Bilateral Adrenalectomy in a Patient With Refractory Primary Aldosteronism Due to Adrenal Hyperplasia.

Primary aldosteronism (PA) is a frequent cause of secondary hypertension. The main cause of PA is bilateral adrenal hyperplasia, and treatment is usually medical with mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone. In this paper, we present a rare clinical case of a middle-aged female with refractory arterial hypertension and hypokalemia that complementary medical tests confirmed PA due to bilateral hyperplasia, and despite a maximum dose of spironolactone and oral potassium supplements, there was no clinical response. Because of this, finally, the patient needed surgical treatment based on bilateral adrenalectomy, which was effective. This is unusual and poorly described in the medical literature.

The Role of TPOAb in Thyroid-Associated Orbitopathy: A Systematic Review.

INTRODUCTION: Thyroid-associated orbitopathy (TAO) is one of the most common autoimmune inflammatory disorders of the orbit. The presence of anti-thyroid antibodies is believed to play a role in the pathogenesis and clinical status of the TAO patients. Herein, we review the usefulness of TPOAb as a biomarker for TAO. METHODS: A systematic search in MEDLINE library was conducted. Results: Twenty studies were included. TPO is expressed in orbital tissues, and the polymorphism rs11675434 SNP has proven to be associated with clinically evident TAO. Studies in pediatric patients have shown a positive correlation between high TPOAb levels and TAO. In contrast, results in adults are inconsistent. Some studies imply a protective role of TPOAb, yet the majority did not find any association. Some authors have suggested an implication of TPOAb in the pathophysiology of TAO in TRAb-negative patients. CONCLUSIONS: The role of TPOAb in TAO remains unclear and controversial.

[Evaluation of tools for the implementation of clinical practice guidelines on sexually transmitted infections]. / Evaluación de herramientas de implementación de la Guía de Práctica Clínica de infecciones de transmisión sexual.

OBJECTIVE: Determine the acceptability, perceived usefulness, and adoption of implementation tools and technical assistance provided by the Health Technology Assessment Institute (IETS) in hospitals in two regions of Colombia. METHODS: Assistance was provided for implementation of clinical practice guidelines (CPGs) in 24 hospitals (17 in Antioquia and seven in Cundinamarca) in areas with high prevalence of sexually transmitted infections, and for use of the implementation tools. Health professionals were given surveys and medical specialists were interviewed. RESULTS: Overall, 86% of respondents are familiar with the GPGs, 86% with the tracer recommendations, 79% with the interactive flow charts, and 82% with the evidence sheets, while 41% never used the implementation tools. Of the respondents who used the tools, 55% did so on their work computer, while 24% used their personal telephone. The most useful tools were the evidence sheets and flow charts (98%) and the tracer recommendations (92%). The least useful were the budgetary impact tools (81%). CONCLUSIONS: The implementation tools and technical assistance provided in hospitals in two regions of Colombia are perceived as useful and acceptable, although the degree of implementation is low. The findings of this research will help the different actors, such as the Ministry of Health and Social Protection, the IETS, and the Administrative Department of Science, Technology and Innovation (Colciencias), among others, improve their programs for the implementation of clinical practice guidelines.

Evaluación de herramientas de implementación de la Guía de Práctica Clínica de infecciones de transmisión sexual / Evaluation of tools for the implementation of clinical practice guidelines on sexually transmitted infections

Objetivo. Establecer la aceptabilidad, percepción de utilidad y la implantación de las herramientas de implementación y el acompañamiento técnico del Instituto de Evaluación Tecnológica en Salud (IETS) en los hospitales de dos regiones de Colombia. Métodos. Se desarrolló acompañamiento para la implementación de la Guía de Práctica Clínica (GPC) en 24 hospitales (17 de Antioquía y 7 de Cundinamarca) en zonas de alta prevalencia de infecciones de transmisión sexual (ITS), así como la instalación de las herramientas de implementación. Se aplicaron encuestas a los profesionales y entrevistas a los referentes. Resultados. Del total de los encuestados, 86% conocen la GPC, 86% las recomendaciones trazadoras, 79% los flujogramas interactivos, 82% las hojas de evidencia y 41% nunca utilizó las herramientas de implementación. De los encuestados que han utilizado las herramientas, 55% lo hacen en el ordenador del sitio de trabajo, mientras que 24% utiliza su teléfono personal. Las herramientas de mayor utilidad son las hojas de evidencia y los flujogramas con 98% y las recomendaciones trazadoras con 92%. Las de más baja utilidad son las herramientas de impacto presupuestal (81%). Conclusiones. Las herramientas de implementación y el acompañamiento técnico en los hospitales de dos regiones de Colombia se perciben como útiles y aceptables, aunque el grado de implantación es bajo. Los hallazgos de esta investigación contribuirán para que los diferentes actores, como el Ministerio de Salud y Protección Social, el IETS y el Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) entre otros, puedan mejorar los programas de implementación de guías de práctica clínica.

Objective. Determine the acceptability, perceived usefulness, and adoption of implementation tools and technical assistance provided by the Health Technology Assessment Institute (IETS) in hospitals in two regions of Colombia. Methods. Assistance was provided for implementation of clinical practice guidelines (CPGs) in 24 hospitals (17 in Antioquia and seven in Cundinamarca) in areas with high prevalence of sexually transmitted infections, and for use of the implementation tools. Health professionals were given surveys and medical specialists were interviewed. Results. Overall, 86% of respondents are familiar with the GPGs, 86% with the tracer recommendations, 79% with the interactive flow charts, and 82% with the evidence sheets, while 41% never used the implementation tools. Of the respondents who used the tools, 55% did so on their work computer, while 24% used their personal telephone. The most useful tools were the evidence sheets and flow charts (98%) and the tracer recommendations (92%). The least useful were the budgetary impact tools (81%). Conclusions. The implementation tools and technical assistance provided in hospitals in two regions of Colombia are perceived as useful and acceptable, although the degree of implementation is low. The findings of this research will help the different actors, such as the Ministry of Health and Social Protection, the IETS, and the Administrative Department of Science, Technology and Innovation (Colciencias), among others, improve their programs for the implementation of clinical practice guidelines.

Evaluación de herramientas de implementación de la Guía de Práctica Clínica de infecciones de transmisión sexual / Evaluation of tools for the implementation of clinical practice guidelines on sexually transmitted infections

RESUMEN Objetivo Establecer la aceptabilidad, percepción de utilidad y la implantación de las herramientas de implementación y el acompañamiento técnico del Instituto de Evaluación Tecnológica en Salud (IETS) en los hospitales de dos regiones de Colombia. Métodos Se desarrolló acompañamiento para la implementación de la Guía de Práctica Clínica (GPC) en 24 hospitales (17 de Antioquía y 7 de Cundinamarca) en zonas de alta prevalencia de infecciones de transmisión sexual (ITS), así como la instalación de las herramientas de implementación. Se aplicaron encuestas a los profesionales y entrevistas a los referentes. Resultados Del total de los encuestados, 86% conocen la GPC, 86% las recomendaciones trazadoras, 79% los flujogramas interactivos, 82% las hojas de evidencia y 41% nunca utilizó las herramientas de implementación. De los encuestados que han utilizado las herramientas, 55% lo hacen en el ordenador del sitio de trabajo, mientras que 24% utiliza su teléfono personal. Las herramientas de mayor utilidad son las hojas de evidencia y los flujogramas con 98% y las recomendaciones trazadoras con 92%. Las de más baja utilidad son las herramientas de impacto presupuestal (81%). Conclusiones Las herramientas de implementación y el acompañamiento técnico en los hospitales de dos regiones de Colombia se perciben como útiles y aceptables, aunque el grado de implantación es bajo. Los hallazgos de esta investigación contribuirán para que los diferentes actores, como el Ministerio de Salud y Protección Social, el IETS y el Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias) entre otros, puedan mejorar los programas de implementación de guías de práctica clínica.

ABSTRACT Objective Determine the acceptability, perceived usefulness, and adoption of implementation tools and technical assistance provided by the Health Technology Assessment Institute (IETS) in hospitals in two regions of Colombia. Methods Assistance was provided for implementation of clinical practice guidelines (CPGs) in 24 hospitals (17 in Antioquia and seven in Cundinamarca) in areas with high prevalence of sexually transmitted infections, and for use of the implementation tools. Health professionals were given surveys and medical specialists were interviewed. Results Overall, 86% of respondents are familiar with the GPGs, 86% with the tracer recommendations, 79% with the interactive flow charts, and 82% with the evidence sheets, while 41% never used the implementation tools. Of the respondents who used the tools, 55% did so on their work computer, while 24% used their personal telephone. The most useful tools were the evidence sheets and flow charts (98%) and the tracer recommendations (92%). The least useful were the budgetary impact tools (81%). Conclusions The implementation tools and technical assistance provided in hospitals in two regions of Colombia are perceived as useful and acceptable, although the degree of implementation is low. The findings of this research will help the different actors, such as the Ministry of Health and Social Protection, the IETS, and the Administrative Department of Science, Technology and Innovation (Colciencias), among others, improve their programs for the implementation of clinical practice guidelines.

Monotherapy with darunavir/ritonavir is effective and safe in clinical practice.

INTRODUCTION: Monotherapy against HIV has undoubted theoretical advantages and has good scientific fundaments. However, it is still controversial and here we will analyze the efficacy and safety of MT with darunavir with ritonavir (DRV/r) on patients who have received this treatment in our hospitals. MATERIALS AND METHODS: Observational retrospective study that includes patients from 10 Andalusian hospitals that have received DRV/r in MT and that have been followed over a minimum of 12 months. We carried out a statistical descriptive analysis based on the profile of patients who had been prescribed MT and the efficacy and safety that were observed, paying special attention to treatment failure and virological evolution. RESULTS: DRV/r was prescribed to 604 patients, of which 41.1% had a CD4 nadir <200/mmc. 33.1% had chronic hepatitis caused by HCV, had received an average of five lines of previous treatment and had a history of treatment failure to analogues in 33%, to non-analogues 22 and protease inhibitors (PI) in 19.5%. 76.6% proceeded from a previous treatment with PI. The simplification was the main criteria for the instauration of MT in the 81.5% and the adverse effects in the 18.5%. We managed to maintain MT in 84% of cases, with only 4.8% of virological failure (VF) with viral load (VL) >200 c/mL and 3.6% additional losses due to VF with VL between 50 and 200 copies/mL. Thirty three genotypes were performed after failure without findings of resistance mutations to DRV/r or other IPs. Only 23.7% of patients presented some blips during the period of exposition to MT. Eighty seven percent of all determinations of VL had <50 copies/mL, and only 4.99% had >200 copies/mL. Although up to 14.9% registered at some point an AE, only 2.6% abandoned MT because of AE and 1.2% because of voluntary decision. Although the average of total and LDL cholesterol increases 10 mg/dL after 2 years of follow-up, so did HDL cholesterol in 3mg/dL and the values of triglycerides (-14 mg/dL) and GPT (-6 UI/mL) decreased. The average count of CD4 lymphocytes increased from 642 to 714/mm(3) at 24 weeks. CONCLUSIONS: In a very broad series of patients obtained from clinical practice, data from clinical trials was confirmed: MT with DRV as a de-escalation strategy is very safe, it's associated to a negligible rate of adverse effects and maintains a good suppression of HIV replication. VF (with >50 or >200 copies/mL) is always under 10% and in any case without consequences.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS: Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.

Dyslipidaemia in HIV-infected women on antiretroviral therapy. Analysis of 922 patients from the Spanish VACH cohort.

BACKGROUND: Information concerning lipid disturbances in HIV-infected women on antiretroviral therapy (ART) is scarce. The objective of the study is to describe the lipid profile in a large cohort of HIV-infected women on contemporary ART and analyse differences between regimes and patient's characteristics. METHODS: Observational, multicentre, cross-sectional study from the Spanish VACH Cohort. 922 women on stable ART without lipid-lowering treatment were included. RESULTS: Median age was 42 years, median CD4 lymphocyte count was 544 cells/mm3, and 85.6% presented undetectable HIV-1 viral load. Median total cholesterol (TC) was 189 mg/dL (interquartile range, IQR, 165-221), HDL cholesterol 53 mg/dL (IQR, 44-64), LDL cholesterol 108 mg/dL (IQR, 86-134), and triglycerides 116 mg/dL (IQR, 85-163). Mean accumulated time on ART was 116 months; 47.4% were on NNRTI-based regimes, 44.7% on PI, and 6.7% on only-NRTI therapy. 43.8% were also hepatitis C (HCV) coinfected. Patients on PI treatment presented higher TC/HDL ratio than those on NNRTI (p < 0.001). Significantly higher HDL values were observed in NNRTI-treated patients. HCV-coinfected patients presented lower TC/HDL ratio than the non HCV-coinfected. In multivariate analysis, factors independently associated with TC/HDL ratio were age, triglyceride levels and HCV co-infection. PI treatment presented a non-significant association with higher TC/HDL ratio. CONCLUSIONS: In HIV-infected women, the NNRTI-based ART is associated with a better lipid profile than the PI-based. Factors unrelated to ART selection may also exert an independent, significant influence on lipids; in particular, age, and triglyceride levels are associated with an increased TC/HDL ratio while HCV co-infection is associated with a reduced TC/HDL ratio.

Bacterial translocation in HIV-infected patients with HCV cirrhosis: implication in hemodynamic alterations and mortality.

OBJECTIVE: Analysis of the influence of portal hypertension on intestinal permeability in HIV-infected patients with hepatitis C virus (HCV)-related cirrhosis and of the prognostic significance of consequent macrophage activation. METHODS: Twenty HIV-monoinfected patients, 70 patients with HIV-HCV coinfection, 20 of them with compensated and 50 with decompensated cirrhosis, and 20 healthy controls were evaluated for intestinal permeability [measured by lipopolysaccharide-binding protein (LBP) serum levels], macrophage activation [soluble CD14, soluble tumour necrosis factor receptor 55 Kd, and interleukin 6 (IL-6)], and activation of the rennin-angiotensin-aldosterone axis. Patients with decompensated cirrhosis were monitored for a median period of 429 days to analyze the prognostic factors implicated in survival. RESULTS: Patients with decompensated cirrhosis show increased LBP levels compared with HIV-monoinfected patients. Patients with increased LBP concentration showed elevated soluble CD14, soluble tumour necrosis factor receptor 55 Kd, and IL-6 levels. Twenty-two patients died, from liver-related causes, during the follow-up, and 2 more underwent liver transplantation. Child-Pugh index, CD4 T-cell count, plasma aldosterone and serum IL-6 concentrations independently predicted liver-related mortality. CONCLUSIONS: Increased intestinal permeability, as measured by serum LBP levels, observed in patients with HIV infection is significantly higher in patients with decompensated liver cirrhosis. Proinflammatory cytokines (IL-6) are prognostic markers of HIV-HCV-coinfected patients with decompensated cirrhosis.

Tuberculin skin-test reactions are unaffected by the severity of hyperendemic intestinal helminth infections and co-infections.

The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (> or = 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species.

Characteristics and outcome of HIV infection in gypsies in the Spanish VACH Cohort

Objective To study the characteristics of HIV infection in the gypsy (Roma) population in Spain, as compared with those of the Caucasian, non-gypsy majority. Design Cross-sectional, historical cohort study from the Spanish VACH Cohort. Methods Patients attending VACH clinics between 1 June 2004 and 30 November 2004 were classified according to their racial and ethnic origin as “gypsies”, Caucasian non-gypsy Spanish natives (CNGN), and “other” (the last being excluded from this study). Their sociodemographic and clinico-epidemiological characteristics were compared, as well as the Kaplan–Meier curves of time to AIDS, or death, or disease progression (either of the 2 outcomes).Results4819 (48%) of 10,032 cases included in the VACH database were eligible: 210 (4.2%) were gypsies and 4252 (84.8%) were CNGN. Differences were observed in age, household, academic, inmate, marital, and employment history. Injecting drug use had been the most frequent mechanism of transmission in both groups, but to a greater extent among gypsies (72% versus 50%; P<0.000). Sex distribution, CD4 cell counts, and viral loads at the first visit were similar in the 2 groups, as was the percentage of patients with previous AIDS, percentage receiving antiretrovirals, and percentage subsequently starting antiretroviral therapy. Up to 1 April 2005, 416 new AIDS cases and 85 deaths were recorded. The percentage of these outcomes did not differ between groups, but log-rank test showed a shorter time to AIDS and disease progression among gypsies. Conclusions The sociodemographic characteristics of gypsies, the largest minority in the VACH Cohort, show differences relative to those of CNGN. HIV-related outcomes suggest that gypsies have a poorer prognosis (AU)

Objetivo estudiar las características de la infección por el VIH en gitanos en España, en comparación con las de la mayoría caucásica no gitana (CNG).Métodos estudio transversal y de cohortes históricas en la Cohorte VACH. Clasificamos a los pacientes que acudieron a las clínicas participantes en VACH entre el 1 de junio de 2004 y el 30 de noviembre de 2004 de acuerdo a su raza y etnia, como «gitanos», «nativos españoles CNG» u «otros» (estos, excluidos de este estudio). Comparamos sus características sociodemográficas y clinicoepidemiológicas, así como sus curvas de Kaplan–Meier del tiempo hasta sida, muerte o progresión de la enfermedad (cualquiera de ambos).Resultados4819 (48%) de 10.032 casos recogidos en la base de datos de VACH fueron incluidos en el estudio: 210 (4,2%) eran gitanos y 4.252 (84,8%) eran nativos CNG. Observamos diferencias en sus distribuciones por edad, domicilio, estudios, antecedentes penales, situación laboral y marital. La inyección de drogas había sido el mecanismo de transmisión del VIH más frecuente en los dos grupos, pero más marcadamente en los gitanos (72% frente a 50%; p<0,000). La distribución por sexos, los recuentos de linfocitos CD4 y las cargas virales en la primera visita fueron similares en ambos grupos, así como las proporciones de pacientes con sida previo y las de quienes estaban ya en, o iniciaron entonces, tratamiento antirretroviral. Hasta el 1 de abril de 2005 se registraron 416 nuevos casos de sida y 85 muertes. La proporción de ambos resultados fue similar en ambos grupos, pero la prueba del rango logarítmico demostró una evolución más rápida a sida y a progresión de la (..) (AU)

Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study.

BACKGROUND: Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. METHODS: Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. RESULTS: Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV <50 copies/ml) was 67.7% (CI95: 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollment and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003). CONCLUSIONS: Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.

Characteristics and outcome of HIV infection in gypsies in the Spanish VACH Cohort.

OBJECTIVE: To study the characteristics of HIV infection in the gypsy (Roma) population in Spain, as compared with those of the Caucasian, non-gypsy majority. DESIGN: Cross-sectional, historical cohort study from the Spanish VACH Cohort. METHODS: Patients attending VACH clinics between 1 June 2004 and 30 November 2004 were classified according to their racial and ethnic origin as "gypsies", Caucasian non-gypsy Spanish natives (CNGN), and "other" (the last being excluded from this study). Their sociodemographic and clinico-epidemiological characteristics were compared, as well as the Kaplan-Meier curves of time to AIDS, or death, or disease progression (either of the 2 outcomes). RESULTS: 4819 (48%) of 10,032 cases included in the VACH database were eligible: 210 (4.2%) were gypsies and 4252 (84.8%) were CNGN. Differences were observed in age, household, academic, inmate, marital, and employment history. Injecting drug use had been the most frequent mechanism of transmission in both groups, but to a greater extent among gypsies (72% versus 50%; P<0.000). Sex distribution, CD4 cell counts, and viral loads at the first visit were similar in the 2 groups, as was the percentage of patients with previous AIDS, percentage receiving antiretrovirals, and percentage subsequently starting antiretroviral therapy. Up to 1 April 2005, 416 new AIDS cases and 85 deaths were recorded. The percentage of these outcomes did not differ between groups, but log-rank test showed a shorter time to AIDS and disease progression among gypsies. CONCLUSIONS: The sociodemographic characteristics of gypsies, the largest minority in the VACH Cohort, show differences relative to those of CNGN. HIV-related outcomes suggest that gypsies have a poorer prognosis.

Effectiveness and safety of didanosine, lamivudine and efavirenz versus zidovudine, lamivudine and efavirenz for the initial treatment of HIV-infected patients from the Spanish VACH cohort.

BACKGROUND: Preliminary data suggest that a once-daily combination of lamivudine, didanosine and efavirenz is an effective alternative regimen for antiretroviral-naive HIV-1-infected patients. However, data from randomized trials comparing this combination versus standard first-line regimens are not available yet. In an observational study, we analyse the efficacy and tolerability of didanosine plus lamivudine and efavirenz versus zidovudine plus lamivudine and efavirenz in a cohort of therapy naive patients. METHODS: We performed an observational study on prospectively collected data from patients participating in a multicentre Spanish treatment-naive cohort (VACH cohort). Efficacy was assessed comparing time to therapeutic failure and CD4 cell recovery. Safety was analysed comparing the proportion of patients who discontinued therapy for toxicity or any other reason. RESULTS: Overall, 219 patients treated with once-daily didanosine/lamivudine/efavirenz and 409 patients receiving twice-daily zidovudine/lamivudine (Combivir) plus efavirenz were evaluated. By intent-to treat analysis (non-completers and therapeutic change=failure), time to treatment failure was similar in both groups of treatment: 40.0 months (95% CI 23.3-56.8 months) among patients on didanosine/lamivudine/efavirenz and 33.3 months (95% CI 25.6-41.1 months) in patients treated with zidovudine/lamivudine/efavirenz (P=0.253). The risk of failure due to treatment change was almost double among patients treated with zidovudine/lamivudine/efavirenz compared with those who received didanosine/lamivudine/efavirenz. CONCLUSIONS: Our data suggest that didanosine/lamivudine/efavirenz is a combination with an efficacy comparable to zidovudine/lamivudine/efavirenz as first-line therapy for HIV infection. The risk of treatment change was significantly higher among patients treated with zidovudine/lamivudine/efavirenz than in those starting therapy with didanosine/lamivudine/efavirenz.

First-line antiretroviral therapy with efavirenz or lopinavir/ritonavir plus two nucleoside analogues: the SUSKA study, a non-randomized comparison from the VACH cohort.

BACKGROUND: Efavirenz and lopinavir/ritonavir are both recommended antiretroviral agents for combination first-line therapy, although information on direct comparisons between them is scarce. A retrospective longitudinal study from the VACH cohort comparing both regimens was performed. METHODS: Efficacy was examined comparing time to virological failure, CD4 recovery and clinical progression. Tolerability was examined comparing time to treatment discontinuation for any reason and for toxicity. Survival analysis was conducted using the Kaplan-Meier method, and standard and weighted Cox regression models. RESULTS: A total of 1550 antiretroviral-naive patients starting a two-nucleoside reverse transcriptase inhibitor regimen plus either efavirenz (n = 1159) or lopinavir/ritonavir (n = 391) were included in the study. At baseline, patients starting lopinavir/ritonavir had higher HIV-1 RNA and lower CD4+ cell counts. There was no difference in the adjusted hazards of virological failure [efavirenz versus lopinavir/ritonavir hazard ratio (HR) = 0.93, 95% confidence interval (CI): 0.77-1.12, P = 0.43], CD4 recovery (HR = 1.11, 95% CI: 0.95-1.30, P = 0.19) and clinical progression (HR = 0.71, 95% CI: 0.39-1.31, P = 0.27). There was an increased risk of discontinuation for any reason or for toxicity for lopinavir/ritonavir (HR = 2.10, 95% CI: 1.40-3.15, P = 0.0003). CD4 recovery with both drugs was also similar in the lowest CD4 strata. A higher risk of early hypertriglyceridaemia was associated with lopinavir/ritonavir-based regimens. CONCLUSIONS: Our study suggests similar virological efficacy for efavirenz- or lopinavir/ritonavir-based first-line antiretroviral regimens, but an increased risk of discontinuation because of toxicity in case of lopinavir/ritonavir-based therapy. Immunological outcome appeared similar with both regimens.

Natural history of compensated and decompensated HCV-related cirrhosis in HIV-infected patients: a prospective multicentre study.

OBJECTIVE: To define the course of HIV-HCV-coinfected patients with compensated and decompensated liver cirrhosis and to investigate the survival and the risk factors for death. PATIENTS AND METHODS: Ninety-two HIV-infected patients with HCV-related cirrhosis (50 of them without and 42 with previous decompensations) were prospectively followed up during a median period of 20 months. Clinical, biochemical, virological and immunological factors were analysed. Multivariate analyses were performed of those factors associated with decompensations and mortality. RESULTS: There were 168 readmissions due to liver-disease-related causes. A Child-Pugh index > or =6 in those without previous decompensations (hazard ratio [HR] 7.94, 95% confidence interval [CI] 1.59-39.58; P = 0.014), and Child-Pugh index > or =9 (HR 2.68, 95% CI 1.13-6.33; P = 0.003) and absence of HAART (HR 0.44, 95% CI 0.19-0.98; P = 0.048) in those with previous decompensations were independently associated with decompensation during the follow up. There were 27 deaths, 22 of them attributable to liver disease. Independent factors associated with liver-related mortality were a Child-Pugh index > or =9 (HR 6.24, 95% CI 2.31-16.85; P < 0.001), progression of Child-Pugh index during the follow up (HR 4.27, 95% CI 1.54-11.80; P = 0.008), more than one decompensation (HR 24.25, 95% CI 7.27-40.45; P < 0.001) and absence of HAART (HR 0.35, 95% CI 0.12-0.98; P = 0.002). CONCLUSIONS: Evolution from compensated to decompensated cirrhosis and death is influenced by markers of liver function and the absence of HAART. The importance of this last element must be adequately stressed.

[Changing trends in HIV epidemics: recent diagnoses in the Spanish VACH cohort (2000-2002)]. / Patrón epidemiológico de la infección por el VIH en 15 hospitales españoles: casos de nuevo diagnóstico incluidos en la cohorte VACH en 2001 y 2002.

BACKGROUND: Studying the changing trends of HIV epidemics is a useful means of evaluating the results of current preventive plans as well as of defining future needs and objectives. METHODS: We performed a cross-sectional study of the newly-diagnosed cases of HIV infection included in the Spanish VACH cohort. New HIV cases were defined as those diagnosed between January 2001 and December 2002. Their epidemiologic characteristics were compared with those of patients included in the same cohort who had been diagnosed between January 1998 and December 2000. RESULTS: We studied 603 new cases (27% women). In 146 (24.4%) HIV infection had been acquired by sharing material for intravenous drug use (IVDU), 171 (28,6%) were men who had had sex with other men (MSM) and 247 (41.3%) acknowledged some risk for heterosexual HIV transmission. The median age was 36 years (range: 18-80). Only 1.5% of the patients were younger than 20 years while 32.1% were older than 40 years. This percentage was significantly higher than that corresponding to 1998-2000 (27.5%; p < 0,05). HIV infection was diagnosed simultaneously with an AIDS-defining condition in 13.3% of patients and an AIDS-defining disease was diagnosed in the first month after HIV-diagnosis in another 40 patients (6.6%). CONCLUSIONS: We confirm the trends observed in previous studies: a growing proportion of newly diagnosed cases among women, a decreasing proportion of IVDU, a growth of MSM, and a trend toward diagnosis at a later age.

Patrón epidemiológico de la infección por el VIH en 15 hospitales españoles: casos de nuevo diagnóstico incluidos en la cohorte VACH en 2001 y 2002 / Changing trends in HIV epidemics: recent diagnoses in the Spanish VACH cohort (2000-2002)

ANTECEDENTES. El estudio de los cambios en las tendencias de la epidemia del virus de la inmunodeficiencia humana(VIH) constituye un método útil para evaluar los resultados de los planes preventivos actuales, así como para definir futuras necesidades y objetivos de los próximos. MÉTODOS. Estudio descriptivo transversal de los casos nuevos incluidos en la cohorte VACH. Definimos “caso nuevo” a los sujetos cuyo diagnóstico de infección por el VIH se realizó entre enero de 2001 y diciembre de 2002. Comparamos sus características epidemiológicas con las de los sujetos incluidos en la misma cohorte diagnosticados de infección por el VIH entre enero de 1998 y diciembre de 2000. RESULTADOS. Estudiamos 603 nuevos casos (27% mujeres).En 146 (24,4%) el riesgo de transmisión había sido el uso de drogas (usuarios de drogas por vía parenteral, UDVP),171 (28,6%) eran hombres que tuvieron relaciones sexuales con otros hombres (HSH) y 247 (41,3%) reconocían alguna exposición heterosexual de riesgo. La mediana de edad fue 36 años (límites: 16-80). Solamente 1,5% tenían menos de 20 años y 32,1% superaban 40 años. Este porcentaje fue significativamente superior al correspondiente al trienio 98-00 (27,5%; p < 0,05). La infección por VIH se diagnosticó simultáneamente con alguna complicación definitoria de sida en 13,3% casos y otros 40 pacientes (6,6%) la desarrollaron durante el primer mes tras el diagnóstico. CONCLUSIONES. Confirmamos las tendencias observadas en estudios previos: crecimiento de la proporción de mujeres con diagnóstico reciente de VIH, progresiva disminución de la proporción de UDVP y aumento de HSH y tendencia al diagnóstico en edades más avanzadas (AU)

BACKGROUND. Studying the changing trends of HIV epidemics is a useful means of evaluating the results of current preventive plans as well as of defining future needs and objectives. METHODS. We performed a cross-sectional study of the newly-diagnosed cases of HIV infection included in the Spanish VACH cohort. New HIV cases were defined as those diagnosed between January 2001 and December 2002. Their epidemiologic characteristics were compared with those of patients included in the same cohort who had been diagnosed between January 1998 and December 2000. RESULTS. We studied 603 new cases (27% women). In 146 (24.4%) HIV infection had been acquired by sharing material for intravenous drug use (IVDU), 171 (28,6%) were men who had had sex with other men (MSM) and 247 (41.3%) acknowledged some risk for heterosexual HIV transmission. The median age was 36 years (range: 18-80).Only 1.5% of the patients were younger than 20 years while 32.1% were older than 40 years. This percentage was significantly higher than that corresponding to 1998-2000 (27.5%; p < 0,05). HIV infection was diagnosed simultaneously with an AIDS-defining condition in 13.3% of patients and an AIDS-defining disease was diagnosed in the first month after HIV-diagnosis in another 40 patients (6.6%). CONCLUSIONS. We confirm the trends observed in previous studies: a growing proportion of newly diagnosed cases among women, a decreasing proportion of IVDU, a growth of MSM, and a trend toward diagnosis at a later age (AU)

[Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study]. / Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva.

INTRODUCTION: To assess the long-term effectiveness, safety and response-related factors in a cohort of HIV-infected persons receiving antiretroviral therapy containing nelfinavir. Design and setting. Prospective, non-randomized multicenter study. METHOD: A total of 792 patients were included: 254 (32.1%) treatment-naive patients and 538 (67.9%) patients previously treated with protease inhibitors who were switched to a nelfinavir-containing regimen due to virological failure or intolerance. Factors related to virological response and to treatment failure were assessed by standard survival techniques and Cox proportional risk models. RESULTS: Nelfinavir was well tolerated; treatment had to be interrupted in only 57 patients (7.1%) because of toxicity. During a median follow-up of 12 months, 31 patients (3.9%) experienced a new AIDS-defining event or death, and 463 (58.4%) showed immunological response. Overall, 52% patients achieved plasma HIV-1 RNA levels below 500 copies/mL (57% of naive and 49% of previously treated patients), but a high rate of virological rebound (24% and 49%, respectively) was observed. Low baseline viral load and few prior treatments were factors related to virological response. Naive treatment status and a high increase in CD4 cell count were predictive of longer viral response. CONCLUSIONS: Highly active antiretroviral therapy with a nelfinavir-containing regimen was associated with favorable virological response in nearly half of previously treated patients, and most experienced clinical and immunological benefits. Nevertheless, the limited duration of virological response indicates the need for new alternative drugs.

Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva / Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study

INTRODUCCIÓN. Evaluar la eficacia, tolerancia y factores asociados a la respuesta a largo plazo en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con un tratamiento que incluya nelfinavir. DISEÑO. Estudio prospectivo y multicéntrico, no aleatorizado. MÉTODO. Se incluyeron un total de 792 pacientes: 254 (32,1 por ciento) sin ningún tratamiento previo y 538 (67,9 por ciento) previamente tratados con inhibidores de la proteasa (IP) que cambiaron a un régimen con nelfinavir. El análisis se realizó mediante el método de curvas actuariales de Kaplan-Meier y modelos de riesgo proporcional de Cox. RESULTADOS. Nelfinavir fue bien tolerado y tan sólo 57 pacientes (7,1 por ciento) interrumpieron el tratamiento debido a efectos secundarios. Tras un año de seguimiento medio, 31 pacientes (3,9 por ciento) tuvieron un nuevo episodio definitorio de sida o muerte y se observó respuesta inmunológica en 463 (58,4 por ciento). Globalmente, el 52 por ciento de los pacientes alcanzó una carga viral indetectable (57 por ciento de vírgenes y 49 por ciento de pretratados), pero un alto porcentaje de ellos (24 y 49 por ciento, respectivamente) experimentó un rebrote tras una favorable respuesta inicial. Los factores relacionados con la respuesta virológica fueron una baja carga viral al inicio y un menor número de tratamientos previos. Los pacientes sin tratamiento previo y con una respuesta inmunológica mayor tuvieron una respuesta viral más duradera. CONCLUSIONES. El tratamiento antirretroviral con nelfinavir consigue una respuesta viral favorable en casi la mitad de los pacientes pretratados y la mayoría experimentan un beneficio clínico e inmunológico. Sin embargo, la limitada durabilidad de la respuesta virológica pone de manifiesto la necesidad de nuevos fármacos alternativos (AU)