Cost-Utility Analysis of a Dolutegravir-Based Versus Low-Dose Efavirenz-Based Regimen for the Initial Treatment of HIV-Infected Patients in Cameroon (NAMSAL ANRS 12313 Trial)

Abstract

Objectives: Evidence comparing the economic and patient values of the World Health Organization's preferred (dolutegravir 50 mg [DTG]-based) and alternative (low-dose [400 mg] efavirenz [EFV400]-based) first-line antiretroviral regimens is limited. We compared patient-reported outcomes (PROs), costs, and the cost-utility of DTG- versus EFV400-based regimens in treatment-naive HIV-1 adults in the randomised NAMSAL ANRS 12313 trial in Yaoundé, Cameroon.

Methods: We used clinical data, PROs, and health resource use data collected in the trial's first 96 weeks (2016-2019). Quality-adjusted life-years (QALYs) were computed using utility scores obtained from the 12-item Short Form (SF-12) generic health scale. Other PROs included perceived symptoms, depression, anxiety, and stress. In the 96-week base-case analysis, we estimated the unadjusted and multivariate-adjusted (1) mean costs (in US$, 2016 values) and QALYs/patient, (2) incremental costs and QALYs/patient, and (3) net health benefit (NHB). Outcomes were extrapolated over 5 and 10 years. Uncertainty was assessed using the cost-effectiveness acceptability curve and scenario and cost-effective price threshold analyses.

Results: In the base-case analysis, the NHB (95% confidence interval) for the DTG-based regimen relative to the EFV400-based regimen was 0.056 (- 0.037 to 0.153), corresponding to an 88% probability of DTG being cost-effective. A 10% decrease in this regimen's price (from $5.2 to $4.7/month) would increase its cost-effectiveness probability to 95%. When extrapolating outcomes over 5 and 10 years, the DTG-based regimen had a 100% probability of being cost-effective for a large range of cost-effectiveness thresholds.

Conclusions: At 2020 antiretroviral drug prices, a DTG-based first-line regimen should be preferred over an EFV400-based regimen in sub-Saharan Africa.

Trial registration: ClinicalTrials.gov Identifier: NCT02777229.

Fig. 1

State transition diagram for the Markov cohort simulation model. The oval boxes represent the different HSs in the model. Arrows denote the transitions between HSs according to immunological progression and treatment success. ART antiretroviral treatment, HS health state

Fig. 2

Baseline and evolution of the mean Physical and Mental Component Summary (NAMSAL ANRS 12313 trial, n = 575). Baseline and evolution between baseline and W96 of the mean PCS (a) and MCS (b) in the DTG and EFV400 arms. Both scores range from 0 to 100, with higher values corresponding to better health-related quality of life. No significant differences were found between arms at any time point for both the PCS and MCS. The PCS increased by 11.9% (p < 0.0001) and 9.0% (p < 0.0001) in the DTG and EFV400 arm, respectively. The MCS increased by 8.0% (p = 0.0001) and 7.5% (p < 0.0001) in the DTG and EFV400 arms, respectively. DTG dolutegravir, EFV400 efavirenz 400 mg, HIV human immunodeficiency virus, MCS mental component summary, NAMSAL New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries, PCS physical component summary, W week

Fig. 3

Baseline and evolution of the proportions of patients with at least mild depression, anxiety, and stress (NAMSAL ANRS 12313 trial, n = 575). Baseline and evolution between baseline and W96 of the proportions of patients with at least mild depression (a), mild anxiety (b), and mild stress (c), assessed using the DASS-21 scale, in the DTG and EFV400 arms. No significant differences were found between arms at any time point for all three outcomes. The decrease of the proportion between baseline and W96 of patients with at least mild depression and mild anxiety was significant in both arms. However, the decrease in the proportion of patients with at least mild stress between baseline and W96 was not significant in the DTG arm (p = 0.24) and in the EFV400 arm (p = 0.054). DASS-21 Depression, Anxiety and Stress Scale—21 items, DTG dolutegravir, EFV400 efavirenz 400 mg, HIV human immunodeficiency virus, NAMSAL New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries, W week

Fig. 4

Cost-effectiveness plane and acceptability curve of DTG- vs low-dose EFV-based regimen (NAMSAL ANRS 12313 trial). a Cost-effectiveness plane depicting the 5000 simulated pairs of incremental costs and QALYs of DTG vs EFV400, with the hollow diamond representing the base-case estimate (ΔCosts = − US$27.8; ΔQALYs = 0.000). b Cost-effectiveness acceptability curve showing the probability of DTG being cost-effective compared with EFV400 at various thresholds ranging from 0 to US$10,000/QALY. In both figures, the short-dashed line, the long-dashed line, and the dashed-dotted line indicate the cost-effectiveness thresholds of US$500/QALY and one (US$1392/QALY) and three (US$4175/QALY) times the 2016 Cameroonian GDP per capita, respectively. DTG dolutegravir, EFV efavirenz, EFV400 efavirenz 400 mg, GDP gross domestic product, HIV human immunodeficiency virus, NAMSAL New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries, Q quadrant, QALY quality-adjusted life-year, Δ difference

Fig. 5

Cost-effectiveness price thresholds for DTG- and low-dose EFV-based regimens (NAMSAL ANRS 12313 trial). CE price thresholds for DTG- and EFV400-based regimens indicating which regimen would be preferred at the threshold of US$500 per QALY gained, and for any price combination of DTG and EFV400 FDC. The price combinations on the hollow circle line would make DTG CE with a probability of 95%. Any price combination on the solid triangle line would make EFV400 CE with a probability of 95%. The solid circle line depicts the price combinations for which both strategies have the same probability of being CE: Prob(DTG:CE) = Prob(EFV400:CE) = 50%. CE cost-effective, DTG dolutegravir, EFV efavirenz, EFV400 efavirenz 400 mg, FDC fixed-dose combinations, HIV human immunodeficiency virus, NAMSAL New Antiretroviral and Monitoring Strategies in HIV-infected Adults in Low-Income Countries, Prob probability, QALY quality-adjusted life-year