Prevalence of and risk factors for low bone mineral density in Spanish treated HIV-infected patients.

OBJECTIVES: Several studies have involved antiretroviral therapy in the pathogenesis of low bone mineral density (BMD), while others have not confirmed this association. In this study we analyze the impact of HIV status, traditional risk factors and antiretroviral therapy in BMD in an HIV-infected population living in Madrid. MATERIAL AND METHODS: We performed a cross-sectional analysis of 107 individuals infected with HIV and exposed to antiretroviral treatment to estimate the prevalence of decreased BMD. Bone mineral density of lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. In a multivariate analysis variables related with HIV status, antiretroviral drugs and traditional risk factors were included. RESULTS: Low BMD was diagnosed in 63 participants (58.9%), including osteoporosis in 11 (10%). At least one cause of osteoporosis was identified in 43 patients (40%), with a deficiency of vitamin D in 86 (89%) and secondary hyperparathyroidism in 30 (28%). In multivariate analysis, increasing age, a treatment based on boosted PI and tenofovir DF, and previous exposure to tenofovir were identified as independent risk factors for a decreased BMD in both lumbar spine and femoral neck. CONCLUSIONS: We have confirmed a high prevalence of reduced BMD, which is favoured by ritonavir-boosted PI and TDF. Bone safety should continue to be evaluated in clinical trials and cohort studies in order to demonstrate that the new drugs offer additional advantages regarding the impact on BMD.

Depressive symptoms in early- and late-onset older bipolar patients compared with younger ones.

OBJECTIVES: The aim of this study was to determine clinical and outcome differences between older bipolar patients with early onset (EO) and late onset (LO) of the illness and between younger and EO older patients with a bipolar disorder under long-term treatment in an outpatient clinical setting. METHODS: Three hundred ninety-five bipolar I and II outpatients were followed up for up to 7.7 years. Of these, 213 younger (<50 years) and 88 older (>60 years) patients were included. In the older subsample, 50 EO patients (onset <50 years) versus 38 LO patients (≥50 years) were analyzed. Likewise, younger versus EO older patients were compared. RESULTS: The likelihood of LO older patients of being bipolar II was higher than for EO older patients. They were also diagnosed earlier than EO older patients. No other clinical differences at baseline and at the prospective follow-up were found. Compared with younger patients, EO older patients had more frequent depressive symptoms at baseline, suffered more major depressive episodes in the previous year and in the prospective follow-up, received more antidepressants at baseline, had higher rates of medical comorbid conditions and were less likely to be tobacco smokers. CONCLUSIONS: Older patients constitute a meaningful proportion of bipolar patients under treatment. EO older patients suffered significantly from more frequent depressive symptoms than younger ones. LO older patients were predominantly bipolar II. So as bipolar illness progressed, depressive symptomatology became more frequent and manic episodes were less severe. Copyright © 2016 John Wiley & Sons, Ltd.

[Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir]. / Factores predictivos de las interacciones farmacológicas clínicamente significativas en los pacientes tratados con regímenes basados en inhibidores de proteasa, inhibidores de transcriptasa inversa no nucleósidos y raltegravir.

BACKGROUND AND OBJECTIVE: To determine the prevalence and types of clinically significant drug-drug interactions (CSDI) in the drug regimens of HIV-infected patients receiving antiretroviral treatment. DESIGN: retrospective review of database. Centre: Hospital Universitario Severo Ochoa, Infectious Unit. PARTICIPANTS: one hundred and forty-two participants followed by one of the authors were selected from January 1985 to December 2014. DATA COLLECTION: from their outpatient medical records we reviewed information from the last available visit of the participants, in relation to HIV infection, comorbidities, demographics and the drugs that they were receiving; both antiretroviral drugs and drugs not related to HIV infection. We defined CSDI from the information sheet and/or database on antiretroviral drug interactions of the University of Liverpool (http://www.hiv-druginteractions.org) and we developed a diagnostic tool to predict the possibility of CSDI. By multivariate logistic regression analysis and by estimating the diagnostic performance curve obtained, we identified a quick tool to predict the existence of drug interactions. RESULTS: Of 142 patients, 39 (29.11%) had some type of CSDI and in 11.2% 2 or more interactions were detected. In only one patient the combination of drugs was contraindicated (this patient was receiving darunavir/r and quetiapine). In multivariate analyses, predictors of CSDI were regimen type (PI or NNRTI) and the use of 3 or more non-antiretroviral drugs (AUC 0.886, 95% CI 0.828 to 0.944; P=.0001). The risk was 18.55 times in those receiving NNRTI and 27,95 times in those receiving IP compared to those taking raltegravir. CONCLUSIONS: Drug interactions, including those defined as clinically significant, are common in HIV-infected patients treated with antiretroviral drugs, and the risk is greater in IP-based regimens. Raltegravir-based prescribing, especially in patients who receive at least 3 non-HIV drugs could avoid interactions.

[Aging and influence of inversion of the CD4:CD8 ratio in the incidence of co-morbidities and mortality in a cohort of patients infected with human immunodeficiency virus]. / Envejecimiento e influencia de la inversión del cociente CD4/CD8 en la incidencia de las comorbilidades y mortalidad de una cohorte de pacientes infectados por el virus de inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: It has been postulated that the inversion of the CD4:CD8 ratio as a hallmark of immunosenescence can be an independent factor that can herald the risk of co-morbidities. We studied the influence of aging and inversion of the CD4:CD8 ratio in the incidence of comorbidities and mortality in the cohort of Hosptital Severo Ochoa. METHODS: We analyzed the differences in the incidence rates of age-adjusted morbidities and evaluated the inversion of the CD4:CD8 ratio as predictor of mortality and development of comorbidities. RESULTS: Age was associated with an increased incidence rate of diabetes mellitus, fractures, COPD and non-AIDS malignancies. We found an increased incidence rate of non-AIDS clinical events (OR 2.25; 95% CI 1.025-4.94) and AIDS events (OR 3.48; 95% CI 1.58-7.64) in individuals with CD4:CD8 ratio<0.7. Moreover, patients with a CD4:CD8 ratio<0.7 ratio had a higher risk of mortality (OR 5.96; 95% CI 0.73 to 48.40). CONCLUSION: It is important to detect and prevent non-AIDS comorbidities in the presence of a CD4:CD8 ratio<0.7.

Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy.

We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

Seasonality, smoking and history of poor treatment compliance are strong predictors of dropout in a naturalistic 6 year follow-up of bipolar patients.

Bipolar disorder is a highly recurrent disease which requires long-term treatment. Dropout is a major problem, poorly understood. The objectives of this study were to know the risk of dropout of a cohort of bipolar patients under ambulatory treatment and to identify the clinical profile of patients more likely to abandon the follow-up. A sample of 285 BD I and II patients was followed up for a mean of 2.87 years. A significant proportion of patients failed regular follow-up. The dropout rates were 6.3 % at three months, 12.7 % at 6 months, and 17.6, 27.2, 37.3, 44.0, 47.2 and 49.0 % at 1, 2, 3, 4, 5 and 6 years respectively. Very few variables at baseline predicted dropout. Patients under 35 years of age were more likely to dropout than older cases. Seasonality, smoking and specially history of poor treatment compliance were strong predictors of dropout. Given the magnitude of dropout, additional early clinical interventions should be considered for high-risk patients.

Prevalence of vitamin D deficiency and its related risk factor in a Spanish cohort of adult HIV-infected patients: effects of antiretroviral therapy.

We analyzed serum 25(OH) cholecalciferol [25(OH)D] levels and factors related to deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) in a cohort of Spanish HIV-infected patients and compared them with an age- and latitude-matched population from another study. We prospectively assessed 25(OH)D deficiency/insufficiency in a cohort of 352 HIV patients during 2009-2010. Predisposing factors were recorded and their relationship to low levels was assessed by logistic regression; a nutritional survey examined intake, nutritional status, and sunlight exposure in a subgroup of 92 patients. We studied the correlation of 25(OH)D with parathyroid hormone (PTH) and alkaline phosphatase. Age-, sex-, and race/ethnicity-adjusted vitamin D deficiency (<20 ng/ml) was 44.0% (95% CI, 38.8-49.4%) and insufficiency (<30 ng/ml) was 71.6% (95% CI, 66.9-76.3). Deficiency was 16.4% more prevalent in our sample than in non-HIV-infected Spaniards. Lower sunlight exposure was the only factor related to lower levels in the lifestyle and nutritional survey (p=0.045). In multiple logistic regression, higher body mass index (BMI), black race/ethnicity, lower seasonal sunlight exposure, men who have sex with men (MSM), and heterosexual transmission categories, efavirenz exposure and lack of HIV viral suppression were independently associated with deficiency/insufficiency. These variables predicted 79% of cases [AUC=0.872 (95% CI, 0.83-0.91)]. Patients receiving protease inhibitors (PIs) [OR 4.0 (95% CI, 1.3-12.3); p=0.014] or NNRTI [OR 3.6 (95% CI, 1.7-11.2); p=0.025] had higher odds of increased PTH levels; this was significant only in 25(OH)D-deficient patients (p=0.004). As in less insolated areas, the prevalence of vitamin D deficiency/insufficiency was high in HIV-infected patients in Spain; among treated patients, levels were higher with PIs than with efavirenz.

[Diagnostic delay and differences by sex and clinical subtype in a cohort of outpatients with bipolar disorder]. / Retraso diagnóstico y diferencias por sexo y subtipo clínico en una cohorte de pacientes ambulatorios con trastorno bipolar.

INTRODUCTION: We describe the clinical and sociodemographic features at baseline of a cohort of bipolar patients included in a prospective study. METHODS: A total of 296 consecutive outpatients with bipolar disorder were recruited. Diagnosis relied on clinical judgment according to DSM-IV-TR criteria and the semi-structured MINI Interview. Retrospective data on the course of the disease and cross-sectional data on social adaptation (Social Adaptation Adjustment Self-Assessment Scale (SASS) and affective symptoms were collected. Affective symptomatology (euthymia, subsyndromal symptoms and episodes) was studied according to clinical criteria and the Hamilton Depression and Young rating scales. Differences between type I and II bipolar patients and between men and women were analyzed. RESULTS: The mean age was 48.8 years (95% CI 47.2-50.4); 56.8% were women and 43.2% were men. A total of 65.2% had a diagnosis of type I bipolar disorder and 23.3% of type II; 49.8% of the sample were euthymic, 32.7% had subsyndromal symptoms and 17.5% had had an affective episode. Diagnostic delay was 9.3 years (95% CI 8.2-10.3). In patients with type II bipolar disorder, the mean age (54.4 years; 95% CI 50.9-57.9 vs. 47.7 years; 95% CI 45.8-49.7, p=0.007), age at onset of illness (35.7 years; 95% CI 31.8-39.7 vs. 29.8 years; 95% CI 28-31.6, p=0.008) and age at diagnosis (47.7 years; 95% CI 44-51.3 vs. 37.9; 95% CI 35.9-39.8, p<0.0001) were higher than in patients with type I bipolar disorder. Manic polarity in the initial episode and psychotic episodes were more frequent in men, while depressive episodes and hypothyroidism were more frequent in women. CONCLUSIONS: Our results confirm data published in our environment on sociodemographic and clinical variables but diagnostic delay in our study was longer. Compared with American samples, age at onset and at diagnosis were higher in our sample but comorbidity was much lower.

[Factors predicting the failure of interruption of highly active antiretroviral treatment (HAART) in HIV-infected patients]. / Factores que predicen el fracaso de las interrupciones del tratamiento antirretroviral (TAR) en los pacientes con infección por el VIH.

INTRODUCTION: Treatment interruptions may be an alternative to HAART in the management of chronically infected HIV-patients. We designed this study in an attempt to assess the predictability of this strategy. METHODS: We recruited HIV-infected patients whose treatment had been suspended. Interruption was due to the patient's own decision, or toxicity, or because the patient had started the treatment with more than 350 CD41 cells/microL (immunologic criteria). RESULTS: Forty-one consecutive patients were included, with a median follow-up of 13 months. Failure was associated with the reason for interruption (p 5 0.0063). Failure occurred in 14.3% of those who interrupted treatment due to immunological criteria and in 40% of those who interrupted treatment due to their own decision or toxicity. The reasons for interruption were: toxicity in 11 patients (26.8%), personal decision in 9 (21.9%) and immunological criteria in 21 (51.2%). In the univariate analysis, the nadir CD41 cell count < 350 cél./microL [OR 16 (p = 0.054)] was statistically significant in the patients who stopped treatment due to immunological criteria, while treatment with protease inhibitors [OR 14 (p = 0.032)] was statistically significant in the remaining patients. In the multivariable analysis only nadir CD41 < 350 cél./microL was independently related with failure. CONCLUSIONS: Failure was related to interruption criteria and was greater in patients who stopped due their own decision or toxicity. When interruption was due to immunological criteria, the factor predicting failure was nadir CD41 cell count < 350 cél./microL. In the remaining patients, none of the variables was related to failure.

Clostridium difficile colitis associated with valaciclovir.

OBJECTIVE: To report a case of Clostridium difficile colitis associated with valaciclovir treatment. CASE SUMMARY: A 73-year-old man with lumbar herpes-zoster started valaciclovir 1 g tid. After three days he began vomiting and developed diarrhea, three to four stools per day. Symptoms worsened over the following days and he was admitted. Valaciclovir was stopped and fluid and electrolyte replacement was started. He continued 6 days later with diarrhea of 7 to 13 stools per day and a stool test for diagnosis of C. difficile infection was performed with a positive result. The patient received oral metronidazole (500 mg/t.i.d. for 10 days) and rapid improvement and eventual resolution of his diarrhea was observed after 3 days of therapy. DISCUSSION: Although no conclusive reports of this reaction exist, we think this is a case of C difficile colitis that appeared three days after valaciclovir was initiated. Colitis improved with metronidazole. Other causes of diarrhea were excluded, such as diabetes mellitus, renal failure, intestinal surgery and intestinal obstruction. Infection was confirmed by a positive test for C. difficile. The application of Naranjo's algorithm asserts the reaction as 'probable'. CONCLUSIONS: Valaciclovir-associated C. difficile colitis, although rare, can have severe consequences for the patient's health. It should be included as a possible adverse effect of valaciclovir treatment by health professionals.