Interpreting the reasons for the choice and changing of two drug regimens in an observational cohort: comparison of a ritonavir-boosted protease inhibitor-based versus a nonnucleoside reverse transcriptase inhibitor-based first-line regimen.

OBJECTIVES: We compared reasons for the choice of regimen, time to and reasons for third drug modification, virological response and change in CD4 T-cell counts in patients started on atazanavir/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line regimens. METHODS: We included patients from the Cohort of the Spanish HIV Research Network (CoRIS), a multicentre cohort of HIV-positive treatment-naïve subjects, in the study. We used logistic regression to assess factors associated with choosing ATV/r vs. EFV, proportional hazards models on the subdistribution hazard to estimate subdistribution hazard ratios (sHRs) for third drug modification, logistic regression to estimate odds ratios (ORs) for virological response and linear regression to assess mean differences in CD4 T-cell count increase from baseline. RESULTS: Of 2167 patients, 10.7% started on ATV/r. ATV/r was more likely than EFV to be prescribed in injecting drug users [adjusted OR 1.85; 95% confidence interval (CI) 1.03-3.33], in 2009-2010 (adjusted OR 1.63; 95% CI 1.08-2.47) and combined with abacavir plus lamivudine (adjusted OR 1.53; 95% CI 0.98-2.43). Multivariate analyses showed no differences, comparing ATV/r vs. EFV, in the risk of third drug modification (sHR 1.04; 95% CI 0.74-1.46) or in virological response (OR 0.81; 95% CI 0.46-1.41); differences in mean CD4 T-cell count increase from baseline were at the limit of statistical significance (mean difference 29.8 cells/µL; 95% CI -4.1 to 63.6 cells/µL). In patients changing from EFV, 48% of changes were attributable to toxicity/adverse events, 16% to treatment failure/resistance, 3% to simplification, and 8 and 12%, respectively, to patients' and physicians' decisions; these percentages were 24, 6, 12, 14 and 24%, respectively, in those changing from ATV/r. CONCLUSIONS: ATV/r- and EFV-based regimens meet the requirements of both efficacy and safety for initial combination antiretroviral regimen, which relate to better durability.

Documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH / Consensus document on the management of renal disease in HIV-infected patients

OBJETIVO: Actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). MÉTODOS: Este documento ha sido consensuado por un panel de expertos del Grupo de Estudio de Sida (GESIDA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), de la Sociedad Española de Nefrología (S.E.N.) y de la Sociedad Española de Química Clínica y Patología Molecular (SEQC). Para la valoración de la calidad de la evidencia y la graduación de las recomendaciones se ha utilizado el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: La evaluación renal debe incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación chronic kidney disease epidemiological collaboration [CKD-EPI]), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. En este documento se revisan las indicaciones de derivación del paciente a Nefrología y las de la biopsia renal, así como las indicaciones y la evaluación y el manejo del paciente en diálisis o del trasplante renal. CONCLUSIONES: La función renal debe monitorizarse en todos los pacientes con infección por el VIH y este documento pretende optimizar la evaluación y el manejo de la afectación renal.(AU)

OBJECTIVE: To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. METHODS: This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. CONCLUSIONS: Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.(AU)

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.

The relationship between antiretroviral prescription patterns and treatment guidelines in treatment-naïve HIV-1-infected patients.

BACKGROUND: Reports have shown that the publication of practice guidelines does not guarantee their use in clinical practice. The objective of this study was to evaluate the agreement between antiretroviral treatments (ARTs) prescribed in clinical practice and the recommendations in published guidelines. METHODS: A retrospective cohort study was carried out in ART-naïve adults of the Spanish Asociacion Medica Vach de Estudios Multicentricos (VACH) Cohort for the period from 2003 to 2006. RESULTS: A total of 945 patients initiated ART. Of these patients, 12.3% had a CD4 cell count above 350 cells/microL. A 'nonrecommended' antiretroviral regimen was prescribed to 5.3, 5.1 and 7.8% of patients with CD4 counts <200, 200-350 and >350 cells/microL, respectively. Multivariate analyses demonstrated that only a higher viral load was associated with the selection of a combination treatment that was recommended by the guidelines. CONCLUSIONS: Most patients were prescribed initial treatments in agreement with the recommendations. Appropriate routine data collection in databases can be used to evaluate the level of antiretroviral guideline compliance. We propose that routine evaluations of the guidelines must be part of quality assessment to improve medical care.

Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

OBJECTIVES: The two currently available types of pegylated interferon (peg-IFN) used to treat hepatitis C have different pharmacokinetic properties. It is unclear how these differences affect response to therapy. We compared the effectiveness and safety of peg-IFN-alpha2a and peg-IFN-alpha2b, both with ribavirin, against chronic hepatitis C virus (HCV) infection in HIV-infected patients. METHODS: From the GESIDA HIV/HCV cohort, we analysed patients treated with peg-IFN-alpha2a (n = 315) or peg-IFN-alpha2b (n = 242). The primary endpoint was a sustained virological response (SVR). RESULTS: Both groups were well matched in baseline characteristics except for a higher frequency of injection drug users in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (85% versus 76%; P = 0.01) and a higher frequency of bridging fibrosis and cirrhosis (F3-F4) in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (42% versus 33%; P = 0.04). End-of-treatment response was significantly lower among patients treated with peg-IFN-alpha2b [40% versus 52%; odds ratio (OR), 1.63; 95% confidence interval (95% CI), 1.16-2.29; P < 0.01]. However, no significant differences were found in SVR between patients treated with peg-IFN-alpha2b and those treated with peg-IFN-alpha2a (31% versus 33%; OR, 1.09; 95% CI, 0.75-1.59; P = 0.655). Therapy was interrupted due to adverse events in 33 (14%) patients treated with peg-IFN-alpha2b and 47 (15%) patients treated with peg-IFN-alpha2a. CONCLUSIONS: No differences in effectiveness and safety were found between peg-IFN-alpha2b and peg-IFN-alpha2a for the treatment of chronic HCV infection in HIV-infected patients.

Incidence and risk factors for tuberculosis in HIV-positive subjects by HAART status.

OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.

Group A streptococcal bacteremia: outcome and prognostic factors / Bacteriemia por estreptococos del grupo A: resultados y factores pronóstico

In the last two decades, an increase in the incidence of invasive group A streptococcus (GAS) infections has been reported. The aim of this study was to determine the clinical and epidemiological characteristics and the natural history of GAS bacteremias at our hospital by performing a retrospective study of all cases of GAS bacteremia diagnosed at our University hospital from 1994 to 2003. We reported 42 cases of GAS bacteremia (27 men, mean age 42.3 ± 31.6 years). None had more than one episode and four cases were nosocomial. The mean annual incidence rate was 1.01 cases per 100,000 population. An increase in the incidence but not in severity of GAS bacteremia was observed in the last 5-year period (p<0.001). The rates were highest in young children and the elderly and those with underlying medical conditions; 73.8% of patients had some underlying chronic illness, and the most relevant conditions included peripheral vascular disease and diabetes mellitus. Mortality was high and the worst outcome corresponded to elderly patients with streptococcal toxic shock syndrome (STSS). Thirty patients (71.4%) had a disruption in the integrity of the skin barrier, 14 (33.3%) were immunocompromised patients and 6 patients (14.3%) were intravenous drug users. A source of the bacteremia was noted in 38 patients (90.5%), with skin and soft tissue infection being the major portals of entry. Twelve patients (28.6%) fulfilled the STSS criteria. All strains were susceptible to penicillin and vancomycin. Resistance to erythromycin was 21.4% and to ciprofloxacin was 17.5%. The global mortality rate was 28.6%. Only STSS was significantly associated with increased mortality in the multivariate analysis

En las dos últimas décadas se ha descrito un aumento de la incidencia de infecciones por estreptococos del grupo A invasivos. El objetivo de este estudio fue determinar las características clínicas y epidemiológicas y la historia natural de las bacteriemias por estreptococos del grupo A en nuestro hospital. Se estudiaron retrospectivamente todos los casos diagnosticados en un solo hospital de nivel terciario entre 1994 y 2003, y describimos 42 (27 varones, edad media 42,3 ± 31,6 años). Ninguno presentó más de un episodio y cuatro fueron infecciones nosocomiales. La tasa media de incidencia anual fue de 1,01 casos por 100.000 habitantes. Se ha observado un aumento en la incidencia de bacteriemia por estreptococos del grupo A, pero no de su gravedad, durante los últimos 5 años (p <0.001). Las tasas de incidencia más altas se observaron en niños y ancianos. El 73,8% de los pacientes afectados presentaron una enfermedad crónica subyacente, siendo las más relevantes la enfermedad vascular periférica y la diabetes mellitus. Treinta pacientes (71,4%) presentaban una herida u otra alteración de la integridad de la barrera cutánea, 14 (33%) estaban inmunodeprimidos y 6 (14,3%) eran drogadictos por vía intravenosa. En 38 casos (90,5%) se registró un foco de entrada de la bacteriemia, siendo los más habituales las infecciones cutáneas y de tejidos blandos. Doce pacientes (28,6%) cumplieron los criterios de síndrome de “shock” tóxico estreptocócico. Todas las cepas fueron sensibles a la penicilina y la vancomicina. La resistencia a la eritromicina fue del 21,4% y al ciprofloxacino del 17,5%. La tasa global de mortalidad fue del 28,6%. En el análisis multivariado, sólo el “shock” tóxico estreptocócico se asoció significativamente a una mayor mortalidad. Durante los últimos cinco años se ha observado un aumento en la incidencia de bacteriemia por estreptococos del grupo A en nuestro hospital. Los niños pequeños, los ancianos y los pacientes con enfermedades subyacentes son más susceptibles a adquirir esta infección. La mortalidad fue alta y los peores resultados se observaron en los pacientes ancianos con síndrome de “shock” tóxico estreptocócico

Group A streptococcal bacteremia: outcome and prognostic factors.

In the last two decades, an increase in the incidence of invasive group A streptococcus (GAS) infections has been reported. The aim of this study was to determine the clinical and epidemiological characteristics and the natural history of GAS bacteremias at our hospital by performing a retrospective study of all cases of GAS bacteremia diagnosed at our University hospital from 1994 to 2003. We reported 42 cases of GAS bacteremia (27 men, mean age 42.3 +/- 31.6 years). None had more than one episode and four cases were nosocomial. The mean annual incidence rate was 1.01 cases per 100,000 population. An increase in the incidence but not in severity of GAS bacteremia was observed in the last 5-year period (p<0.001). The rates were highest in young children and the elderly and those with underlying medical conditions; 73.8% of patients had some underlying chronic illness, and the most relevant conditions included peripheral vascular disease and diabetes mellitus. Mortality was high and the worst outcome corresponded to elderly patients with streptococcal toxic shock syndrome (STSS). Thirty patients (71.4%) had a disruption in the integrity of the skin barrier, 14 (33.3%) were immunocompromised patients and 6 patients (14.3%) were intravenous drug users. A source of the bacteremia was noted in 38 patients (90.5%), with skin and soft tissue infection being the major portals of entry. Twelve patients (28.6%) fulfilled the STSS criteria. All strains were susceptible to penicillin and vancomycin. Resistance to erythromycin was 21.4% and to ciprofloxacin was 17.5%. The global mortality rate was 28.6%. Only STSS was significantly associated with increased mortality in the multivariate analysis.

[Non-Hodgkin lymphomas with systemic presentation in patients with HIV infection. Clinical and prognostic factors in a series evaluated before the introduction of the highly active antiretroviral therapy (HAART)]. / Linfomas no hodgkinianos de presentación sistémica e infección por VIH. Análisis clínico y de factores pronóstico en una serie tratada antes de la introducción del tratamiento antirretrovírico de gran actividad.

PATIENTS AND METHOD: We studied patients with acquired human immunodeficiency virus (HIV) infection that developed non-Hodgkin's lymphoma (NHL) from January 1985 to October 2001. RESULTS: 44 patients (36 men, 8 women; median age 34 years) were included. Burkitt's lymphoma was diagnosed in 34%, and diffuse large cell B lymphoma in 29.5%. A history of AIDS diagnosis was detected in 20 cases (45%). International prognostic index (IPI) was 0-1 in 19 patients (43%), 2 in 12 (27%) and higher than 3 in 13 (30%). Chemotherapy was used in 64% of the patients, radiation therapy in 2% and both in 11%. Criteria for partial response were reached in 13 patients (29%), for complete remission in 2 (4%) and for stabilization in 1 (2%). Nine (20%) patients are alive (5 without disease), 22 (50%) died because of NHL, 5 (11%) died because of treatment associated toxicity and 8 died because of other causes. Median survival were 3 months, with a 1-year survival estimate of 24% and a 2-year survival estimate of 14%. In the univariate analysis of prognostic factors, IPI = 0-1 in comparison with IPI = 2-5 (p = 0.000), physical status (PS) < or = 2 (p = 0.021) and absence of B symptoms (p = 0.012) were significant. In the multivariate analysis, IPI = 0-1 was also significant (p = 0.000). CONCLUSIONS: Patients with HIV and NHL has multiple factors of poor prognosis. The survival is limited and chemotherapy toxicity is high. Patients with low IPI are a subgroup with better prognosis.

Abscesos hepáticos recidivantes por Klebsiella pneumoniae / Relapsing liver abscesses by Klebsiella pneumoniae

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[Environmental mycobacterial diseases in patients with and without HIV infection: epidemiology and clinical course]. / Enfermedades por micobacterias ambientales en pacientes con y sin infección por el VIH: características epidemiológicas, clínicas y curso evolutivo.

The objective of the present study was to ascertain the clinical features, risk factors, microbiologic spectrum and course of disease after treatment of infections by environmental mycobacteria (EM) in patients with and without HIV infection in our community. Eighty-eight patients with diseases caused by EM diagnosed between 1989 and 1997 were studied; 46 (52.7%) were HIV-positive. Mycobacterium kansasii was the most prevalent pathogen (54%) overall, followed by M. avium complex (40%). However, M. avium complex was most prevalent among HIV-positive patients (61%) and M. kansasii was most prevalent among HIV-negative patients (76%). Localized lung infections were most common among HIV-negative patients, whereas 74% of HIV-positive patients had disseminated disease. Among HIV-negative patients, chronic obstructive pulmonary disease and corticosteroid use were common associations. Pulmonary disease was subacute and non-specific in both patient groups, whereas abdominal pain was the first symptom of most patients with disseminated disease. On the chest films of 76% of the HIV-negative patients, we observed cavitation and infiltrates; 60% of HIV-negative patients had normal x-rays. No differences in antibiotic sensitivity were observed between strains from HIV-positive and HIV-negative patients. The prognosis was good in the HIV-negative group with combined therapy with 2 to 4 first-line antituberculous drugs, whereas response was poor in HIV-positive patients in spite of prolonged treatment with 3 to 5 drugs. Nevertheless, thanks to the highly effective anti-retroviral treatment of recent years, we seem to be observing improved response to therapy with less aggressive forms of EM disease.

Enfermedades por micobacterias ambientales en pacientes con y sin infección por el VIH: características epidemiológicas, clínicas y curso evolutivo / Environmental mycobacterial diseases in patients with and without HIV infection: epidemiology, clinical features and evolution

El objetivo del presente estudio ha sido averiguar las caraterísticas clínicas, los factores predisponentes, el espectro microbiológico y la evolución tras el tratamiento de las enfermedades por micobacterias ambientales (MA) en los pacientes con y sin infección por el virus de la inmunodeficiencia humana (VIH) de nuestra población. Se han revisado 88 pacientes diagnosticados de enfermedades por MA entre 19891997; 46 de ellos (52,7 por ciento) eran VIH positivos. Globalmente, Mycobacterium kansasii ha sido la MA con mayor prevalencia (54 por ciento), seguida de Mycobacterium complex (40 por ciento). Sin embargo, en los pacientes VIH positivos predominó M. avium complex (61 por ciento) y en los VIH negativos M. kansasii (76 por ciento). Las formas de enfermedad en los VIH negativos fueron pulmonares y localizadas, mientras que el 74 por ciento de los VIH positivos presentaron formas diseminadas. Entre los pacientes seronegativos era frecuente padecer una enfermedad pulmonar obstructiva crónica o consumir corticoides. El cuadro clínico fue subagudo e inespecífico en las formas pulmonares de ambos grupos de pacientes, mientras que la mayor parte de individuos con formas diseminadas comenzaron con molestias abdominales. En el 76 por ciento de los casos VIH negativos se encontraron infiltrados cavitados en la radiografía de tórax y el 60 por ciento de VIH positivos presentó la radiografía normal. Las pruebas de sensibilidad antimicrobiana no evidenciaron diferencias entre las cepas que afectaron a VIH positivos y negativos. El pronóstico fue muy bueno en el grupo VIH negativo utilizando combinaciones de 2 a 4 antituberculosos de primera línea, mientras que entre los VIH positivos la respuesta fue pobre pese al empleo de tratamientos prolongados con 3 a 5 fármacos. No obstante, en los últimos años del estudio, debido al tratamiento antirretroviral altamente efectivo, parece observarse una mejor respuesta terapéutica con formas menos agresivas de enfermedad por MA. (AU)

Progression to acquired immunodeficiency syndrome in 94 human immunodeficiency virus-positive hemophiliacs with long-term follow-up.

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV) infection was transmitted to many hemophilics treated with non-inactivated factor concentrates before 1986. The aim of this study was to know the long-term incidence of AIDS and risk factors for its development in HIV-infected hemophiliacs. DESIGN AND METHODS: This study was a retrospective analysis of 94 HIV-infected hemophilics. The cumulative incidence of AIDS during a follow-up of 16 years from seroconversion was determined by Kaplan-Meier analysis,and potential risk factors were also studied by multivariate analysis. RESULTS: The 16-year estimated incidence of AIDS was 38% (95%CI 27%-52%). The AIDS incidence was significantly higher in patients with hemophilia B (p <0.0001), older age at seroconversion (p=0.0004), lower CD4 counts at seroconversion (p=0.004), and lower concentrate consumption during follow-up (p=0.02), than it was in those patients without these characteristics. However, only hemophilia type and age at seroconversion remained significant in the multivariate analysis, with a relative risk of 0.06 (95%CI 0.02-0.20) for hemophilia A and 1.04(95%CI 1.01-1.06) for every year of increase in age at seroconversion. The severity of hemophilia, history of inhibitors and concentrate consumption before seroconversion were not significantly associated with AIDS development. INTERPRETATION AND CONCLUSIONS: A considerable proportion of HIV-infected hemophiliacs remained AIDS-free 16 years after seroconversion. The risk of AIDS was particularly high in patients with hemophilia B and for patients who were older at seroconversion.

Fiebre con exantema y meningismo: una forma de presentación de la infección aguda por el virus de la inmunodeficiencia humana / fever, exanthema and meningism: a form of presentation of acute human

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