A Risk Assessment Tool for Predicting Fragility Fractures in People with HIV: Derivation and Internal Validation of the FRESIA Model.

People with HIV have a higher risk of fracture than the general population. Because of the low performance of the existing prediction tools, there is controversy surrounding fracture risk estimation in this population. The aim of the study was to develop a model for predicting the long-term risk of fragility fractures in people with HIV. We included 11,899 individuals aged ≥30 years from the Spanish HIV/AIDS research network cohort. We identified incident fragility fractures from medical records, defined as nontraumatic or those occurring after a casual fall, at major osteoporotic sites (hip, clinical spine, forearm, proximal humerus). Our model accounted for the competing risk of death and included 12 candidate predictors to estimate the time to first fragility fracture. We assessed the discrimination and calibration of the model and compared it with the FRAX tool. The incidence rate of fragility fractures was 4.34 (95% CI 3.61 to 5.22) per 1000 person-years. The final prediction model included age, chronic kidney disease, and chronic obstructive pulmonary disease as significant predictors. The model accurately predicted the 5- and 10-year risk of fragility fractures, with an area under the receiving operator characteristic curve of 0.768 (95% CI 0.722 to 0.814) and agreement between the observed and expected probabilities. Furthermore, it demonstrated better discrimination and calibration than the FRAX tool, improving the classification of over 35% of individuals with fragility fractures compared to FRAX. Our prediction model demonstrated accuracy in predicting the long-term risk of fragility fractures. It can assist in making personalized intervention decisions for individuals with HIV and could potentially replace the current tools recommended for fracture risk assessment in this population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Organisational and financial consequences of the early discharge of patients treated for acute bacterial skin and skin structure infection and osteomyelitis in infectious disease departments in Greece, Italy and Spain: a scenario analysis.

OBJECTIVE: The aim of the analysis is to assess the organisational and economic consequences of adopting an early discharge strategy for the treatment of acute bacterial skin and skin structure infection (ABSSSI) and osteomyelitis within infectious disease departments. SETTING: Infectious disease departments in Greece, Italy and Spain. PARTICIPANTS: No patients were involved in the analysis performed. INTERVENTIONS: An analytic framework was developed to consider two alternative scenarios: standard hospitalisation care or an early discharge strategy for patients hospitalised due to ABSSSI and osteomyelitis, from the perspective of the National Health Services of Greece, Italy and Spain. The variables considered were: the number of annual hospitalisations eligible for early discharge, the antibiotic treatments considered (ie, oral antibiotics and intravenous long-acting antibiotics), diagnosis-related group (DRG) reimbursements, number of days of hospitalisation, incidence and costs of hospital-acquired infections, additional follow-up visits and intravenous administrations. Data were based on published literature and expert opinions. PRIMARY AND SECONDARY OUTCOME MEASURES: Number of days of hospitalisation avoided and direct medical costs avoided. RESULTS: The total number of days of hospitalisation avoided on a yearly basis would be between 2216 and 5595 in Greece (-8/-21 hospital beds), between 15 848 and 38 444 in Italy (-57/-135 hospital beds) and between 7529 and 23 520 in Spain (-27/-85 hospital beds). From an economic perspective, the impact of the early discharge scenario is a reduction between €45 036 and €149 552 in Greece, a reduction between €182 132 and €437 990 in Italy and a reduction between €292 284 and €884 035 in Spain. CONCLUSIONS: The early discharge strategy presented would have a positive organisational impact on National Health Services, leading to potential savings in beds, and to a reduction of hospital-acquired infections and costs.

Healthcare and economic impact. / Atención sanitaria e impacto económico.

This chapter reviews the current model of HIV patient care and its economic impact. There are clinical and geographical differences in the care HIV patients receive and a need to develop new models of comprehen-sive HIV care has been identified. HIV infection in Spain is an important and expensive public health problem. The main costs are due to an-tiretroviral therapy, indirect costs and the cost of admission, consultation and diagnostic testing. A strong correlation between severity and cost has been identified. Patients diagnosed late have a poorer clinical course, increased mortality and require more medical and therapeutic resources. Early detection of the disease significantly improves the clinical outcomes of patients. The increased number of patients receiving treatment and their progressive ageing will increase costs of HIV healthcare in the coming years.

Cost-utility analysis of the fixed-dose combination of dolutegravir/abacavir/lamivudine as initial treatment of HIV+ patients in Spain.

OBJECTIVE: Fixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients. The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC) versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and darunavir/r (DRV/r) or raltegravir (RAL) with emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. METHOD: The ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and the fixed- dose combinations of emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) with darunavir/r (DRV/r) or raltegravir (RAL). The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015). The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. RESULTS: Treatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY), vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY), and vs. RAL + FTC/TDF or ABC/3TC (-1 005 117.13€/QALY). All the sensitivity analyses performed showed the consistency of these findings. CONCLUSIONS: With the premises considered, treatment initiation with DTG/ABC/3TC STR appears to be the most cost-effective option in ARTnaïve HIV infected patients from the Spanish Health System perspective.

Objetivo: Las combinaciones a dosis fijas de medicamentos antirretrovirales han significado un importante paso adelante en la simplificación del tratamiento y la mejora del cumplimiento, así como hacia una mayor eficacia de la terapia, una disminución de la carga viral y una mejora de la calidad de vida de los pacientes. La formulación de un comprimido único una vez al día con dosis fijas de dolutegravir, abacavir y lamivudina (DTG/ABC/3TC) para pacientes infectados con VIH es un régimen altamente eficaz y bien tolerado. El objetivo del estudio fue evaluar la relación coste- utilidad incremental de la combinación de dosis fija de (DTG/ABC/3TC) versus las combinaciones de emtricitabina/tenofovir/efavirenz (TDF/FTC/EFV) y darunavir/r (DRV/r) o raltegravir (RAL) con emtricitabina/tenofovir (FTC/TDF) o abacavir/lamivudina (ABC/3TC) como tratamiento antirretroviral inicial en pacientes infectados con VIH-1 desde la perspectiva del Sistema Nacional de Salud Español.Método: Se adaptó en España el modelo ARAMIS. Este utiliza un enfoque de microsimulación para emular los cambios individuales en cada paciente desde el inicio del tratamiento hasta su muerte mediante una cadena de Markov de estados de salud descriptivos de la enfermedad. Las alternativas empleadas para la comparación fueron la combinación de dosis fijas de emtricitabina/tenofovir/efavirenz (TDF/FTC/EFV) y las combinaciones de dosis fijas de emtricitabina/tenofovir (FTC/TDF) o abacavir/lamivudina (ABC/3TC) con darunavir/r (DRV/r) o raltegravir (RAL). La probabilidad de lograr la supresión virológica mediante los tratamientos incluidos en el modelo se ha obtenido de ensayos clínicos individuales, SPRING2 y FLAMINGO, y los costes fueron expresados en € (2015). El uso del modelo de la perspectiva del Sistema Nacional de Salud español, con un horizonte de vida útil y una tasa de descuento del 3% se, aplicó a coste y efectividad.Resultados: El inicio de tratamiento con DTG/ABC/3TC fue dominante cuando se comparó con el inicio del tratamiento con el resto de comparadores: frente a TDF/FTC/EFV (-67.210,710 € / AVAC) vs DRV/r FTC/TDF o ABC/3TC (-1,787,341.44 € / AVAC) y vs RAL FTC/TDF o ABC/3TC (-1,005,117.13 € / AVAC). Todos los análisis de sensibilidad realizados demostraron la consistencia de estos hallazgos.Conclusiones: Con las premisas consideradas, el inicio del tratamiento con la combinación a dosis fijas de DTG/ABC/3TC parece ser la opción más rentable para el tratamiento de pacientes infectados con el VIH desde la perspectiva del Sistema Nacional de Salud español.

Pre-exposure prophylaxis (PrEP) against HIV: efficacy, safety and uncertainties.

Despite the global stabilization of the number of new HIV infections in recent years, there has been an increase in new infections among men who have sex with men. This fact indicates the lack of effectiveness of the measures and prevention campaigns established so far for this group.  It is therefore necessary to implement alternative preventive measures for them. Pre-exposure pharmacological prophylaxis (PrEP) is one of the best evaluated options and has had high protection rates in both clinical and real-life trials. The strategy has also shown an adequate profile in terms of safety, tolerance, adverse effects and cost-effectiveness in the studies carried out to assess this important topic.

En los últimos años se ha objetivado un incremento de las nuevas infecciones por el VIH en el grupo de hombres que tienen sexo con hombres, lo que indica la ausencia de eficacia de las campañas y medidas preventivas instauradas en dicho grupo.Es necesario, por tanto, implementar medidas preventivas alternativas, siendo la profilaxis farmacológica pre-exposición (PrEP) una de las opciones mejor evaluadas tanto en ensayos clínicos como en la vida real, habiéndose demostrado tasas de protección superiores al 80% cuando se administra en los casos indicados y con buen cumplimiento terapeútico.La estrategia ha demostrado, además, un perfil adecuado en seguridad,tolerancia y efectos adversos, siendo además coste-efectiva según losestudios realizados para valorar este importante aspecto.

[Cost of nucleoside analogue reverse transcriptase inhibitor-related toxicity in HIV-1-infected patients]. / Costes de la toxicidad asociada a los análogos de nucleósidos inhibidores de la transcriptasa inversa en pacientes con infección por el VIH-1.

OBJECTIVE: To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV-1-infected patients. METHODS: . A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians. RESULTS: The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 euro, which included 1789 euro in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 euro in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 euro), lipodystropy (535 euro) and peripheral neuropathy (533 euro). CONCLUSION: Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies.