Original article
Cost–effectiveness of initial antiretroviral treatment administered as single vs. multiple tablet regimens with the same or different componentsCoste-efectividad del tratamiento inicial antirretroviral de comprimido único vs. tratamiento con regímenes de múltiples comprimidos con los mismos o diferentes componentes

https://doi.org/10.1016/j.eimc.2016.07.006Get rights and content

Abstract

Objective

To evaluate the efficiency of single-tablet regimens (STR) and multiple-tablet regimens (MTR) with exactly the same or different components.

Methods

A study was conducted on HIV-1-infected antiretroviral-naïve patients from 6 Spanish or French centers, who were started on treatment with STR-Atripla®, or the same components separately (MTR-SC), or a different MTR (MTR-Other). Effectiveness was measured as percentage of HIV-RNA <50 copies/mL at 48 weeks (ITT). Efficiency was the ratio between costs (direct cost of antiretrovirals plus outpatient visits, hospital admissions, and resistance tests) and effectiveness.

Results

The study included a total of 2773 patients (759 STR-Atripla®, 483 MTR-SC, and 1531 MTR-Other). Median age was 37 years, 15% were HCV co-infected, 27% had a CD4+ count <200 cells/μL, and 30% had viral load ≥100.000 copies/mL. The duration of the assigned treatment was longer for STR-Atripla® (P < .0001). Response rates (adjusted for CD4+ count, viral load, and clustered on hospitals) at 48 weeks were 76%, 74%, and 62%, respectively (P < .0001). Virological failure was more common in MTR patients (P = .0025), and interruptions due to intolerance with MTR-Other (P < .0001). Cost per responder at 48 weeks (efficiency) was €12,406 with STR-Atripla®, €11,034 with MTR-SC (0.89 [0.82, 0.99] times lower), and €18,353 (1.48 [1.38, 1.61] times higher) with MTR-Other.

Conclusions

STR-Atripla® and MTR-SC regimens showed similar effectiveness, but virological failure rate was lower with STR-Atripla. MTR-SC, considered less convenient, had a marginally better efficiency, mainly due to lower direct costs. MTR-Other regimens had both a worse effectiveness and efficiency. Similar efficiency analyses adjusting for baseline characteristics should be recommended for new STRs.

Resumen

Objetivo

Evaluar la eficiencia de un régimen antirretroviral de comprimido único diario (STR) y de regímenes de múltiples comprimidos (MTR) con exactamente los mismos (MTR-SC) o distintos componentes (MTR-Other).

Métodos

Se incluyeron pacientes con infección por VIH-1 no tratados de 6 centros españoles o franceses que iniciaron tratamiento con STR-Atripla®, MTR-SC, o MTR-Other. La eficacia se midió como el porcentaje de VIH-ARN < 50 copias/ml (48 semanas, ITT). La eficiencia fue el cociente entre los costes (costes directos de los antirretrovirales, visitas ambulatorias, ingresos y estudios de resistencia) y la eficacia.

Resultados

Fueron incluidos 2.773 pacientes (759 STR-Atripla®, 483 MTR-SC, 1.531 MTR-Other) con una edad media de 37 años, el 15% coinfectados por VHC, el 27% con CD4+ < 200 células/μl y el 30% con carga viral ≥ 100.000 copias/ml. La duración del tratamiento asignado fue mayor para STR-Atripla® (p < 0,0001). La respuesta (ajustada para CD4+, carga viral y centro hospitalario) a 48 semanas fue del 76, 74 y 62%, respectivamente (p < 0,0001). El fracaso virológico fue más frecuente con ambos MTR (p = 0,0025), y las interrupciones por intolerancia lo fueron con MTR-Other (p < 0,0001). El coste por respondedor a 48 semanas (eficiencia) fue 12.406 € con STR-Atripla®, 11.034 € con MTR-SC (0,89 [0,82-0,99] veces menor), y 18.353 € (1,48 [1,38-1,61] veces mayor) con MTR-Other.

Conclusiones

STR-Atripla® y MTR-SC mostraron una eficacia similar, pero con menor fracaso virológico con STR-Atripla. MTR-SC, considerado menos conveniente, tuvo una eficiencia marginalmente mayor, principalmente debido a menores costes directos. MTR-Other tuvo una eficacia y eficiencia peores. Deberían recomendarse estudios similares con otros nuevos STR ajustados a las características basales de los pacientes.

Introduction

Fixed-dose single tablet regimens (STR) are generally preferred by patients and physicians. As long as they include drugs of choice, co-formulated drugs are specifically recommended by antiretroviral treatment (ART) guidelines, unless dose-adjustments are required.1, 2, 3, 4 They represent a significant advance in the simplification of ART, facilitating adherence to complex and chronic treatments, and contributing to a quantifiable improvement in patient's quality of life.5 STRs reduce the risk of treatment error, are associated with lower risks of hospitalization, can lessen the possibility of covert monotherapy if selective noncompliance, reduce the risk of developing HIV-1 resistance, and can impact treatment costs as well.6, 7, 8, 9, 10, 11, 12, 13 One study found that STR led to a 17% reduction in overall healthcare costs.7 However, most of these studies have baseline prescription bias and no randomized clinical trials using drugs as they are prescribed in an unblinded way have demonstrated these potential benefits of STR so far. Moreover, efficiency of STR has never been compared with a MTR with same components.

We hypothesized that despite having a possible higher direct cost, the efficiency (cost–effectiveness) of STR might be better when compared with a multi-tablet regimen (MTR) with the same or different components in antiretroviral-naïve subjects.

Section snippets

Methods

This was an observational open clinical study undertaken in a prospectively collected cohort data. All antiretroviral naïve HIV-infected patients from 6 reference centers (4 from Barcelona, Spain; 1 from Madrid, Spain; 1 from Paris, France) who initiated ART with the STR-Atripla®, with their exact components administered separately (Tenofovir disoproxil fumarate [DF] + Lamivudine/Emtricitabine + Efavirenz, or with Truvada® + Efavirenz; MTR-SC) or with a MTR with different components (MTR-Other)

Baseline characteristics

A total of 2773 patients (759 (27%) STR-Atripla®, 483 (17%) MTR-SC, and 1531 (55%) MTR-Other) were included. There were significant differences among centers and between Spanish and French centers in the type of regimens prescribed, suggesting differences in local practices for ART prescription. Baseline characteristics are illustrated in the Supplemental Table 1. The most commonly prescribed MTR-Other regimens are listed in the Supplemental Table 2. The STR-Atripla® arm had a significantly

Discussion

In this prospective multicenter study we did not found significant differences in the 48-week response rates, the median duration of assigned regimen, the rates of patients completing at least one year of follow-up, and the rates of interruptions for tolerance problems among subjects receiving their initial ART as STR-Atripla® or MTR-SC. However, the rates of virological failure were significantly lower with STR-Atripla®. The cost per responder (efficiency) at 48 weeks was lower for MTR-SC

Funding

Supported in part by an unrestricted grant from Gilead Sciences.

Conflicts of interest

Josep M. Llibre has been a member of the speakers’ bureaus and received fees from lectures or for participating in advisory boards from Janssen-Cilag, Merck Sharp & Dohme, ViiV Healthcare, Gilead Sciences and Bristol Myers Squibb.

Arkaitz Imaz has received financial compensation for lectures, consultancies, or educational activities from Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dome, and ViiV Healthcare.

Daniel Podzamczer has received research grants and/or honoraria

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