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Introduction. The objective is to determine the prevalence of potentially inappropriate drugs according to the Marc, STOPP, and PRISCUS lists in elderly HIV patients. Patients and methods. It was an observational, retrospective, and multicenter study. People living with HIV 65 years or older who underwent chronic concomitant treatment were included. Descriptive and multivariate analyzes were performed to study the association between polypharmacy and potentially inappropriate medication compliance. Results. A total of 55 patients were included, 81.8% men and a median age of 69 years (IQR: 67-73). The median number of comorbidities was 3 (IQR: 2-5) and the most frequent pattern of multimorbidity was cardiometabolic (62.9%). The predominant antiretroviral treatment was triple therapy (65.5%). Polypharmacy was present in 70.9% of the patients and 25.5% had major polypharmacy. The most frequent polypharmacy pattern was cardiovascular (69.2%). The percentage of potentially inappropriate medications according to the Marc, STOPP and PRISCUS lists was 65.5%, 30.9% and 14.5%, respectively (p

Introduction: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3.& nbsp;Aims: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19.& nbsp;Results: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls.& nbsp;Conclusions: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19 & PRIME;s patients. The authors are indebted to CICDC staff for their collaborative support and dedication during the experiments. We are grateful to YJ Gonzalez ´ for her technical support, constructive discussions, and scientific input. We also thank J Delgado and SR Paez from Empresa Central de Laboratorios “Jos´e Isaac del Corral”, Havana, Cuba, for their invaluable contribution. We also thank JF Infante for the anatomopathological evaluation of hamsters. CE Rudd is supported by a grant from the Canadian Institutes of Health Research (CIHR).

Decreased antiretroviral therapy persistence is associated with increased rates of virologic failure, development of antiretroviral resistance, and increased morbidity and mortality. Different therapeutic strategies, such as single-tablet regimens (STR) and less-drug regimens (LDR), have been developed in order to simplify antiretroviral therapy (ART) and increase persistence.The primary objective was to compare antiretroviral persistence among patients receiving STRs and patients receiving LDRs. A secondary objective was to identify factors associated with non-persistence.This was a retrospective study that included treatment- experienced HIV-infected patients who received ART based on STR or LDR. Baseline patient characteristics collected included demographic information, HIV risk transmission, substance abuse during the therapy, presence of psychiatric disorder and hepatitis B or C virus infection. Kaplan-Meier analysis and Log rank was utilized to compare persistence to STR and LDR. To identify independent predictors of non-persistence we developed a multivariate Cox regression analysis.A total of 244 patients were included, 176 with STR and 68 with LDR. 60 (34.1%) patients discontinued in the STR group and 13 (19.1%) in the LDR group. The Cox regression model showed that the only variable associated with higher risk of non-persistence was the substance abuse (HR = 2.59; p = 0.005). Adverse events were the main reason for ART discontinuation in the STR group and virologic failure in the LDR group.Persistence to STR and LDR seems to be similar in pretreated HIV-infected patients. Drug abuse was the only factor identified with a higher risk of non-persistence.Objetivos: Analizar y comparar la persistencia entre las estrategias basadas en Single-Tablet Regimen (STR) y Less Drug Regimen (LDR) en pacientes VIH+. El objetivo secundario del estudio fue determinar factores predictores de persistencia. Material y métodos: Estudio observacional retrospectivo que incluyo los siguientes criterios: pacientes VIH+ con tratamiento antirretroviral (TAR) con un regimen basado en STR o LDR. Se recogieron variables demograficas, factores de riesgo de adquisicion, consumo de drogas, presencia de algun trastorno psiquiatrico y coinfeccion por el virus de la hepatitis B o C. Para comparar la persistencia entre ambas estrategias se realizo un analisis de supervivencia de Kaplan-Meir y se aplico el metodo de log-rank. Se realizo un analisis de regresion de Cox para identificar los factores predictores de persistencia. Resultados: Se incluyeron 244 pacientes, 176 con STR y 68 con LDR. El 34,1% (n = 60) de los pacientes que recibieron un regimen STR abandonaron y en el LDR el 19,1% (n = 13). Los efectos adversos fueron la principal causa de abandono del tratamiento en los pacientes que recibieron STR y el fallo virologico en el regimen LDR. La persistencia de las estrategias STR y LDR fue similar, no encontrandose diferencias estadisticamente significativas entre ambas. El consumo de drogas fue el unico factor predictivo asociado con una menor persistencia (HR = 2,59; p = 0,005). Conclusiones: La persistencia entre los regimenes STR y LDR fue similar, no detectandose diferencias significativas entre ambos. El consumo de drogas fue el unico factor independiente asociado con una menor persistencia del tratamiento antirretroviral.

To analyze the efficacy and safety of the new direct antiviral agents (DAA) that will become the new therapeutic arsenal for the treatment of hepatitis C.We carried out a research in the electronic database with the following criteria: phase II and III clinical trials (CT) published until February 2014. The Mesh term used was "chronic hepatitis C" and "therapy".Studies with boceprevir or telaprevir were excluded. For the analysis of efficacy, we evaluated the rate of Sustained Viral Response(SVR), and for the safety, side effects and safety-related discontinuations were analyzed.We included 24 CT that include associations with ribavirine(RBV) with or without peginterferon (PegINF) and associations of several DAA. The results associated of daclatasvir with PegINF and RBV have not been very successful. On the contrary, sofosbuvir presents activity in all viral genotypes . Sofosbuvir may be administered in free PegINF regimens. Around 90% of naïve patients achieve sustained virological response (RVS) and 80% in previously treated. In relation to second wave of NS3/4A protease inhibitors, simeprevir has achieved RVS in 90% of naïve patients and close to 80% in previously treated.The main combination of DAA were sofosbuvir and daclatasvir and sofosbuvir and ledipasvir. Both have achieved SVR in 100% of patients who previously had virological failure after receiving a protease inhibitor regimen with boceprevir or telaprevir.The new generation of AAD for the treatment of hepatitis C will lead to higher response rates in all subtypes of patients with lower complexity regimens and better tolerated.Objetivos: Analizar la eficacia y seguridad de los nuevos agentesantivirales directos (AAD) que formaran parte del arsenal terapéuticopara el tratamiento de la hepatitis C.Método: Se realizó una búsqueda en la base de datos electrónicaPubMed, de artículos publicados Febrero de 2014 quecumplieran los siguientes criterios: ensayos clínicos (EC) en faseII o III y cuyos objetivos fueran evaluar la eficacia y seguridad denuevas generaciones de inhibidores de la proteasa (IP) frente alVHC, excluyendo con boceprevir y telaprevir.Resultados: Se incluyeron de 24 EC que incluyen asociacionesde AAD con ribavirina (RBV) y con o sin peginterferon (PegINF)y asociaciones de varios AAD. Los resultados de daclatasvircon PegINF y RBV no han sido muy satisfactorios. Por el contrario,sofosbuvir es activo en todos los genotipos virales y permiteser administrado en regímenes libres de PegINF. Alrededordel 90% de los pacientes naïve alcanzan respuesta viralsostenida (RVS) , y no llegan al 80% en pretratados. En cuantoa la segunda generación de IP NS3/4A, destacar a simeprevir,con respuestas próximas al 90% en pacientes naïve y cercanasal 80% en pretratados. Entre las combinaciones de AAD evaluadas,sofosbuvir y daclatasvir y sofosbuvir y ledipasvir alcanzanel 100% de respuesta en no respondedores a triple terapiacon boceprevir y telaprevir.Conclusiones: Las nuevas generaciones de AAD frente al VHCvan a suponer un aumento de las tasas de curación en todoslos subtipos de pacientes, a través de regímenes más sencillosy mejor tolerados.

Background Patients with chronic hepatitis B (CHB) require long treatment in order to be able to achieve and maintain viral suppression. Therapy health outcomes are affected by how long and how the patients take their medications. Thus persistence should be defined and measured separately from adherence. For that reason we thought it would be interesting to analyse persistence on account of the limited number of studies that at present exist. Purpose To determine persistence among patients receiving nucleos (t)ide analogues (NUC) for CHB and to analyse the evolution of treatment persistence. Material and methods We conducted a retrospective study that included patients with CHB who initiated antiviral therapy and were attending the pharmaceutical care office between January 2002 and December 2011. Patients included in a clinical trial or who did not personally collect their medication were excluded. The variables were: age, gender, antiretroviral therapy (ART), reason for switch to another NUC and persistence. Patients were stratified according to the genetic barrier (GB) of the therapy (high GB therapies: tenofovir and entecavir and low GB therapies: lamivudina, adefovir and lamivudina plus adefovir). We used the Kaplan-Meier method to analyse non-persistence over the time of the study and to calculate the number of patients at risk of non-persistence each year. Results 102 patients were included. Most were men (72.5%). Average age was 45 ± 13 years. Lamivudine was prescribed in 32.4% of patients, entecavir in 24.5%, adefovir in 17.6%, tenofovir in 15.6% and lamivudine plus adefovir in 9.8%. The reasons for switching to another NUC were: breakthrough (72.7%), other (15.2%) and non-responder (12.1%). There was a statistically significant difference between low GB drugs (31.95; 95% CI 26.04 to 37.86) and high GB drugs (41.35; 95% CI 34.47 to 48.32 months). Log rank test: p = 0.008. Conclusion This study showed that high GB drugs had a better profile of persistence in the initial therapy of patients with CHB. The main reason for switching to another ART was breakthrough. These data will help in designing educational programmes, supporting pharmacist intervention to improve persistence to NUC for hepatitis B. References and/or Acknowledgements Cramer JA, Roy A, Burrell A, et al . Medication compliance and persistence: terminology and definitions. Value Health 2008;11:44-7 No conflict of interest.

Background Highly active antiretroviral therapy (HAART) has significantly reduced morbidity and mortality, transforming HIV into a chronic disease. The increase in life expectancy in these patients has led to a higher prevalence of comorbidities and use of concomitant medicines, which may limit adherence and therapeutic success. Purpose To determine the prevalence of other chronic diseases in HIV-infected patients and to identify predictors of non-adherence to HAART. Material and methods Single-centre retrospective study that included HIV-infected patients on HAART who attended pharmaceutical care at a pharmacy service from January to December 2013. The dependent variable was non-adherence to HAART (patients were considered non-adherent to HAART if the percentage of adherence through dispensing records was ≤90%). The independent variables were: sex, age, number of chronic diseases and concomitant medicines, and the presence of specific diseases (viral liver disease, dyslipidaemia, central nervous system disease, cardiovascular disease or hypertension). Statistical analysis: to identify independent predictors of non-adherence, we performed a multivariate logistic regression analysis. Results A total of 598 patients were analysed. 78.9% were men, mean age was 48 years (IQR: 42–52). The average number of comorbidities per patient was 1.6 ± 1.4. 31.3% of patients had viral liver disease, 17.9% dyslipidaemia, 15.6% central nervous system disease and 14.4% cardiovascular disease or hypertension. The average number of concurrent drugs per patient was 1.9 ± 2.7. 85.3% of patients were adherent to HAART. In the multivariate analysis, presence of viral liver disease was the only variable significantly associated with non-adherence to HAART (OR: 1.81); p = 0.02). The number of chronic diseases and concurrent drugs was not associated with non-adherence. Conclusion The prevalence of other chronic diseases in HIV-infected patients was high. The presence of viral liver disease was identified as a predictor of non-adherence in HIV-patients in this study. Reference Gleason LJ, et al. Polypharmacy in the HIV-infected older adult population. Clin Interv Aging 2013;8:749–63 No conflict of interest.

Background Imatinib has a high likelihood of drug interactions due to hepatic oxidative metabolism. Purpose To evaluate the incidence and severity of interactions between imatinib and home treatment of oncohaematology patients. Material and methods Retrospective observational study of oncohaematology patients treated with imatinib between January and March 2014. The following data were collected: age, sex, diagnosis, date of start and end of treatment with Imatinib and concomitant prescribed medicines. Imatinib interactions with other drugs were assessed by the software tool Micromedex 2.0. These were classified as: contraindicated, severe, moderate and mild. Results 24 patients were included. 58% were men (n = 14) with a mean age of 61 years. The main indication for imatinib was chronic myeloid leukaemia (54%). 164 prescriptions were analysed. The most prescribed therapeutic groups were: analgesics (19%), antidepressants and anxiolytics (16%), antihypertensives (11%) and gastric protectors (10%). 16 interactions between imatinib and concomitant treatment were detected, affecting 50% of patients. 69% were severe interactions and 31% moderate interactions. 6 patients had one severe interaction, 2 had two severe interactions, 1 patient suffered a severe and a moderate interaction and 2 patients each had two moderate interactions. Severe interactions were due to paracetamol (n = 8), acenocoumarol (n = 2) and amiodarone (n = 1). Moderate interactions were for itraconazole (n = 2), tamsulosin (n = 1), ketoconazole (n = 1) and levothyroxine (n = 1). The effect of severe interactions was reviewed and no clinical relevance was detected to date. These patients were selected for special monitoring by the pharmacist. Conclusion Like other studies on the subject, our study shows that there are numerous interactions between imatinib and other drugs. The interactions detected are severe or moderate. It is important to keep track of patients treated with imatinib who take paracetamol due to the very frequent use of this drug. Reference Farm Hosp 2014;38(4):338–363 No conflict of interest.

Background Anti-HCV treatment may add significant complexity to antiretroviral treatment (ART). The complexity of the medicines regimen could be a risk factor for non-adherence or increasing incidence of blips. Purpose To determine if the addition of anti-HCV treatment to antiretroviral treatment increases the complexity of the treatment, therefore modifying medicines adherence and incidence of blips. Materials and methods We conducted a retrospective observational study. HIV/HCV co-infected patients treated with interferon alfa-2a plus ribavirin for at least 12 weeks between 01/2008–06/2012 were included. We excluded patients with HIV viral load >50 copies RNA/mL in the six months prior to the introduction of anti-HCV treatment. The following variables were collected: sex, age, weeks on anti-HCV treatment and incidence of blips. Additionally, adherence (≥95%) and complexity index were collected before and after the addition of anti-HCV treatment. Blips were defined as a detectable HIV-RNA level (>50 copies/mL but no more than 1000 copies/mL) occurring between 2 negative assays. Complexity index was calculated based on a score (Martin et al, 2007) which considers number of pills taken per day, dosing schedule, dosage form and any specific instructions related to drug use. Quantitative and dichotomous variables were compared using the t-test for related samples and McNemar’s test respectively (confidence interval (CI) 95%). Data analysis was carried out using SPSS 20.0. Results 36 patients were included (75% male, mean age 47 ± 5). The mean duration on anti-HCV treatment was 41 ± 18 weeks. The mean value of the complexity index before and after the addition of anti-HCV treatment to ART was 5.3 ± 1.9 and 11.4 ± 1.6 respectively (p 0.005). After the introduction of the anti-HCV treatment, the number of non-adherent patients showed a non-significant increase from 11% to 22%. Conclusions The addition of anti-HCV treatment to ART correlates with a significant increase in the complexity index, leading to higher non-adherence and blips rates. No conflict of interest.

Background Pharmaceutical care consultations specialising in viral diseases seem to benefit the therapeutic objective. Purpose To analyse the frequency of changes in antiretroviral treatment regimens (ART) when the patient is able to consult a pharmacist specialising in viral diseases; to determine the causes and compare the results with available studies that do not include a consultation of this nature. Materials and methods Prospective observational study. The patients included were monoinfected HIV + and co-infected HIV/HCV patients who had been followed up in an outpatient consultation of a hospital and who had changed their ART for any reason between January 2010 and September 2013. The following variables were collected: age, sex, ART before and after the change and cause of change (adverse effects, simplification, interactions, virological failure and others). Adverse effects were classified as: gastrointestinal, renal, metabolic, hepatic, related to the central nervous system (CNS), cardiovascular and others. Data collection was done through the outpatient database and medical record reviews. Annual frequency of change and frequency depending on the cause were calculated. The data obtained were compared with those described in Davidson et al.’s study (Antiviral Research 2010, 86:227–9) concerning non-specialist consultations. Results A total of 538 ART regimens were changed, affecting 44% (n = 365) of patients. 79% were men with a mean age of 48 years. The annual rate of change was 18%. The main cause of change was adverse effects (45%) (mostly for gastrointestinal disorders (26%) and CNS disorders (21%)). This was followed by other causes (19%), simplicity (19%), virological failure (12%) and interactions (5%). Conclusions The reasons for discontinuation of ART agree in order but not in magnitude with those indicated in the existing bibliography. Fewer changes due to adverse effects were found and more changes in the hope of treatment optimisation when a specialised consultation was possible. This was due to better pharmaceutical care and better communication between doctor and pharmacist. No conflict of interest.

Background Treatment modifications during the first year of starting antiretroviral treatment (ART) are extremely important. The first ART regimen should remain for years. First regimen toxicity can have a negative impact on adherence and virological efficacy. Purpose To identify patients who discontinued treatment with antiretroviral treatment within the first year in a HIV cohort and to analyse the factors that led to discontinuation of the treatment. Materials and methods Prospective multicentre study. Treatment-naive adult HIV patients who started treatment in 2011 were selected. Basic demographic characteristics (sex and age) and the pharmacotherapeutic variables initial ART, discontinuation of ART within the first year and reasons for this based on Swiss HIV Cohort (Elzi et al . Arch Intern Med. 2010) were collected. The main reasons for treatment modification were classified as treatment failure, intolerance and/or toxic effects, the patient’s choice, the physician’s decision, and other reasons. Results 108 patients started ART in 2011, 83% men. The mean age was 40 ± 11. The most frequent ART was emtricitabine/tenofovir/efavirenz (61%) followed by emtricitabine, tenofovir, atazanavir/ritonavir (16%), emtricitabine, tenofovir, darunavir/ritonavir (12%) and other combinations (11%). During the first year of ART, 28 individuals modified their treatment. The reasons for treatment discontinuation were: 60% intolerance or toxic effects, 18% treatment failure, 14% the physician’s decision and 8% other reasons. 17 patients modified their treatment because of drug intolerance and/or drug toxicity. Gastrointestinal tract intolerance was the most frequent toxic effect (29.4%), followed by rash (23.5%), hypersensitivity (17.6%), psychiatric events (11.7%), and others (17.8%). We emphasise that 28% of patients discontinued treatment more than once in the first year, especially those in the gastrointestinal tract intolerance group. Conclusions The main reasons for treatment discontinuation were intolerance or toxic effects. It is necessary to properly assess starting ART to reduce adverse events involving changes in the treatment. No conflict of interest.

Background Antiretroviral treatment (ART) has significantly increased the life expectancy of human immunodeficiency virus (HIV)-infected individuals. However, toxicities, comorbidities and treatment failures, among others, may result in frequent ART regimen changes. Purpose To identify and analyse the ART changes and the reasons for them in HIV-infected patients over a 42-month period of study in our hospital. Materials and methods A retrospective observational study was conducted over 42 months in all outpatients on antiretroviral treatment who attended our hospital for HIV monitoring between January 2010 and June 2013. For each patient whose ART was changed we recorded the following data in a database: sex, age, previous and new treatment, reason for treatment change and resistance profile. Data was tabulated using Excel. Results During the period of study, a total of 528 patients changed ART (78% men, mean age 47 ± 7.6 years). The most common cause of change was adverse drug reactions (ADR) (47.5%). The most usual ADR were: gastrointestinal symptoms (48 patients), neuropsychiatric disorders (44 patients), renal disease (33 patients), dyslipidaemia (27 cases) and liver disease (24 cases). The drugs which caused ADR were efavirenz (8.0%), tenofovir (7.2%), atazanavir (6.3%), didanosine (6.1%) and lopinavir/ritonavir (4.4%). Other reasons for ART change were: simplification (14.6%), resistance (10.2%), treatment failure (5.5%), inclusion in a clinical trial (4.4%); and other causes (non-compliance, interactions, pregnancy, clinical decision, dose change and unknown). The most common treatment regimen before the change was tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV). After the change, tenofovir/emtricitabine (TDF/FTC) plus darunavir/ritonavir (DRV/r) was the most usual regimen. Conclusions The study revealed that a large percentage of ART changes were due to ADR. The intervention of hospital pharmacists could play an important role in the overall monitoring of HIV patients. No conflict of interest.

Background As people with HIV infections age, comorbidities and complications have increased and could affect antiretroviral therapy (ART) adherence. Purpose To determine the comorbidities of patients with HIV infection, as well as to evaluate their contribution to ART adherence. Materials and methods A twelve-month retrospective observational study (from January 2012 to December 2012) was conducted in HIV-infected patients who were being treated with ART. ART adherence was the dependent variable. We collected the following independent variables: sex, age, HCV coinfection, transmission risk, CD4 + T-cell count, HIV viral load, ART-naive, type of ART and comorbidities. We defined polypathological patients as patients with two or more chronic conditions. Adherence was determined through dispensing pharmacy records (Total number of units dispensed/Total number of units needed×100) and the simplified medicines adherence questionnaire (SMAQ). Patients who took at least 90% of their prescribed ART were classified as good adherers. We performed a univariate logistic regression to determine the relationship between the comorbidities and ART adherence. Results We included 536 patients in the study (80.2% men, mean age 47 ± 7.1 years) of whom 49.2% were HIV-HCV co-infected. Injected drug use was the main mode of HIV transmission. The median CD4 + was 574.5 cells/mm 3 (IQR: 353.8–776.3) and viral suppression ( Conclusions There is an important number of polypathological HIV-infected patients. Despite ART adherence being high, the presence of these comorbidities significantly reduces adherence. No conflict of interest.