Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. OBJECTIVES: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. METHODS: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. RESULTS: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. CONCLUSIONS: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.

Necrotizing Sarcoid Granulomatosis: A Disease Not to be Forgotten.

Sarcoidosis is a systemic granulomatous disease of unknown aetiology characterised by the appearance of noncaseifying epithelioid granulomas in the affected organs, most commonly the lungs, skin, and eyes (Iannuzzi et al. 2007). Necrotizing Sarcoid Granulomatosis (NGS) is a rare and little-known form of disease, which also presents nodular lung lesions, and it shares pathologic and clinical findings with sarcoidosis, where the presence of necrosis may lead to misdiagnosis of tuberculosis (TB), leading to a consequent delay in treatment of the underlying entity (Chong et al. 2015). This is exactly what happened with the two cases that we present here.

Parenteral drug use as the main barrier to hepatitis C treatment uptake in HIV-infected patients.

OBJECTIVES: Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV-coinfected patients. METHODS: A prospective longitudinal study was carried out. HIV-infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct-acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow-up and those who were not. RESULTS: Of the 15 556 HIV-infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow-up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment-naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST-PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST-PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409-0.746) and recent PWID (OR 0.019; 95% CI 0.004-0.087) were identified as independent factors associated with low odds of treatment implementation. CONCLUSIONS: We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

Uveítis anterior en paciente con infección aguda por citomegalovirus ¿casualidad o causalidad? / Anterior uveitis in a patient with acute cytomegalovirus infection: Casualty or causality?

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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.

Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort.

The aim was to analyze clinical complications in HIV-infected subjects who persistently maintain low CD4 levels despite virological response to cART in the Spanish CoRIS cohort. The main inclusion criteria were CD4 counts <200cells/mm(3) at cART-initiation and at least 2years under cART achieving a viral load <500copies/mL. Those patients with CD4 counts <250cells/mm(3) 2years after cART were classified as the Low-CD4 group, and clinical events were collected from this time-point. Poisson regression models were used to calculate incidence rate ratios of death, AIDS-defining events, serious non-AIDS-defining events (NAE) and of each specific NAE category (non-AIDS-defining malignancies (non-ADM), cardiovascular, kidney- and liver-related events). Of 9667 patients in the cohort, a total of 1128 met the criteria and 287 (25.4%) were classified in the Low-CD4 group. A higher risk of death (aIRR: 4.71; 95% CI: 1.88-11.82; p-value=0.001) and of non-ADM were observed in this group (aIRR: 2.23; 95% CI: 1.07-4.63; p=0.03). Our results stress the need to control accelerated aging in this population to counter their increased risk of non-AIDS-defining diseases, particularly cancer, and are consistent with the concept that clinical complications are potentially affected by genetics and lifestyle.

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.

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

Ecografía de partes blandas

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Dermatitis en paciente con leucemia mieloide crónica / Dermatitis in a patient with chronic myeloid leukemia

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