Cost-Effectiveness of Preemptive Switching to Efavirenz-Based Antiretroviral Therapy for Children With Human Immunodeficiency Virus

Sophie Desmonde, Simone C Frank, Ashraf Coovadia, Désiré L Dahourou, Taige Hou, Elaine J Abrams, Madeleine Amorissani-Folquet, Rochelle P Walensky, Renate Strehlau, Martina Penazzato, Kenneth A Freedberg, Louise Kuhn, Valeriane Leroy, Andrea L Ciaranello, Sophie Desmonde, Simone C Frank, Ashraf Coovadia, Désiré L Dahourou, Taige Hou, Elaine J Abrams, Madeleine Amorissani-Folquet, Rochelle P Walensky, Renate Strehlau, Martina Penazzato, Kenneth A Freedberg, Louise Kuhn, Valeriane Leroy, Andrea L Ciaranello

Abstract

Background: The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d'Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus-infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model.

Methods: We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (<1000 copies/mL) after a switch to EFV (98.4%) and the subsequent risk of virologic failure (LPV/r, 0.23%/mo; EFV, 0.15%/mo) from NEVEREST-3 data; we obtained ART costs (LPV/r, $6-$20/mo; EFV, $3-$6/mo) from published sources. We projected discounted life expectancy (LE) and lifetime costs per person. A secondary analysis used data from MONOD-ANRS-12206 in Côte d'Ivoire.

Results: Continued LPV/r led to the shortest LE (18.2 years) and the highest per-person lifetime cost ($19 470). LPV/r with second-line option increased LE (19.9 years) and decreased per-person lifetime costs($16 070). Switching led to the longest LE (20.4 years) and the lowest per-person lifetime cost ($15 240); this strategy was cost saving under plausible variations in key parameters. Using MONOD-ANRS-12206 data in Côte d'Ivoire, the Switch strategy remained cost saving only compared with continued LPV/r, but the LPV/r with second-line option strategy was cost-effective compared with switching.

Conclusion: For children ≥3 years old and virologically suppressed by LPV/r-based ART, preemptive switching to EFV can improve long-term clinical outcomes and be cost saving.

Clinical trials registration: NCT01127204.

Keywords: Africa; HIV; cost-effectiveness; pediatrics; treatment strategies.

Figures

Figure 1.
Figure 1.
Diagram of the 3 modeled strategies. Continued LPV/r represents the current practice in most sub-Saharan African settings, where no alternative option is available after ritonavir-boosted lopinavir (LPV/r) failure. LPV/r with second-line option represents the current World Health Organization recommendations, where children failing first-line LPV/r should be switched to second-line antiretroviral therapy (ART). In the base case, we assumed this second-line option would be non-nucleoside reverse-transcriptase inhibitor based, with virologic outcomes shown here; we varied these virologic outcomes and costs widely to reflect other second-line ART options, including dolutegravir. The “switch” strategy is the strategy evaluated in the NEVEREST-3 and MONOD-ANRS-12206 trials. Abbreviations: EFV, efavirenz; VF, virologic failure.
Figure 2.
Figure 2.
Multivariate sensitivity analyses: impact of simultaneous variation in monthly risk of late failure on preemptive switch to efavirenz (EFV) or first-line ritonavir-boosted lopinavir (LPV/r). The monthly risk of late failure of the preemptive EFV-based regimen is shown on the vertical axis; the monthly risk of late failure on the first-line LPV/r-based regimen is shown on the horizontal axis. This figure shows results comparing the switch strategy with that of LPV/r with second-line option (availability of nonnucleoside reverse-transcriptase inhibitor–based second-line antiretroviral therapy in case of failure with LPV/r). Costs and life-years are discounted at 3% per year. Following World Health Organization gross domestic product (GDP)–based guidance, cost-effectiveness results support the choice of switching in the green-shaded scenarios and the choice of LPV/r with second-line option in the red-, orange-, and yellow-shaded scenarios. Abbreviation: ICER, incremental cost-effectiveness ratio.
Figure 3.
Figure 3.
Multivariate sensitivity analyses of the impact of simultaneous variation in characteristics of the antiretroviral therapy (ART) regimen after failed ritonavir-boosted lopinavir (LPV/r) in the LPV/r with second-option strategy, including initial suppression, monthly risk of late failure, and costs. In each panel, the monthly risk of late failure of the ART regimen that would follow LPV/r failure in the LPV/r with second-line option strategy is shown on the vertical axis, and the initial 24-week suppression with that regimen is shown on the horizontal axis. The top left panel shows base case ART costs for this regimen. The top right panel shows results when the cost of this regimen is reduced by half. The bottom panel shows results when the cost is doubled. Green shading indicates scenarios in which the switch strategy is cost saving (leading to greater life expectancy and lower lifetime costs), compared with LPV/r with second-line option; pale green shading indicates that the LPV/r with second-line option strategy projects the longest life expectancy but is not cost-effective, and the switch strategy is economically preferred. Orange shading indicates scenarios wherein LPV/r with second-line option is cost-effective compared with the switch strategy. Costs and life-years are discounted at 3% per year. Abbreviations: EFV, efavirenz; GDP, gross domestic product; ICER, incremental cost-effectiveness ratio.

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