Factors associated with the number of drugs in darunavir/cobicistat regimens.

BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Incidence of lymphoma in HIV-HCV-infected patients. Modifications in function of the anti-hepatitis C virus therapy.

The change in the incidence of lymphomas in function of the presence or absence of sustained virological response after anti-hepatitis C therapy in a cohort of human immunodeficiency (HIV)-hepatitis C (HCV) viruses coinfected patients was analyzed. A prospective cohort of 755 HIV-HCV coinfected patients who received their first anti-HCV therapy, based on interferon + ribavirin schemas, was evaluated. Incidence and histologic types of lymphomas were analyzed in two periods: (1) before administration of anti-HCV therapy and (2) after anti-HCV therapy. The association between lymphoma incidence and demographic, HIV- (minimum CD4+ cell count and CD4+ cell count at diagnosis of lymphoma, antiretroviral therapy, maximal HIV load and HIV load at diagnosis of lymphoma) and HCV-related variables (HCV load, genotype, sustained viral response to anti-HCV therapy) were analyzed. A total of 13 lymphomas [incidence rate (95% confidence interval), 0.72 (0.33-1.11) × 1000 person-years, time from HIV diagnosis to lymphoma diagnosis (median, interquartile range), 15 (11-19) years] were diagnosed. Nine of them were non-Hodgkin and four Hodgkin lymphomas. The median CD4+ T cell count at diagnosis of lymphoma was 457/mm3, with only two cases with values lower than 200/mm3. The incidence rate of non-Hodgkin lymphomas was similar pre- and post-anti HCV therapy [0.33 (0.00-0.65) vs 0.68 (0.08-1.26) × 1000 person-years, respectively, p > 0.05]. Patients with sustained virologic HCV response showed similar incidence rate of lymphomas than that of those without anti-HCV response. In conclusion, anti-HCV therapy does not modify the incidence rate of lymphomas in HIV-HCV coinfected patients.

Identification of Xenologs and Their Characteristic Low Expression Levels in the Cyanobacterium Synechococcus elongatus.

Horizontal gene transfer (HGT) is a central process in prokaryotic evolution. Once a gene is introduced into a genome by HGT, its contribution to the fitness of the recipient cell depends in part on its expression level. Here we show that in Synechococcus elongatus PCC 7942, xenologs derived from non-cyanobacterial sources exhibited lower expression levels than native genes in the genome. In accord with our observation, xenolog codon adaptation indexes also displayed relatively low expression values. These results are in agreement with previous reports that suggested the relative neutrality of most xenologs. However, we also demonstrated that some of the xenologs detected participated in cellular functions, including iron starvation acclimation and nitrate reduction, which corroborate the role of HGT in bacterial adaptation. For example, the expression levels of some of the xenologs detected are known to increase under iron-limiting conditions. We interpreted the overall pattern as an indication that there is a selection pressure against high expression levels of xenologs. However, when a xenolog protein product confers a selective advantage, natural selection can further modulate its expression level to meet the requirements of the recipient cell. In addition, we show that ORFans did not exhibit significantly lower expression levels than native genes in the genome, which suggested an origin other than xenology.

[Syphilis and human immunodeficiency virus infection: an endemic infection in men who have sex with men]. / Sífilis e infección por el virus de la inmunodeficiencia humana: una endemia en hombres que tienen sexo con hombres.

OBJECTIVE: to analyse epidemiological, clinical, and analytical features of HIV-infected men who have sex with men (MSM) diagnosed with syphilis in the Infectious Diseases Unit (Hospital Virgen de la Victoria, Málaga, Spain) during 2004-2013. PATIENTS AND METHODS: An observational study was conducted on 196 syphilis episodes in 167 MSM infected with HIV (2004-2013). Epidemiological, clinical, and analytical data were collected. Annual syphilis incidence among HIV-MSM is calculated as the number of syphilis episodes among MSM in one year divided by the number of MSM followed up in that year. RESULTS: Incidence ranged from 1.2% (2007) to 7.8% (2012). There were asymptomatic episodes in 42.8% cases, and an HIV-syphilis coincident diagnosis in 28.5%. CONCLUSIONS: The annual incidence of syphilis has increased within HIV infected MSM. One third of the syphilis episodes were simultaneous to HIV diagnosis and near half of them were asymptomatic.

Somatotype Analysis of International Football Players with Cerebral Palsy: A Comparison with Non-Disabled Football Players.

Football for people with cerebral palsy is a para-sport involving ambulant athletes with impairments, such as hypertonia, ataxia, or athetosis. The objective of the present study was to describe the somatotype of a representative sample of international football players according to different functional profiles of cerebral palsy, including spastic diparesis, athetosis/ataxia, spastic hemiparesis, and minimum impairment criteria, and to compare it with non-disabled football players. A total of 144 international para-footballers and 39 non-disabled footballers participated in the study, and their somatotype was calculated using anthropometric measurements. A Kruskal-Wallis test was used to compare the groups to determine and assess the differences between the different functional profiles, and the analysis of anthropometric variables and body composition showed no differences. Regarding somatotype, a predominance of the mesomorphic component was observed in all subgroups, and differences in somatotype were also found between non-disabled footballers and para-footballers with spastic hemiparesis and minimum impairment criteria. This study suggests that there may be a degree of homogeneity in terms of somatotype among footballers with or without physical impairments, such as hypertonia, athetosis, or ataxia. Furthermore, it provides reference values of international-level para-football players for the different sport classes, which can help coaches and trainers monitor athletes' physical conditions.

Detection of M2-Type Anti-Mitochondrial Autoantibodies against Specific Subunits in the Diagnosis of Primary Biliary Cholangitis in Patients with Discordant Results.

BACKGROUND: M2-type anti-mitochondrial autoantibodies are considered the hallmark of primary biliary cholangitis and are directed mainly against the E2 subunits of the 2-oxo acid dehydrogenase complex enzymes (PDC, BCOADC and OGDC). The aim of this study was to determine whether a Dot-blot that includes these E2 subunits separately could confirm the results of methods with non-separated subunits in patients with low positive or discordant results between techniques. METHODS: Sera of 24 patients with low positive or discordant results and of 10 patients with clear positive results by non-separated subunits methods were analyzed by Dot-blot with separated subunits. RESULTS: Autoantibodies against E2 subunits of PDC, BCOADC or OGDC were detected in all patients, except in one case from the low positive or discordant results group, by Dot-blot with separated subunits. CONCLUSIONS: It would be advisable to use methods that include the three E2 subunits, and a Dot-blot with separated subunits could confirm doubtful cases by non-separated assays.

Unusual Surge of Acute Hepatitis A Cases in 2016 and 2017 in Malaga, Southern Spain: Characterization and Relationship with Other Concurrent European Outbreaks.

We aimed to describe the Hepatitis A virus (HAV) cases that arose in Malaga (Spain) in 2016 and 2017 when the European Centre for Disease Prevention and Control (ECDC) reported several outbreaks among men who have sex with men (MSM). Therefore, we conducted a retrospective study gathering demographic, clinical, and immunological data from the acute HAV patients attending our hospital between March 2016 and December 2017. Additionally, VP1/P2A region was amplified from serum samples, sequenced, and genotyped. We finally performed a phylogenetic analysis, including the HAV strains from the other European outbreaks. A total of 184 HAV cases were reported, with the highest number in March 2017. The cohort mostly comprised Spaniards (81.0%), males (84.8%), and MSM (72.3%), with a median age of 33.0 years (interquartile range (IQR) = 25.0-43.0). Most patients exhibited symptoms. In addition, a successful amplification and sequencing of the VP1/P2A region was performed in 25 out of 106 serum samples (23.6%). All the sequences belonged to the genotype IA, and 20 were phylogenetically related to VRD_521_2016, first described in the United Kingdom (UK). In conclusion, HAV cases emerged in Malaga in 2016 and 2017, showing an epidemic character phylogenetically related to the predominant strain first detected in the UK. Characteristics of the cohort were similar to those from the European outbreaks.

Metabolic stasis in an ancient symbiosis: genome-scale metabolic networks from two Blattabacterium cuenoti strains, primary endosymbionts of cockroaches.

BACKGROUND: Cockroaches are terrestrial insects that strikingly eliminate waste nitrogen as ammonia instead of uric acid. Blattabacterium cuenoti (Mercier 1906) strains Bge and Pam are the obligate primary endosymbionts of the cockroaches Blattella germanica and Periplaneta americana, respectively. The genomes of both bacterial endosymbionts have recently been sequenced, making possible a genome-scale constraint-based reconstruction of their metabolic networks. The mathematical expression of a metabolic network and the subsequent quantitative studies of phenotypic features by Flux Balance Analysis (FBA) represent an efficient functional approach to these uncultivable bacteria. RESULTS: We report the metabolic models of Blattabacterium strains Bge (iCG238) and Pam (iCG230), comprising 296 and 289 biochemical reactions, associated with 238 and 230 genes, and 364 and 358 metabolites, respectively. Both models reflect both the striking similarities and the singularities of these microorganisms. FBA was used to analyze the properties, potential and limits of the models, assuming some environmental constraints such as aerobic conditions and the net production of ammonia from these bacterial systems, as has been experimentally observed. In addition, in silico simulations with the iCG238 model have enabled a set of carbon and nitrogen sources to be defined, which would also support a viable phenotype in terms of biomass production in the strain Pam, which lacks the first three steps of the tricarboxylic acid cycle. FBA reveals a metabolic condition that renders these enzymatic steps dispensable, thus offering a possible evolutionary explanation for their elimination. We also confirm, by computational simulations, the fragility of the metabolic networks and their host dependence. CONCLUSIONS: The minimized Blattabacterium metabolic networks are surprisingly similar in strains Bge and Pam, after 140 million years of evolution of these endosymbionts in separate cockroach lineages. FBA performed on the reconstructed networks from the two bacteria helps to refine the functional analysis of the genomes enabling us to postulate how slightly different host metabolic contexts drove their parallel evolution.

Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients.

The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress.

A Narrative Review about Autism Spectrum Disorders and Exclusion of Gluten and Casein from the Diet.

OBJECTIVE: Autism spectrum disorders (ASDs) appear in the early stages of neurodevelopment, and they remain constant throughout life. Currently, due to limitations in ASDs treatment, alternative approaches, such as nutritional interventions, have frequently been implemented. The aim of this narrative review is to gather the most relevant and updated studies about dietary interventions related to ASDs etiopathogenesis. RESULTS: Our literature search focused on the gluten- and casein-free (GFCF) diet. The literature found shows the inexistence of enough scientific evidence to support a general recommendation of dietary intervention in children with ASD. Protocols and procedures for assessing risk and safety are also needed. Future lines: Prospective and controlled research studies with larger sample sizes and longer follow-up times are scarce and needed. In addition, studies considering an assessment of intestinal permeability, bacterial population, enzymatic, and inflammatory gastrointestinal activity are interesting to identify possible responders. Besides brain imaging techniques, genetic tests can also contribute as markers to evaluate the comorbidity of gastrointestinal symptoms.

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942.

BACKGROUND: Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. RESULTS: By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. CONCLUSIONS: Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.

Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients.

The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress.

A Pandemic within Other Pandemics. When a Multiple Infection of a Host Occurs: SARS-CoV-2, HIV and Mycobacterium tuberculosis.

By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/µL diagnosed in a high-income country: a multicentre cohort study.

OBJECTIVES: The World Health Organization recommends routinely screening HIV-infected patients with CD4+ T-cell counts <100/µL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain. METHODS: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4+ T-cell counts ≤100/µL at the time of plasma collection and a follow-up >4 weeks, unless they died. RESULTS: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114. CONCLUSIONS: The CrAg+ prevalence among HIV-infected patients with CD4+ T-cell counts ≤100/µL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.

Anthropometrical Features of Para-Footballers According to Their Cerebral Palsy Profiles and Compared to Controls.

Cerebral palsy (CP) football is a team para-sport practiced by para-athletes with eligible impairments of hypertonia, athetosis, and ataxia. This study aimed: (1) to describe the anthropometrical and body composition profiles of international CP para-footballers with different CP profiles (i.e., spastic diplegia, athetosis/ataxia, spastic hemiplegia, and minimum impairment); (2) to analyze the differences between both affected/nondominant and nonaffected/dominant sides; and (3) to compare the sample of international-level CP para-footballers (n = 141) with a sample of highly trained able-bodied footballers (n = 39). Anthropometric measures included four breadths, nine girths, and six skinfolds, while body composition was measured through fat mass (including Carter's, Faulkner's, and Withers' equations), muscle mass (Lee's equation), and bone mass (Rocha's and Martin's equations). This study found differences between the able-bodied footballers and the following impairment profiles: spastic diplegia (skinfolds); ataxia/athetosis (corrected calf of the nondominant side, and calf skinfolds for both sides); and spastic hemiplegia (all measurements excepting femur breadth, and thigh and ankle girths). No differences were found between para-athletes with minimum impairment and the able-bodied footballers. This study demonstrates that football players with or without physical impairments of hypertonia athetosis or ataxia may be considered homogeneous in shape when dominant size is compared. Besides, the study provides reference scores on anthropometric measures and body composition of international-level CP para-footballers that can help sports coaches and physical trainers to monitor physical fitness of their para-athletes.

High Prevalence of Sequences Included in Transmission Clusters Within Newly Diagnosed HIV-1 Patients in Southern Spain (2004-2015).

The presence of transmission clusters (TCs) and their epidemiological characteristics in a treatment-naive cohort of HIV-1 patients in southern Spain over a decade (2004-2015) were evaluated. Protease and reverse transcriptase sequences provided by each genotype test were used in the phylogenetic study, performed first by the neighbor-joining method and then confirmed by Bayesian analysis. We collected clinical, immunovirological, and demographic data for all patients included. Our cohort comprised 757 patients, 428 (56.5%) belonging to a TC. Overall, we found 123 TCs, 21 of them comprising five or more individuals and three with ≥10 sequences. Forty-three TCs (35.0%) remained active. The clustered patients were mainly men (92.8%) who had sex with men (MSM) (81.5%), Spanish (80.6%), and young adults (median age at diagnosis of 32.6 years). They had lower percentages of late diagnosis and AIDS cases (42.1% and 13.6%, respectively), whereas the presence of recent seroconverters (31.1%), HIV-1 B subtypes (79.4%), and transmission drug resistance (20.3%) increased within TCs, with regard to not-clustered individuals. Among the TCs of non-B variants, circulating recombinant forms (CRF) were predominant (87.5%), with the highest frequencies for CRF19_cpx (17.0% of non-B subtype sequences in TCs); CRF02_AG (15.9%); and CRF01_AE (9.1%). In conclusion, over half of our cohort was included within a TC. More than a third of TCs found could be considered active transmission events. Belonging to a TC was related to MSM, Spanish origin, recent seroconversion, high prevalence of resistance mutations, and B HIV subtype. Among the non-B genetic forms in TCs, we found a high prevalence of CRF19_cpx, CRF02_AG, and CRF01_AE variants.

Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain.

BACKGROUND: CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data. RESULTS: Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded. CONCLUSIONS: We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients / Efecto sinérgico del síndrome metabólico y la lipodistrofia en el estrés oxidativo y el proceso de inflamación en pacientes con VIH que reciben tratamiento

The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress.(AU)

El objetivo de este estudio fue evaluar el efecto de la lipodistrofia (LD) asociada al síndrome metabólico (SM) en el estrés oxidativo y la inflamación en una cohorte de 243 pacientes con VIH y SM, todos en tratamiento con pautas antirretrovirales diferentes. Recopilamos datos inmunovirológicos, bioquímicos y metabólicos, así como medidas antropométricas. Además, el riesgo cardiovascular también se evaluó mediante el índice de plasma aterogénico (API) y la puntuación de riesgo de Framingham. El grupo de pacientes con SM-LD se caracterizó por un recuento inicial de linfocitos CD4 y una relación CD4/CD8 inferiores y una carga vírica inicial más alta que el grupo sin LD. También observamos peores perfiles lipídicos y glucémicos (con menor colesterol HDL y niveles más altos de triglicéridos y glucosa) en el grupo de SM-LD. El IMC, la presión arterial sistólica y la puntuación de Framingham aumentaron significativamente en comparación con el grupo de SM-sin LD. Además, los pacientes con SM y LD tenían niveles significativamente más altos de proteínas carboniladas, peroxidación lipídica, IL-6 e IL-8, así como una disminución significativa de los niveles de leptina, adiponectina y actividades antioxidantes de la catalasa, superóxido dismutasa y enzimas asociadas al glutatión. En los pacientes con SM-LD VIH-1, se observó una correlación negativa significativa entre la puntuación de riesgo de Framingham y los biomarcadores antioxidantes, sin embargo, se observó una asociación positiva entre el API y la proteína C reactiva y las proteínas carboniladas. Al segregarse por ART, las condiciones mencionadas anteriormente fueron peores en el grupo de SM-LD, cuyo tratamiento incluía inhibidores de la proteasa, como el lopinavir. En conclusión, los pacientes con VIH-1 tratados durante al menos seis meses, especialmente con pautas que incluían IP, mostraron un empeoramiento del proceso inflamatorio y el estrés oxidativo.(AU)

Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men who have sex with men be recommended?

INTRODUCTION: Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition (1). It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors. MATERIALS AND METHODS: Prospective study of a cohort of asymptomatic HIV-MSM with follow-up in Malaga (southern Spain) during October 2012-May 2014. Patients with an opportunistic event or who received active antibiotic therapy for CT and/or NG in the previous month were excluded. All of them completed a questionnaire about sexual behaviour, barrier methods and recreational drugs use. Demographical, epidemiological, clinical, analytical and therapeutic data were also collected. Pharyngeal and rectal swabs, and urine samples were collected to be tested for CT and NG by nucleic acid amplification test (c4800 CT/NG. Roche Diagnostics, Mannheim, Germany) (3). STATISTICS ANALYSIS: SPSS 17.0. RESULTS: 255 patients were asked to participate and 248 of them accepted. Median age was 37.7 (30.6-46.3) years, median time since HIV diagnosis was 47.7 (10.5-104.1) months, and median CD4 cells count was 607 (440-824) cell/µL. There were 195 (78.6%) patients on antiretroviral therapy; 81.5% of them had undetectable viral load. 80.5% of the patients had a past history of STI. Infection by CT and/or NG was diagnosed in 24 (9.7%) patients. Overall four urine samples, two pharyngeal, and 15 rectal ones were positive for CT, and five pharyngeal and five rectal swabs were positive for NG. Two patients were co-infected by CT and NG: one with CT in urine and both in rectum, another with CT in urine and rectum and NG in pharynx. One patient presented CT in pharynx and rectum, and two patients NG in pharynx and rectum. Positive CT and/or NG tests were only related with detectable HIV viral load (OR 3.08, 95% CI 1.2-7.4; p=0.01). It was not related with sexual behaviour, nor with alcohol or recreational drugs use. CONCLUSIONS: STI screening had a great acceptance in this population. There was a high prevalence of asymptomatic CT and/or NG infections. Rectum sample was the most effective one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM.