Cost-Effectiveness of Long-Acting Injectable HIV Preexposure Prophylaxis in the United States : A Cost-Effectiveness Analysis

Abstract

Background: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP).

Objective: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States.

Design: Simulation, cost-effectiveness analysis.

Data sources: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed.

Target population: 476 700 MSM/TGW at very high risk for HIV (VHR).

Time horizon: 10 years.

Perspective: Health care system.

Intervention: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP.

Outcome measures: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP.

Results of base-case analysis: Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year).

Results of sensitivity analysis: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year).

Limitation: Uncertain clinical and economic benefits of averting future transmissions.

Conclusion: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA.

Primary funding source: FHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.

Figure 1.

Annual costs reported over 10 years for MSM/TGW at VHR in the US (n=476,700) Panels depict the projected total annual component costs for each PrEP strategy (Panel A: No PrEP; Panel B: generic F/TDF; Panel C: branded F/TAF; and Panel D: CAB-LA). Time 1 on the horizontal axis represents the first year since the start of the model simulation. The left vertical axis shows annual total cost in billion 2020 US dollars. Annual component costs are given by the solid colors (ART drug: dark purple; HIV care: light purple; PrEP drug: dark blue; PrEP program: light blue) at any given yearly timepoint in the model simulation period (horizontal axis). For example, during Year 5 in Panel B, total annual cost was $2.47B (ART drug: $2.00B, HIV care: $326.38M, PrEP drug: $59.83M, PrEP program: $84.13M). Component costs for the cohort of MSM/TGW at high risk for HIV follow a similar pattern and are presented in Appendix Figure 6. Abbreviations: ART, antiretroviral therapy; CAB-LA, long-acting injectable cabotegravir; F/TAF, emtricitabine/tenofovir alafenamide fumarate; F/TDF, emtricitabine/tenofovir disoproxil fumarate; MSM/TGW, men who have sex with men / transgender women; PrEP, pre-exposure prophylaxis; VHR, very high risk for HIV.

Figure 2.

Sensitivity analysis: Maximum price premiums of CAB-LA PrEP over generic F/TDF at different willingness-to-pay thresholds for MSM/TGW at VHR (n=476,700) and HR (n=1,906,800) in the US over 10 years This figure presents a sensitivity analysis on maximum price premiums of CAB-LA PrEP at different willingness-to-pay thresholds. The vertical axis reports the maximum price premiums of CAB-LA over generic F/TDF. The horizontal axis reports willingness-to-pay thresholds, up to $300,000/QALY. Among VHR (blue line), at generic F/TDF price of $360/year, CAB-LA would achieve an ICER ≤$100,000/QALY with a maximum price premium of $3,700/year over generic F/TDF (CAB-LA price $4,100/year). As the willingness-to-pay threshold increases, the maximum price premium increases. For the $300,000/QALY threshold, the maximum price premium of CAB-LA would be $6,600/year (CAB-LA price $7,000/year). For the HR cohort (orange line), holding constant the generic F/TDF price of $360/year, the ICER of CAB-LA would be ≤$300,000/QALY at a maximum price premium of $2,100 (CAB-LA price $2,500/year). Abbreviations: CAB-LA, long-acting injectable cabotegravir; F/TDF, emtricitabine/tenofovir disoproxil fumarate; HR, high risk for HIV; ICER, incremental cost effectiveness ratio; MSM/TGW, men who have sex with men / transgender women; PrEP, pre-exposure prophylaxis; QALY, quality-adjusted life-year; VHR, very high risk for HIV.

Figure 3.

Cost-effectiveness of CAB-LA vs. generic F/TDF sensitivity analysis: Maximum price premiums for combinations of CAB-LA efficacy and CAB-LA PrEP program retention among MSM/TGW at A) VHR (n=476,700) and B) HR (n=1,906,800) in the US This figure shows the maximum price premium at which CAB-LA vs. generic F/TDF would be cost-effective at each combination of CAB-LA efficacy and CAB-LA PrEP program retention. Drug prices of generic F/TDF ($360) and CAB-LA ($25,850) are held constant. In the base case, for the VHR (white X, Panel A), the ICER of CAB-LA would be ≤$100,000/QALY at a maximum price premium of $3,700 (i.e., generic F/TDF price of $360 and CAB-LA price of $4,100). Although the price premium is $3,700/year in the base case, it would be <$5,500/year when relative improvement in efficacy of CAB-LA over F/TDF is 90% and 6-year retention is 42% (white circle). For the HR cohort, holding constant 28% 6-year retention and 80% relative improvement in efficacy of CAB-LA over F/TDF (black X, Panel B), the ICER of CAB-LA would be $100,000/QALY at a maximum price premium of $1,100 (i.e., generic F/TDF price of $360 and CAB-LA price of $1,500). Abbreviations: CAB-LA, long-acting injectable cabotegravir; F/TDF, emtricitabine/tenofovir disoproxil fumarate; HR, high risk for HIV; ICER, incremental cost effectiveness ratio; MSM/TGW, men who have sex with men / transgender women; QALY, quality-adjusted life-year; VHR, very high risk for HIV.