGROUND The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. METHODS We prospectively included aviremic (≥1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for ≥1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. RESULTS Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. CONCLUSIONS The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia.

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain

While hepatitis C virus (HCV) infection seems to be expanding among HIV‐infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV‐infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1–27.5) in 2004–2005 to 8.2% (95% CI, 6.9–9.5) in 2010–2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0–8.9%; and heterosexual women, 14.5–4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4–76.4), birth decade 1961–1970 (OR, 2.1; 95% CI, 1.1–3.7) and low educational level (OR, 2.4; 95% CI, 1.6–3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.

Overall and cause-specific excess mortality in HIV-positive persons compared with the general population: Role of HCV coinfection

AbstractWe aimed to estimate overall and cause-specific excess mortality of HIV-positive patients compared with the general population, and to assess the effect of risk factors.We included patients aged >19 years, recruited from January 1, 2004 to May 31, 2014 in Cohort of the Spanish Network on HIV/AIDS Research. We used generalized linear models with Poisson error structure to model excess mortality rates.In 10,340 patients, 368 deaths occurred. Excess mortality was 0.82 deaths per 100 person-years for all-cause mortality, 0.11 for liver, 0.08 for non-AIDS-defining malignancies (NADMs), 0.08 for non-AIDS infections, and 0.02 for cardiovascular-related causes. Lower CD4 count and higher HIV viral load, lower education, being male, and over 50 years were predictors of overall excess mortality. Short-term (first year follow-up) overall excess hazard ratio (eHR) for subjects with AIDS at entry was 3.71 (95% confidence interval [CI] 2.66, 5.19) and 1.37 (95% CI 0.87, 2.15) for hepatitis C virus (HCV)-coinfected; medium/long-term eHR for AIDS at entry was 0.90 (95% CI 0.58, 1.39) and 3.83 (95% CI 2.37, 6.19) for HCV coinfection. Liver excess mortality was associated with low CD4 counts and HCV coinfection. Patients aged ≥50 years and HCV-coinfected showed higher NADM excess mortality, and HCV-coinfected patients showed increased non-AIDS infections excess mortality.Overall, liver, NADM, non-AIDS infections, and cardiovascular excesses of mortality associated with being HIV-positive were found, and HCV coinfection and immunodeficiency played significant roles. Differential short and medium/long-term effects of AIDS at entry and HCV coinfection were found for overall excess mortality.

Tratamiento antirretroviral de gran actividad administrado una vez al día: ¿presente o futuro?

La posibilidad de administrar el tratamiento antirretroviral en una unica toma diaria (QD) se ha contemplado como un objetivo deseable durante mucho tiempo. Diversas encuestas confirman la idea de que los pacientes prefieren un tratamiento administrado una vez al dia, al menos si el numero total de pastillas es bajo. La experiencia en el tratamiento de otras enfermedades cronicas indica que este tipo de regimenes podria mejorar las tasas de adherencia (un aspecto critico para la duracion de la respuesta antiviral). En la actualidad ya es posible disenar combinaciones potentes de antirretrovirales en las que todos los farmacos se dosifican una vez al dia, y el numero de estas combinaciones crece rapidamente. Sin embargo, son muchas las dudas y las incertidumbres que asaltan al clinico cuando se plantea utilizar este tipo de pautas, con las que su experiencia es, logicamente, menor. En todo caso, la utilizacion de pautas QD de tratamiento antirretroviral no debe hacernos olvidar que la potencia de los regimenes esta determinada por los farmacos que la componen, y que no todos los farmacos presentan una farmacocinetica que permita su dosificacion en una unica toma al dia con posibilidad de tolerar las variaciones en el horario de tomas que la vida real impone. La eleccion de regimenes QD tendra, por tanto, que individualizarse y situarse en el contexto personal y terapeutico del paciente; es responsabilidad del medico conocer las ventajas y limitaciones de cada una de las pautas posibles.

Influencia del hospital de día en los requerimientos de ingreso hospitalario de los pacientes con sida

Fundamento El hospital de dia se ha generalizado como estructura asistencial para pacientescon sida, pero no se ha evaluado su influencia sobre los requerimientos de ingreso hospitalariode estos pacientes. Metodos Estudio observacional y longitudinal de una cohorte de 308 pacientes diagnosticadosde sida entre 1990 y 1994 y seguidos hasta junio de 1996 en dos hospitales universitarios. Seanalizan los requerimientos de ingreso hospitalario en funcion de la disponibilidad de hospitalde dia en el centro donde se realiza su seguimiento. Para el analisis multivariante del numerode ingresos se utilizo una regresion ajustada a una distribucion de Poisson. Resultados Tras el diagnostico de sida se registraron 108 ingresos por 100 pacientes y ano deseguimiento, que supusieron 21 dias de ingreso por paciente y ano. Tras ajustar por el recuentode linfocitos CD4+ y el tipo de enfermedad diagnostica de sida presentada, los pacientesque dispusieron de hospital de dia ingresaban menos (riesgo relativo: 0,64; intervalo de confianzadel 95%: 0,55-0,76), lo que supuso entre 11 y 31 dias menos de ingreso por paciente alo largo de su seguimiento. No hubo diferencias en la supervivencia de los pacientes en funciondel hospital en el que eran controlados. Conclusiones La existencia de un hospital de dia disminuye los requerimientos de ingreso hospitalariode pacientes con sida, fundamentalmente en los pacientes con mayor depresion inmunologica.

The impact of participatory teaching methods on medical students’ perception of their abilities and knowledge of epidemiology and statistics

Statistics and Epidemiology are crucial both in clinical decision-making and clinical research. Teaching these disciplines in a Bachelor’s Degree in Medicine is a significant challenge. In this paper, we aim to describe two participatory teaching methods used in a yearlong second-year course that includes both Epidemiology and Statistics, and to analyze how these two methodologies affect the students’ perception of the course and their abilities related to these subjects. Both methodologies consist in carrying out a specific practical activity. The first practical activity is carried out using a website and aims to help students understand concepts and interpret information; the second involves analyzing a database using a statistical package and, subsequently, producing a scientific report. In addition, we prepared a questionnaire to find out the students’ perception of these issues. The nine questionnaire items were assessed using a rating scale and adapted to characteristics of the course, which covers Epidemiology and Statistics in an integrated manner. Then we assessed the differences in perception before and after the activities were carried out. The results show that the students’ perception improved significantly in the following items: “importance of Statistics and Epidemiology in Medicine”; “usefulness in clinical practice”; “understanding concepts”; “ability to perform a statistical analysis”; and “ability to sort data”. The difference was not significant in the remaining four items. In conclusion, the students’ perception of their ability in Statistics and Epidemiology significantly improved after completing the practical activities, and their perception of importance and usefulness of these subjects also improved.

Toward a comprehensive care of HIV patients: Finding a strategy to detect depression in a Spanish HIV cohort

ABSTRACT Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.

Interpretación y consideraciones metodológicas y estadísticas en los estudios de rescate

The methodology used in studies of rescue therapy is sometimes complex. This is because of the heterogeneity of objectives and options. Firstly, the definition of failure has multiple interpretations and subtle distinctions. Secondly, the aim of treatment in these patients has varied according to the available treatment options in each case and at each moment of time. Lastly, the methodology used to develop these studies of rescue therapy has varied over time in line with changes in their aims and options. Currently, a new change can be expected to adjust to the current situation, since the number of therapeutic options for rescue therapy has substantially increased in the last year. The present review discusses changes in the design of these studies, the main methodological issues to be taken into account and the recommendations on this subject.