Compassionate use of long-acting cabotegravir plus rilpivirine for people living with HIV-1 in need of parenteral antiretroviral therapy.

OBJECTIVES: Physicians could request compassionate use of oral and long-acting (LA) cabotegravir + rilpivirine for people living with HIV-1 under a single-patient request programme supported by ViiV Healthcare and Janssen. Outcomes are reported. METHODS: Eligibility criteria included need for parenteral therapy, no primary resistance mutations to cabotegravir or rilpivirine, and established retention in care. Demographic, efficacy, and safety data were obtained from standardized programme applications and quarterly clinical updates. Individuals received a loading dose of LA cabotegravir 600 mg + rilpivirine 900 mg, followed by LA maintenance doses of 400 mg/600 mg every 4 weeks; some received lead-in oral cabotegravir and rilpivirine. RESULTS: Through July 2020, 35 people living with HIV-1 had data available. The most frequent reason for compassionate use request was chronic non-adherence due to psychological conditions (n = 15). Of 35 people living with HIV-1, 28 had detectable viremia (median viral load 60 300 copies/mL) and seven were virologically suppressed at programme entry; 16/28 and 6/7 achieved or maintained virological suppression at data cutoff, respectively. Seven people living with HIV-1 discontinued for incomplete virological response, six with detectable viremia at initiation; six and four had new reverse transcriptase and integrase mutations at discontinuation, respectively. Six non-fatal serious adverse events were reported, two considered possibly treatment related. Four deaths were reported; none were treatment related. One individual reported two pregnancies and continued LA dosing. CONCLUSIONS: Most people living with HIV-1 had advanced disease and achieved (16/28) or maintained (6/7) virological suppression with LA therapy. Cabotegravir LA + rilpivirine LA as compassionate use provided a valuable treatment option for individuals with adherence issues with oral therapy and advanced disease.

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.