Patterns of Sexualized Drug Use among Gay, Bisexual, and Other Men Who Have Sex with Men Living with HIV: Insights from a Comprehensive Study-The U-SEX-2 GESIDA 9416 Study.

BACKGROUND: Sexualized drug use (SDU) has become a public health concern in recent years. This study aimed to estimate the prevalence of SDU in gay, bisexual, and other men who have sex with men living with HIV (HIV + GBMSM) in Madrid during 2019/2020 and compare it with data from 2016/2017 in order to detect changes in patterns. METHODS: We analyzed the frequency of SDU in a sample of HIV + GBMSM attending HIV clinics, who participated in an anonymous online survey regarding sexual behavior and recreational drug use. The association between SDU, sexual risk behaviors, and STIs was evaluated. RESULTS: This study included 424 HIV + GBMSM, with a mean age of 40 (10.43) years. Overall, 94% (396) reported being sexually active. Additionally, 33% (140) had been diagnosed with an STI within the previous year. Moreover, 54% (229) had used drugs in the last year, 25% (107) engaged in SDU, and 16% (17) reported engagement in slamsex. After adjusting for confounding factors, SDU was associated with STIs, fisting, unprotected anal intercourse, and having >24 sexual partners in the last year. According to the DUDIT test scores, 80% (81) probably had problematic drug use (≥6 points), and 8% (8) probable drug dependence (≥25 points). When comparing the U-SEX-1 (2016/2017) data with the U-SEX-2 (2019/2020) data, no significant differences were found in the proportion of participants practicing SDU or slamming. CONCLUSIONS: The prevalence of SDU among HIV + GBMSM has remained high in recent years and without significant changes. The risk of problematic drug use among those who practice SDU is high. We observed a clear association between SDU, high-risk sexual behaviors, and STIs.

HIV medical care interruption among people living with HIV in Spain, 2004-2020.

OBJECTIVE: We estimated the incidence rate of HIV medical care interruption (MCI) and its evolution over a 16-year-period, and identified associated risk factors among HIV-positive individuals from the Cohort of the Spanish AIDS Research Network in 2004-2020. DESIGN: We included antiretroviral-naive individuals aged at least 18 years at enrolment, recruited between January 1, 2004, and August 30, 2019, and followed-up until November 30, 2020. METHODS: Individuals with any time interval of at least 15 months between two visits were defined as having a MCI. We calculated the incidence rate (IR) of having at least one MCI and used multivariable Poisson regression models to identify associated risk factors. RESULTS: Of 15 274 individuals, 5481 (35.9%) had at least one MCI. Of those, 2536 (46.3%) returned to HIV care after MCI and 3753 (68.5%) were lost to follow-up at the end of the study period. The incidence rate (IR) of MCI was 7.2/100 person-years (py) [95% confidence interval (CI): 7.0-7.4]. The annual IR gradually decreased from 20.5/100 py (95% CI: 16.4-25.6) in 2004 to 4.9/100 py (95% CI: 4.4-5.5) in 2014, a slight increase was observed between 2015 and 2018, reaching 9.3/100 py (95% CI: 8.6-10.2) in 2019. Risk factors for MCI included younger age, lower educational level, having contracted HIV infection through injecting drug use or heterosexual intercourse, having been born outside of Spain, and CD4 + cell count >200 cell/µl, viral load <100 000 and co-infection with hepatitis C virus at enrolment. CONCLUSIONS: Around a third of individuals had at least one MCI during the follow-up. Identified predictors of MCI can help health workers to target and support most vulnerable individuals.

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial.

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53-74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4-13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12-45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D3 for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.

Amikacin pharmacokinetics in elderly patients with severe infections.

OBJECTIVE: The aim of this study was to characterize the population pharmacokinetics of amikacin in elderly patients by means of nonlinear mixed effects modelling and to propose initial dosing schemes to optimize therapy based on PK/PD targets. METHOD: A total of 137 elderly patients from 65 to 94 years receiving intravenous amikacin and routine therapeutic drug monitoring at Hospital Universitario Severo Ochoa were included. Concentration-time data and clinical information were retrospectively collected; initial doses of amikacin ranged from 5.7 to 22.5 mg/kg/day and each patient provided between 1 and 10 samples. RESULTS: Amikacin pharmacokinetics were best described by a two-compartment open model; creatinine clearance (CrCL) was related to drug clearance (2.75 L/h/80 mL/min) and it was augmented 28% when non-steroidal anti-inflammatory drugs were concomitantly administered. Body mass index (BMI) influenced the central volume of distribution (17.4 L/25 kg/m2). Relative absolute prediction error was reduced from 33.2% (base model) to 17.9% (final model) when predictive performance was evaluated with a different group of elderly patients. A nomogram for initial amikacin dosage was developed and evaluated based on stochastic simulations considering final model to achieve PK/PD targets (Cmax/MIC>10 and AUC/MIC>75) and to avoid toxic threshold (Cmin<2.5 mg/L). CONCLUSION: Initial dosing approach for amikacin was designed for elderly patients based on nonlinear mixed effects modeling to maximize the probability to attain efficacy and safety targets considering individual BMI and CrCL.

Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D.

Main cause of severe illness and death in COVID-19 patients appears to be an excessive but ineffectual inflammatory immune response that may cause severe acute respiratory distress syndrome (ARDS). Vitamin D may favour an anti-inflammatory environment and improve cytotoxic response against some infectious diseases. A multicenter, single-blind, prospective, randomized clinical trial was approved in patients with COVID-19 pneumonia and levels of 25-hydroxyvitamin D (25(OH)D) of 14.8 ng/ml (SD: 6.18) to test antiviral efficacy, tolerance and safety of 10,000 IU/day of cholecalciferol (vitamin D3) for 14 days, in comparison with 2000 IU/day. After supplementation, mean serum 25(OH)D levels increased to 19 ng/ml on average in 2000 IU/day versus 29 ng/ml in 10,000 IU/day group (p < 0.0001). Although levels of inflammatory cytokines were not modified by treatment with 10,000 IU/day, there was an increase of anti-inflammatory cytokine IL-10 and higher levels of CD4+ T cells, with predominance of T central memory subpopulation. Cytotoxic response against pseudotyped SARS-CoV-2 infected cells was increased more than 4-fold in patients who received 10,000 IU/day. Moreover, levels of IFNγ were significantly higher in this group. Beneficial effect of supplementation with 10,000 IU/day was also observed in participants who developed ARDS and stayed at the hospital for 8.0 days, whereas those who received 2000 IU/day stayed for 29.2 days (p = 0.0381). Administration of high doses of vitamin D3 as adjuvant of the standard care treatment during hospitalization for COVID-19 may improve the inflammatory environment and cytotoxic response against pseudotyped SARS-CoV-2 infected cells, shortening the hospital stay and, possibly, improving the prognosis.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

OBJECTIVES: To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. METHODS: We included adults aged > 18 years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥ 50 copies/mL at week 48 and pVL ≥ 200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. RESULTS: Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA > 5 log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95% CI: 1.9-15.1), even in participants treated with INSTIs. CONCLUSIONS: The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA > 5 log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

Late HIV diagnosis among immigrants in Spain vs. native-born Spaniards, 2010-15.

BACKGROUND: In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards. METHODS: Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates. RESULTS: The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P < 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immigrants vs. native-born Spaniards was 1.15 [95% confidence interval (CI), 1.02-1.28], after adjusting for covariates. This disparity widened from 2010 to 2011 (APR = 1.14, 95% CI, 1.02-1.29) to 2012-15 (APR = 1.28, 95% CI, 1.17-1.39), although the change was not statistically significant. CONCLUSIONS: Immigrants in Spain had a higher risk of LHD compared with native-born counterparts. LHD is an important healthcare marker due to the positive benefits of early HIV diagnosis, including prevention, improvements in health outcomes and decreases in overall cost of treatment. More research is needed on the causes of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.

Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity.

Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.

Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy.

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size.

Mortality in Perinatally HIV-infected Adolescents After Transition to Adult Care in Spain.

INTRODUCTION: After the introduction of combination antiretroviral treatment, (ART) mortality in HIV-infected patients has dramatically decreased. However, it is still high in patients at risk, as adolescents transitioning to adult care (AC) without virologic control. The aim of this study was to characterize mortality and comorbidities of perinatally infected HIV (PHIV) patients after transition to AC. METHODS: A multicenter retrospective study from patients included in the CoRISpe-FARO Spanish cohort was conducted. PHIV patients who died after transition to AC between 2009 and 2019 were included. Clinical, immunovirologic characteristics, treatments received, comorbidities and causes of death were described. RESULTS: Among 401 PHIV patients, 14 died (3.5%). All were Spanish, 11/14 (78.6%) women. The median age at diagnosis was 1.5 years (interquartile range [IQR] 0.5-3.9), at transfer to AC was 18 years [16.1-19.9] and at death was 25.8 years [23.6-27.1]. In pediatric units [pediatric care (PC)], CD4+ nadir was 85 cells/µL [IQR 9.7-248.5] and 6/14 patients were classified as C-clinical stage. During AC, all patients were on C-clinical stage and CD4+ nadir dropped to 11.5 cells/µL [4.5-43.3]. cART adherence was extremely poor: in PC, 8/14 patients registered voluntary treatment interruptions; only one had undetectable VL at transition. In AC, 12/14 patients stopped treatment 2 or more periods of time. All deaths were related to advanced HIV disease. Mental health disorders were observed in 7/14 (50%). Main complications described: recurrent bacterial infections (57.1%), wasting syndrome (42.9%), esophageal candidiasis (28.6%) and Pneumocystis jirovecii pneumonia (28.6%). Four women had 11 pregnancies; 5 children were born (none infected). CONCLUSIONS: Young adults PHIV infected who transition to AC without virologic suppression or proven ability to adhere to ART are at high risk of mortality. Mortality was noted as a consequence of advanced HIV disease, frequent mental health problems and poor adherence to ART.

Efficacy of an information system addressed to nursing staff for diminishing contaminated blood cultures: a blind clinical trial / Eficacia de un sistema de información dirigido al personal de enfermería para disminuir la contaminación de los hemocultivos: un ensayo clínico ciego

Introduction: Evaluate the efficacy of an information system addressed to nursing staff to lower the blood culture contamination rate. Methods: A blind clinical trial was conducted at Internal Medicine and Emergency Departments during 2011. After following a reeducation program in BC extraction, participants were randomly selected in a 1:1 ratio. Every participant of the experimental group was informed of each worker's individual performance; whereas the control group was only informed of the global results. Results: A total of 977 blood extractions were performed in 12 months. Blood culture contamination rate was 7.5%. This rate was higher in the Emergency Department than in Internal Medicine (10% vs. 3.8%; p=0.001). Factors associated with the higher risk of contamination were, in the univariate analysis, the extraction through a recently implanted blood route and the time of professional experience, while those associated with a lower risk were the extraction in Internal Medicine and through a butterfly needle. On multivariate analysis, extraction through a recently placed access was an independent risk factor for an increased contamination rate (OR 2.29; 95%CI 1.18-4.44, p=0.014), while individual information about the blood culture results (OR 0.11; 95%CI 0.023-0.57; p=0.008), and more than 9 years of professional experience were asso-ciated with fewer contaminations (OR 0.30; 95%CI 0.12-0.77; p=0.012). In the intervention group the contamination rate diminished by a 26 %. Conclusions: Drawing blood cultures through a recently taken peripheral venous access increased their risk of contamination. The intervention informing the nurse staff of the contamination rate is effective to decrease it

Objetivos: Evaluar la eficacia de un sistema de información dirigido al personal de enfermería, en la reducción de la tasa de contaminación de los hemocultivos. Métodos: Durante el año 2011, se realizó un ensayo clínico en los servicios de Medicina Interna y de Urgencias. Después de seguir un programa de reeducación en la extracción de los hemocultivos, los participantes, fueron aleatorizados en una proporción de 1:1. En el grupo de intervención se informó del porcentaje de hemocultivos contaminados de cada profesional y en el grupo control se aportaba la información del porcentaje global de contaminaciones. Resultados: Durante un periodo de 12 meses se realizaron 977 extracciones. La tasa de contaminación de los hemocultivos fue del 7,5%. Esta tasa fue mayor en Urgencias que en Medicina Interna (10% versus 3,8%, p=0,001). Los factores asociados con mayor riesgo de contaminación fueron, en el análisis univariable: la extracción a través de una vía sanguínea recientemente implantada y el tiempo de experiencia profesional; mientras que los que se asociaron con menor riesgo fueron la extracción en Medicina Interna (versus en Urgencias) y a través de una palomilla. En el análisis multivariable, la extracción de los hemocultivos de una vía recientemente implantada se relacionó de forma independiente con un incremento de las contaminaciones (OR 2,29, IC 95% 1,18-4,44, p=0,014),mientras que la información individual sobre los resultados de los hemocultivos (OR 0.11; IC 95% 0,023-0,57; p=0,008) y la experiencia profesional mayor de 9 años, lo hizo con menos contaminaciones (OR 0,30, IC 95% 0,12-0,77, p=0,012). En el grupo de intervención la tasa de contaminaciones se redujo en un 26%. Conclusión: La extracción de hemocultivos a través de una vena periférica recientemente implantada aumentó el riesgo de contaminación de los mismos. La intervención informativa a los enfermeros de la tasa de contaminación de los hemocultivos, es eficaz para disminuirla

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study.

BACKGROUND: Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN: Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS: We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. RESULTS: The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/µL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9-24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. CONCLUSIONS: Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

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.

Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

BACKGROUND: Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for maintenance of human immunodeficiency virus type 1 (HIV-1) suppression. METHODS: This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine) and with no resistance were randomized to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129). The primary endpoint was the proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the snapshot algorithm. RESULTS: A total of 249 participants received study drugs (intention-to-treat exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively. CONCLUSIONS: Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. CLINICAL TRIALS REGISTRATION: NCT02159599.

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 / Predictive factors of clinically significant drug-drug interactions among regimens based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors and raltegravir

Fundamento y objetivo: Determinar la prevalencia y los tipos de interacciones farmacológicas clínicamente significativas (IFCS) en los regímenes farmacológicos de los pacientes infectados por VIH que están recibiendo un tratamiento antirretroviral, y desarrollar una herramienta diagnóstica que pueda predecir la posibilidad de una IFCS. Material y métodos: Diseño: revisión retrospectiva de bases de datos. Centro: Hospital Universitario Severo Ochoa, Unidad de Infecciosas. Participantes: 142 participantes seguidos por uno de los autores fueron seleccionados desde enero de 1985 hasta diciembre de 2014. Recogida de datos: recogimos en la última visita disponible de los participantes información relacionada con la infección VIH, las comorbilidades, los datos demográficos y los fármacos que estuvieran recibiendo, tanto los antirretrovirales como aquellos no relacionados con la infección VIH. Se definió la existencia de IFCS por la información de la ficha técnica y/o la base de datos de interacciones de fármacos antirretrovirales de la Universidad de Liverpool (http://www.hiv-druginteractions.org). Mediante el modelo de análisis multivariable de regresión logística y con la estimación de la curva de rendimiento diagnóstico obtenida identificamos una herramienta que nos pudiera predecir la existencia de interacciones farmacológicas. Resultados: De 142 pacientes, 39 (29,11%) tenían algún tipo de IFCS y en 11,2% se detectaron 2 o mas interacciones. Solo en un paciente la combinación de los fármacos estaba contraindicada (este paciente estaba recibiendo darunavir/r y quetiapina). En el análisis multivariable, los factores predictores de IFCS fueron el que estuvieran recibiendo un régimen basado en IP o ITINAN y la presencia de 3 o más fármacos no antirretrovirales (AUC 0,886, IC 95% 0,828-0,944; p = 0,0001). El riesgo fue 18,55 veces en aquellos que recibían ITINAN y 27,95 veces en los que recibían IP con respecto a aquellos que tomaban raltegravir. Conclusiones: Las interacciones farmacológicas, incluyendo aquellas definidas como clínicamente significativas, son frecuentes en pacientes infectados por VIH tratados con antirretrovirales, y este riesgo es mayor en los regímenes basados en IP. Prescribiendo regímenes basados en raltegravir, especialmente en pacientes que reciben al menos 3 fármacos no relacionados con el VIH, se podrían evitar interacciones (AU)

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. Material and methods: 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 (AU)

[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.

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 / 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

Fundamentos y objetivo. La inversión del cociente CD4/CD8 como indicador de inmunosenescencia puede ser un factor que permita anunciar el riesgo de presentar comorbilidades. Estudiamos la influencia del envejecimiento y de la inversión del cociente CD4/CD8 en la incidencia de comorbilidades y de mortalidad en la cohorte del Hospital Severo Ochoa. Métodos: Analizamos las diferencias en las tasas de incidencia de las comorbilidades ajustadas por la edad y evaluamos la inversión del cociente CD4/CD8 como factor de riesgo para la mortalidad y para el desarrollo de comorbilidades. Resultados: La edad se asoció a un incremento en la tasa de incidencia de diabetes mellitus, fracturas, EPOC y neoplasias no asociadas a sida. Encontramos un mayor riesgo de la tasa de incidencia de episodios clínicos no asociados a sida (OR 2,25; IC 95% 1,025-4,94) y episodios asociados a sida (OR 3,48; IC 95% 1,58-7,64) en los individuos con el cociente CD4/CD8 < 0,7. También los pacientes con un cociente CD4/CD8 < 0,7 presentaron una mayor riesgo de mortalidad (OR 5,96; IC 95% 0,73-48,40). Conclusión: Es importante detectar y prevenir comorbilidades no asociadas a sida en presencia del cociente CD4/CD8 < 0,7 (AU)

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 (AU)

[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.