Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Impact of universal access to hepatitis C therapy on HIV-infected patients: implementation of the Spanish national hepatitis C strategy.

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Dimension of chronic hepatitis C virus in HIV-infected patients in the interferon-free era: an overview from south Spain.

The implementation of hepatitis C (HCV) direct-acting antiviral drugs is prioritized in several populations in which its application provides the most immediate and impactful benefit. In this scenario, a precise knowledge of the situation of human immunodeficiency virus (HIV)/HCV chronic co-infection is required to adequately address this disease. This cross-sectional study was performed in 21 hospitals in Andalusia (Spain). The study population consisted of HIV-infected patients with an active HCV chronic infection who were not receiving HCV treatment at the time of inclusion. A total of 13,506 HIV-infected patients were included in the study. Of them, 2561 (18.9 %) presented chronic HCV infection. The majority of the patients included were on highly active antiretroviral therapy (HAART; 96.2 %), showed plasma levels with an undetectable HIV viral load (92.5 %), and had a good immunological status (median CD4+ cell count of 486 cells/mL). The HCV genotype distribution was as follows: 58.1 % were genotype 1, 1.1 % were genotype 2, 16.1 % were genotype 3, and 22.1 % were genotype 4 (2.6 % were missing data). In total, 24.8 % of the patients showed liver fibrosis stage F0-F1, 27.9 % showed stage F2, 16.7 % showed stage F3, and 21 % showed stage F4 (9.6 % were missing data). With regards to previous HCV treatment experiences, 68.05 % of the patients were naïve and 31.95 % had failed to respond to a previous treatment. The burden of HCV/HIV co-infected patients in our population was reported as one in five HIV-infected patients requiring HCV treatment. The implementation of extra resources to face this important health challenge is mandatory.

Concomitant tuberculosis and lung cancer diagnosed by bronchoscopy.

SETTING: South Granada Health Area (SGHA), Spain. OBJECTIVE: To describe the characteristics of concomitant tuberculosis (TB) and lung cancer cases. DESIGN: A total of 319 TB cases diagnosed between January 2003 and December 2010 were evaluated and identified using a prospective database. During this period, samples of bronchial secretions were obtained from all patients who underwent fibreoptic bronchoscopy (FBS) as part of a TB screening programme. A descriptive study was conducted. RESULTS: Concomitant TB and lung cancer were diagnosed in 15 cases (4.7% of total TB cases). The most common radiographic finding was atelectasis (53.3%), and the most common histological type was epidermoid carcinoma (60%). Lung cancer stage was advanced (III-IV) in 60% of the cases. CONCLUSION: The association between TB and lung cancer found in the SGHA after implementing a TB screening programme was higher than in other studies. This suggests that it would be advisable to perform acid-fast bacilli smear and mycobacterial culture of bronchial aspirates in all patients with presumed lung cancer, particularly in high TB prevalence areas.

Rational application of adenosine deaminase activity in cerebrospinal fluid for the diagnosis of tuberculous meningitis.

PURPOSE: Tuberculous meningitis (TBM) is one of the most serious and difficult to diagnose manifestations of TB. An ADA value >9.5 IU/L has great sensitivity and specificity. However, all available studies have been conducted in areas of high endemicity, so we sought to determine the accuracy of ADA in a low endemicity area. METHODS: This retrospective study included 190 patients (105 men) who had ADA tested in CSF for some reason. Patients were classified as probable/certain TBM or non-TBM based on clinical and Thwaite's criteria. Optimal ADA cutoff was established by ROC curves and a predictive algorithm based on ADA and other CSF biochemical parameters was generated. RESULTS: Eleven patients were classified as probable/certain TBM. In a low endemicity area, the best ADA cutoff was 11.5 IU/L with 91 % sensitivity and 77.7 % specificity. We also developed a predictive algorithm based on the combination of ADA (>11.5 IU/L), glucose (<65 mg/dL) and leukocytes (≥13.5 cell/mm(3)) with increased accuracy (Se: 91 % Sp: 88 %). CONCLUSIONS: Optimal ADA cutoff value in areas of low TB endemicity is higher than previously reported. Our algorithm is more accurate than ADA activity alone with better sensitivity and specificity than previously reported algorithms.

Bone mineral density and bone turnover in non-cirrhotic patients with chronic hepatitis C and sustained virological response to antiviral therapy with peginterferon-alfa and ribavirin.

UNLABELLED: Patients with chronic hepatitis C have low bone mineral density and increased bone resorption related to serum transaminase levels. Elevated serum soluble tumor necrosis factor (sTNFR-55) receptor levels may play a role in the bone mass loss in these patients. Bone mass is improved and bone turnover normalized in patients who respond to antiviral therapy with interferon and ribavirin. INTRODUCTION: Low bone mineral density (BMD) has been described in patients with chronic hepatitis C (HCV). The study objective was to evaluate the effect of antiviral therapy on BMD and bone metabolism in non-cirrhotic HCV patients with sustained virological response. METHODS: We conducted a prospective study in 36 consecutive outpatients from the general community with non-cirrhotic HCV and an early and sustained virological response to peginterferon-alfa and ribavirin therapy. Determinations of BMD (dual X-ray absorptiometry at lumbar spine and femoral neck) and biochemical measurements of bone metabolism and sTNFR-55 were made at baseline, after 24 and 48 weeks of antiviral therapy, and at 48 weeks after the end of treatment. RESULTS: Patients had a significantly reduced BMD, which significantly increased during the follow-up. Serum levels of sTNFR-55 and bone turnover markers were increased at baseline and significantly reduced at all subsequent time points. We found an inverse correlation between BMD and both serum aminotransferase levels and urine deoxypyridinoline (D-pyr) and a positive correlation between serum aminotransferases and both urine D-Pyr and serum sTNFR-55. CONCLUSIONS: Patients with chronic hepatitis C have low bone mass associated with increased bone resorption, and some relationship can be expected between serum aminotransferase levels and the degree of bone mass loss. Bone mass may be improved and bone turnover normalized in patients who respond to antiviral therapy. Elevated serum sTRFR-55 levels may play a role in the bone mass loss of these patients.

Safety analysis of high dose (>6 mg/kg/day) daptomycin in patients with concomitant statin therapy.

There is a paucity of data regarding efficacy and safety of concomitant therapy of daptomycin and statins, so we reviewed patients that concomitantly received daptomycin and statins to identify any potential increase in toxicity in our cohort. This retrospective study included all patients that received >6 mg/kg/day of daptomycin along with statins and had efficacy and safety data. Patients on high dose (>6 mg/kg/day) daptomycin therapy that did not received statins served as controls. One hundred four patients were included. Median daptomycin dose was 7.8 mg/kg/day (range 6.5-10.8 mg/kg/day), for a mean duration of therapy of 17 days (range 10-51 days). Thirty-six patients received daptomycin and statins and 68 received only daptomycin. Muscular toxicity defined as CPK levels>1000 UI/L (2.5 times upper normal limit, range of determination 200-400 UI/L) was equally distributed between both groups (3/36, 8% vs 7/68, 10%; p=0.746). Despite biochemical toxicity, we did not find clinical toxicity and daptomycin treatment was completed in all cases. We did not find predictors of increased CPK during daptomycin therapy. Based on our data, concomitant administration of daptomycin and statins is safe and is not associated with an increased risk of rhabdomyolysis.

[The Strategic Plan for the development of Internal Medicine in Andalusia]. / El Plan Estratégico para el desarrollo de la Medicina Interna en Andalucía.

The Strategic Plan for the Development of Internal Medicine in Andalusia arose from the need that the internal medicine doctors had to redefine the purpose and values of their specialty to cope with the numerous changes occurring in the health care area. The project was developed in three phases. First, the tendency of the health care system and current position of the specialty were analyzed. After, the internal and external opinions on the present-future of Internal Medicine were checked out. Finally, five strategic lines with their action plans were established. Specific objectives were defined within each line: results to be achieved, methodology according to action plan. After several years of collegial work in this initiative, very positive results have been achieved. We conclude that the Strategic Plan has been useful to better define the position of our specialty and to state which tools such as those mentioned are effective to cope with the new challenges that may occur in other groups.

Clinical spectrum of fever of intermediate duration in the south of Spain.

Fever of intermediate duration (FID) is a new nosologic entity defined as fever higher than 38 degrees C that has a duration of between 1 and 4 weeks and that after an initial approach has not been diagnosed. It has clinical similarities with fever of unknown origin, but because of characteristic etiologies it requires the term FID. We describe the clinical characteristics and etiology of FID in the south of Spain and create a treatment algorithm. Retrospective study of the medical charts of patients attending at our Service during 2000 and 2005 who had an initial diagnosis of FID and who had a complete follow-up until the resolution of symptoms. Two hundred and thirty-three patients met the inclusion criteria, of whom 164 were men. Median number of days before being referred to our service was 9 (range 2-28). Half of the patients had elevation of transaminases, and CRP and ESR were slightly elevated, 2.8 mg/dl (range 0.1-50) and 16 mm/h (range 1-131) respectively. A final diagnosis was made in 80 patients, with infection with coxiella (32 patients), CMV (16 patients), rickettsial species (11 patients), VEB virus (6 patients), and brucella (5 patients) being the more frequent entities. Doxycycline was the antibiotic most frequently prescribed. Among patients with Q fever, CMV, and rickettsial infection, the majority had abnormal hepatic function, (87%, 93%, and 55% respectively). In FID, a diagnosis is reached in a minority of patients, although the prognosis is excellent in most of them. In our patients the clinical picture of Q fever, CMV, and rickettsial infections included abnormal hepatic function. In addition, these three infections are the most frequently diagnosed so when treating a patient with FID, if elevation of liver enzymes is present patients should start on doxycycline.

El Plan Estratégico para el desarrollo de la Medicina Interna en Andalucía / The strategic plan for the development of internal medicine in Andalusia

El Plan Estratégico para el Desarrollo de la MedicinaInterna en Andalucía surgió de la necesidad sentidapor los internistas de redefinir la misión y valores denuestra especialidad, para afrontar los numerososcambios que estaban ocurriendo en la arenasanitaria. El proyecto se desarrolló en tres fases:primero se analizaron las tendencias del sistemasanitario y la situación actual de la especialidad;posteriormente se pulsó la opinión interna y externasobre el presente-futuro de la Medicina Interna; yfinalmente se establecieron 5 líneas estratégicas consus planes de acción. Dentro de cada línea sedelimitaron objetivos específicos, resultados alograr, y metodología acorde al plan de acción. Trasvarios años de trabajo colegiado en esta iniciativa sehan logrado resultados muy positivos. Concluimosque el Plan Estratégico ha resultado útil para situarmejor nuestra especialidad, y que herramientascomo la detallada son efectivas para afrontar nuevosretos que puedan acaecer a otros colectivos

The Strategic Plan for the Development of InternalMedicine in Andalusia arose from the need thatthe internal medicine doctors had to redefine thepurpose and values of their specialty to cope withthe numerous changes occurring in the health carearea. The project was developed in three phases.First, the tendency of the health care system andcurrent position of the specialty were analyzed.After, the internal and external opinions on thepresent-future of Internal Medicine were checkedout. Finally, five strategic lines with their actionplans were established. Specific objectives weredefined within each line: results to be achieved,methodology according to action plan. After severalyears of collegial work in this initiative, very positiveresults have been achieved. We conclude that theStrategic Plan has been useful to better definethe position of our specialty and to state which toolssuch as those mentioned are effective to cope withthe new challenges that may occur in other groups (AU)

[Use of anamnesis and immunological techniques in the diagnosis of anisakidosis in patients with acute abdomen]. / Utilidad de la anamnesis y de las técnicas inmunológicas en el diagnóstico de la anisakidosis en pacientes con abdomen agudo.

INTRODUCTION: Anisakis simplex can be a cause of digestive symptoms. Our aim was to evaluate the epidemiological antecedents and immunological data available for a differentiation between patients with anisakidosis and those with other acute abdominal problems. PATIENTS AND METHODS: this is a prospective cohort study involving 134 patients with acute abdominal problems: 52 patients were diagnosed with anisakidosis by means of surgical and pathological findings and/or specific IgE seroconversion against Anisakis simplex (group A), and in 82 patients anisakidosis had been ruled out (group NA: non-anisakidosis). We evaluated the antecedent of raw fish ingestion, the skin prick test, and IgE immunoblotting as diagnostic tools. RESULTS: patients in groups A and NA differ in terms of prior raw fish ingestion (p < 0.0001) and positive SPT (p < 0.0001), with their respective negative predictive values (NPV) being 98.39% (95%CI: 90.17-99.92) and 95.56% (95%CI: 83.64-99.23). Regarding immunoblotting, in 86.2% of patients in group A a band of 60 kDa was detected, which was also detected in 19.2% of patients in group NA. CONCLUSIONS: a negative answer to the question about raw or undercooked fish ingestion has very high sensitivity and NPV (98.39%), and is thus reasonably reliable to rule out anisakidosis. The absence of cutaneous sensitization to crude A. simplex extract gives a high probability (95.56%) that the illness is absent. The presence of a band of about 60 kDa in immunoblotting would be useful for diagnosis.

Utilidad de la anamnesis y de las técnicas inmunológicas en el diagnóstico de la anisakidosis en pacientes con abdomen agudo / No disponible

Introducción: Anisakis simplex puede producir síntomas digestivosy alérgicos. En este trabajo se evalúan los antecedentesepidemiológicos y los resultados inmunológicos para diferenciarentre pacientes con anisakidosis y aquellos con otras patologíasdigestivas que cursan con dolor abdominal.Pacientes y método: estudio de cohortes realizado con 134pacientes: 52 fueron diagnosticados de anisakidosis por los hallazgosquirúrgicos y anatomopatológicos y/o seroconversión específicafrente a A. simplex (grupo A) y en 82 pacientes la anisakidosisfue excluida como diagnóstico (grupo NA: no-anisakidosis). Sehan evaluado el antecedente de ingesta de pescado crudo, laprueba cutánea en prick (PC) y el inmunoblot IgE como elementosde diagnóstico.Resultados: los pacientes de los grupos A y NA mostraron resultadosdiferentes respecto a la de ingesta de pescado crudo (p <0,0001) y la PC (p < 0,0001), con valores predictivos negativos(VPN) del 98,39 y 95,56% y positivos (VPP) del 70,83 y 87,50%,respectivamente. En el inmunoblot, se halló una banda de aproximadamente60 kDa en el 86,2 y 19,2% de los pacientes del grupoA y NA, respectivamente (VPP: 62,50%; VPN: 94,03%).Conclusiones: en pacientes con dolor abdominal, la ingesta depescado crudo o poco cocinado tiene elevada sensibilidad y VPN(98,39%) pero menor VPP (70,83%), por lo que nos ayuda principalmentea descartar la anisakidosis. La ausencia de sensibilizacióncutánea al extracto crudo de A. simplex apoya la ausencia de anisakidosiscon una probabilidad alta (95,56%). La presencia de una bandade 60 kDa en el inmunoblot podría ser útil para su diagnóstico

Introduction: Anisakis simplex can be a cause of digestivesymptoms. Our aim was to evaluate the epidemiological antecedentsand immunological data available for a differentiationbetween patients with anisakidosis and those with other acute abdominalproblems.Patients and methods: this is a prospective cohort study involving134 patients with acute abdominal problems: 52 patientswere diagnosed with anisakidosis by means of surgical and pathologicalfindings and/or specific IgE seroconversion againstAnisakis simplex (group A), and in 82 patients anisakidosis hadbeen ruled out (group NA: non-anisakidosis). We evaluated theantecedent of raw fish ingestion, the skin prick test, and IgE immunoblottingas diagnostic tools.Results: patients in groups A and NA differ in terms of priorraw fish ingestion (p < 0.0001) and positive SPT (p < 0.0001),with their respective negative predictive values (NPV) being98.39% (95%CI: 90.17-99.92) and 95.56% (95%CI: 83.64-99.23). Regarding immunoblotting, in 86.2% of patients in groupA a band of 60 kDa was detected, which was also detected in19.2% of patients in group NA.Conclusions: a negative answer to the question about raw orundercooked fish ingestion has very high sensitivity and NPV(98.39%), and is thus reasonably reliable to rule out anisakidosis.The absence of cutaneous sensitization to crude A. simplex extractgives a high probability (95.56%) that the illness is absent.The presence of a band of about 60 kDa in immunoblotting would be useful for diagnosis (AU)

Septic arthritis due to Absidia corymbifera in a patient with HIV-1 infection.

We report the first case described of septic arthritis caused by Absidia corymbifera in the setting of cellular immune deficiency associated with HIV-1 infection. Isolation of this organism from sterile fluids as synovial fluid should be regarded as pathogenic.

Tratamiento de la hepatitis crónica por VHC / Chronic hepatitis C treatment

La infección por VHC (virus de la hepatitis C) constituye un problema sanitario de gran magnitud, que afecta aproximadamente al 2% de la población mundial, aunque existen diferencias de prevalencia en función del área geográfica, que es del 1-2% en Europa Occidental y llega al 10% en países como Egipto y algunos otros de Asia

HCV (hepatitis C virus) infection is a major health problem, affecting approximately 2% of the world’s population, although there are differences in prevalence in terms of geographical area, with 1-2% in Western Europe and as much as 10% in countries such as Egypt and others in Asia

Retrospective analysis of antiretroviral HIV treatment success based on medical history or guided by the reverse hybridisation LiPA HIV genotyping system.

The changes in viral load and CD4(+) count at 3 and 6 months in a group of 166 HIV-infected patients was evaluated. The new therapy was chosen based on the medical history procedures for 70 patients, and in 96 patients it was guided by the partial or complete result of the line probe assay (LiPA) HIV RT and Protease resistance tests. The absolute difference from the baseline of the log viral load at 3 and 6 months was significantly different between the two groups when adjusted for baseline viral load (P < 0.0001) and stayed significant when intention-to-treat analysis was carried out (P < 0.001). The absolute difference of the CD4(+) count was not significantly different when adjusted for baseline CD4(+) (P = 0.854, 3 months; P = 0.06, 6 months). The proportion of patients with a viral load