Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316).

BACKGROUND: Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies. OBJECTIVES: Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens. METHODS: A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent. RESULTS: Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes. CONCLUSIONS: No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.

Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Impact of hypochloremia as a prognostic factor in patients with heart failure, a retrospective cohort study.

BACKGROUND: some studies suggest that hypochloremia is a risk factor in the prognosis of heart failure (HF) in patients with recent decompensation. MATERIALS AND METHODS: retrospective cohort study of patients discharged due to HF decompensation who began follow-up in a specialized clinic. Two groups are defined: patients with hypochloremia (chloride < 98 mmol/L) and normochloremic patients (chloride > 98 mmol/L) in the initial assessment within the first month after discharge. The rate of intravenous diuretic rescue, emergency department visits, readmission for HF and cardiovascular (CV) death are compared using a Cox proportional hazards model. RESULTS: 165 patients were included (59% women, mean age 85 years), with 60 (36%) having hypochloremia. Both groups were comparable in terms of baseline characteristics, except for female sex, presence of peripheral artery disease, moderate-to-severe liver disease (more prevalent in the hypochloremia group), PROFUND index, and baseline furosemide dose (higher in patients with hypochloremia). The incidence of the primary event was higher in subjects with hypochloremia than in normochloremic subjects (HR: 1.59, 95% CI 0.97-2.62), mainly due to the need for intravenous diuretic rescue (HR: 1.86, 95% CI 1.07-3.24). CONCLUSIONS: hypochloremia following admission for HF decompensation is associated with a greater need for intravenous diuretic rescue therapy and probably worse overall prognosis across the spectrum of the disease, regardless of left ventricular ejection fraction (LVEF).

Retinal vein occlusion. Audit of a specialized care program.

BACKGROUND AND OBJECTIVES: Retinal vein occlusion (RVO) is the second most frequent cause of retinal vascular disease and is related to classic cardiovascular risk factors. A specific program was designed to detect and treat risk factors in patients with RVO. The aim of this study is to audit the results of this program. PATIENTS AND METHODS: The program consisted of a multidisciplinary clinical evaluation by the Ophthalmology and Internal Medicine Departments. All patients with RVO were screened, at minimum, for hypertension, diabetes, dyslipidemia, smoking, overweight, and antiphospholipid syndrome. New risk factors or poor control of known risk factors were expected to be found in at least one-third of the patients. Among them, therapeutic measures were expected to be taken in at least two-thirds. A dissociated automated search of the data of all patients who entered the program between April 2021 and April 2022 was performed. RESULTS: Fifty-six patients were included for analysis. Of these, 39 (69.6%) had at least one new or poorly controlled risk factor and 43 (76.8%) had their treatment modified in some way. Antiphospholipid syndrome was detected in five (8.9%). Only one patient had low-risk hereditary thrombophilia. After an exhaustive examination, no risk factors were found in 11 patients. CONCLUSION: This specific program has been effective in detecting new or poorly controlled risk factors and improving their treatment.

Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions.

BACKGROUND: Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. OBJECTIVE: The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. METHODS: SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. RESULTS: A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/µL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were -13 mg/dL (-7%; P<0.0001), -19 mg/dL (-13%; P<0.0001) and -7 mg/dL (-6%; P=0.021), respectively. CONCLUSIONS: In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

Phenotypic modulation of cultured vascular smooth muscle cells: a functional analysis focusing on MLC and ERK1/2 phosphorylation.

Primary cultures of vascular smooth muscle cells (VSMCs) from rats offer a good model system to examine the molecular basis of mechanism of vascular contraction-relaxation. However, during pathological conditions such as atherosclerosis and hypertension, VSMCs characteristically exhibit phenotypic modulation, change from a quiescent contractile to a proliferative synthetic phenotype, which impairs this mechanism of vascular contraction-relaxation. Taking in account that Myosin light chain (MLC) and ERK1/2 directly participate in the process of vascular contraction, the aim of the current study was to analyze the involvement of MLC and ERK1/2 signaling during the process of VSMCs phenotypic modulation. Primary cultures of VSMCs from rat thoracic aortas were isolated and submitted to different number of passages or to freezing condition. Semi-quantitative RT-PCR was used to evaluate the mRNA levels of VSMCs differentiation markers, and western blot assays were used to determine the MLC and ERK1/2 phosphorylation levels during VSMCs phenotypic modulation. Also, immunocytochemical experiments were performed to evaluate morphological alterations occurred during the phenotypic modulation. Elevated number of passages (up to 4) as well as the freezing/thawing process induced a significant phenotypic modulation in VSMCs, which was accompanied by diminished MLC and ERK1/2 phosphorylation levels. Phosphorylation of MLC was suppressed completely by the treatment with a synthetic inhibitor of MEK-1, a direct upstream of ERK1/2, PD98059. These findings provide that ERK1/2-promoted MLC phosphorylation is impaired during VSMCs phenotypic modulation, suggesting that ERK1/2 signaling pathway may represent a potential target for understanding the pathogenesis of several vascular disease processes frequently associated to this condition.

[Evaluation of 2 tuberculosis chemoprophylaxis regimens in patients infected with human immunodeficiency virus. The GECMEI Group]. / Evaluación de dos pautas de quimioprofilaxis tuberculosa en pacientes infectados por el virus de la inmunodeficiencia humana. Grupo GECMEI.

OBJECTIVE: To assess the compliance, tolerance and efficacy of a short chemoprophylaxis regimen (IR) for tuberculosis using isoniazid (INH) plus rifampin (RIF) during 3 months versus a standard regimen (I) of isoniazid during 12 months in HIV positive patients. MATERIAL AND METHODS: Prospective, comparative, randomized and open clinical trial in four general hospitals and one prison hospital of Castilla-La Mancha. Prophylaxis was administered to PPD-positive patients and to anergic patients according to the CDC recommendations (1991). Patients were randomized in two treatment groups: regimen IR, isoniazid 300 mg daily and rifampin 600 mg daily; regimen I, isoniazid 300 mg during 12 months. RESULTS: 133 patients were included, 64 to regimen I and 69 to regimen IR. Regimen IR had a better tolerance with a 28% of adverse effects versus 55% in regimen I. Hepatotoxicity was more frequent in regimen I with a RR = 2.2 (CI 95% 1.23-4.01). Severe hepatotoxicity leading to treatment withdrawal was related to drug administration time and was more frequent in the 12 months regimen group. Short regimen showed a better compliance, without significant differences. Tuberculosis incidence rate was a 4.23 cases/100 persons--year for regimen I and 2.08 in regimen IR, with a relative risk for developing tuberculosis with regimen IR group of 0.51 (CI 95% 0.09-2.8) versus regimen I group, without statistical significance. Prison stay was associated to a significant risk for tuberculosis, regardless of both regimens (RR = 9.2 CI 95%, 1.06-80.2). CONCLUSIONS: In HIV-infected patients with PPD(+) or anergic, regimen with IR is at least as effective as regimen I for preventing the development of tuberculous disease, and has less adverse effects.

Therapeutic implications of peptide interactions with G-protein-coupled receptors in diabetic vasculopathy.

The dramatic worldwide increase in the prevalence of diabetes has generated an attempt by the scientific community to identify strategies for its treatment and prevention. Vascular dysfunction is a hallmark of diabetes and frequently leads to the development of atherosclerosis, coronary disease-derived myocardial infarction, stroke, peripheral arterial disease and diabetic 'triopathy' (retinopathy, nephropathy and neuropathy). These vascular complications, developing in an increasingly younger cohort of patients with diabetes, contribute to morbidity and mortality. Despite the development of new anti-diabetic or anti-hyperglycaemic drugs, vascular complications remain to be a problem. This warrants a need for new therapeutic strategies to tackle diabetic vasculopathy. There is a growing body of evidence showing that peptide-binding G-protein-coupled receptors (peptide-binding GPCRs) play an important role in the pathophysiology of vascular dysfunction during diabetes. Thus, in this review, we discuss some of the peptide-binding GPCRs involved in the regulation of vascular function that have potential to be a therapeutic target in the treatment of diabetic vasculopathy.

HALLAZGO DE CESTODOS DE LA FAMILIA HYMENOLEPIDIDAE EN EL RATÓN ALGODONERO DEL SUR (Sigmodon hirsutus) EN HUILA, COLOMBIA / CESTODES OF HYMENOLEPIDIDAE FAMILY FOUND IN THE SOUTHERN COTTON RAT (Sigmodon hirsutus) IN HUILA, COLOMBIA

El estudio de la fauna parasitológica de roedores silvestres constituye una clave importante para enfrentar situaciones de riesgo en salud pública, conservación y producción animal, debido al impacto que algunos de estos parásitos pueden producir en la salud de seres humanos, animales silvestres y animales de producción y compañía. En mayo de 2011 se colectaron muestras de materia fecal de ratones silvestres en los municipios de Garzón y El Agrado (Huila, Colombia), con el fin de identificar, mediante evaluación coprológica, las especies de parásitos gastrointestinales presentes en roedores de dicha zona. Se capturaron siete ratones de la especie Sigmodon hirsutus, se tomaron muestras de materia fecal y los animales fueron liberados posteriormente. En las muestras se observaron huevos de la familia Hymenolepididae, con características morfológicas que los ubican en los géneros Hymenolepis o Rodentolepis. El hallazgo de estos parásitos en las heces de roedores silvestres en áreas de hábitat compartido con seres humanos sugiere un factor de riesgo zoonótico. Sin embargo, se requieren investigaciones adicionales que permitan establecer asociación entre el parasitismo gastrointestinal en humanos y la presencia de roedores en el área de estudio.

The study of parasitological fauna of wild rodents constitutes a significant key to confront situations of risk on public health, conservation and animal production, due to the impact of some parasites on the health of humans, wildlife, farm animals and pets. Fecal samples of wild rodents were collected in May 2011 in the area of Garzón and El Agrado, (Huila, Colombia) in order to identify, by parasitological examination, the species of gastrointestinal parasites found in rodents in this area. Seven mices of specie Sigmodon hirsutus, were trapped in order to take fecal samples. Animals were released after this procedure. Eggs of cestodes of the family Hymenolepididae with morphological characteristics of genera Hymenolepis or Rodentolepis were found in the samples. The finding of these parasites in the feces of wild rodents in areas of shared habitat with humans suggests a zoonotic risk factor, but it is necessary to carry out more researches on association between gastrointestinal parasitism in humans and presence of wild rodents in the area.

[Prevalence of IgG antibodies against Cytomegalovirus in patients with angiographically demonstrated coronary atherosclerosis]. / Prevalencia de anticuerpos IgG frente a Citomegalovirus en pacientes con aterosclerosis coronaria demostrada angiográficamente.

BACKGROUND: Over the past 25 years the potential role of herpesvirus and particularly Cytomegalovirus as a factor which contribute to atherogenesis, and more recently in restenosis, has been investigated. OBJECTIVES: To determine the rate of Cytomegalovirus seropositivity in patients with angiographically demonstrated Coronary Artery Atherosclerosis. PATIENTS AND METHODS: The subjects were all adult patients undergoing coronary angiography at the Hospital Virgen de la Salud, Toledo between February, 1997 and May, 1998. From each patient, blood was drawn and collected to be assayed. Also we collected the data from sex, age, classic risk factors for coronary artery disease (hypertension, hypercholesterolemia, diabetes and cigarette smoking) and catheterization. Data from 437 patients who underwent cardiac catheterization were collected. There was 349 (82.3%) patients who underwent catheterization because of Ischemic Heart Disease. SEROLOGIC ASSAYS: Serum IgG antibodies to cytomegalovirus were measured quantitatively with EIA, VIDAS, (bioMérieux). As recommended by the manufacturer a titer over 6 was considered positive. RESULTS: There was 115 female and 319 males. Patients were 24-86 years old. Data from catheterization showed that 113 patients (26%) have no lesions on coronaryography and 321 patients (74%) have Coronary Artery Disease (CAD). The rate of Cytomegalovirus-seropositive was 97.1% in patients with lesions and 98.2% in those without lesions. CONCLUSIONS: There is a high rate of antibodies positive for Cytomegalovirus in the population, in patients with Ischemic Heart Disease and with coronary artery disease as in those without lesions in the coronarigraphy. Our conclusion is that if Cytomegalovirus could have any role in the building of proliferating ateheromas and in view of seroepidemiological studies some other factors must be implicated in the development of plaque growth.

Treatment of human brucellosis with netilmicin and doxycycline.

We conducted a prospective, noncomparative, multicenter study to assess the safety and efficacy of doxycycline and netilmicin in the treatment of human brucellosis. The study included 64 patients who had acute brucellosis without endocarditis or neurobrucellosis. The treatment schedule consisted of the administration of 100 mg of doxycycline (or 5 mg/[kg.d] if body weight < or = 40 kg) twice a day orally for 45 days, plus 300 mg of netilmicin (6 mg/[kg.d] if body weight < or = 50 kg) intramuscularly once daily for 7 days. Therapeutic failure was noted in 5 patients (7.7%; 95% confidence interval [CI], 2.5%-17.1%), of whom 2 had spondylitis, 1 had sacroiliitis, and 1 had a splenic abscess that required splenectomy. Relapse was noted in eight patients (12.5%; 95% CI, 5.6%-23.2%). When relapse was considered in combination with initial lack of efficacy, 13 patients (21.9%; 95% CI, 12.3%-33.9%) failed to respond to therapy. Fifteen patients (23%; 95% CI, 13.5%-35.2%) had adverse effects, and one patient (1.5%) had a treatment-limiting adverse effect. Combination therapy with netilmicin/doxycycline may be effective in treating acute brucellosis. However, prospective controlled trials must confirm these results.

Doxycycline-rifampin versus doxycycline-streptomycin in treatment of human brucellosis due to Brucella melitensis. The GECMEI Group. Grupo de Estudio de Castilla-la Mancha de Enfermedades Infecciosas.

Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined. We have carried out a multicenter, open, controlled trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis. The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis. The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74). Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%)(P = 0.10). Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02). When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy was well tolerated and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P> 0.2). We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.