The long-term impact and value of curative therapy for HIV: a modelling analysis

Abstract

Introduction: Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long-term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country-specific value-based prices (VBPs) of CTx.

Methods: We developed a decision-analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre-existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low-and-middle-income countries and five high-income countries, accounting for localized ART and other HIV-related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability-adjusted life-years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long-term outcomes and each country's estimated health opportunity cost, we calculated the country-specific VBP of CTx.

Results: The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life-years, reduced the number of individuals on ART, reduced AIDS-related deaths, and ultimately led to fewer DALYs versus ART-alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to $812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater.

Conclusions: Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country.

Keywords: antiretroviral therapy (ART); cost-utility analysis (CUA); curative therapy (CTx); human immunodeficiency virus (HIV); low- and middle-income countries (LMICs); value-based price (VBP).

Figure 1

HIV state transition model. Individuals could transition from uninfected to an HIV health state or from one HIV health state to another. Individuals automatically transitioned from early HIV infection to chronic HIV after a single semi‐annual model cycle. In the CTx+ART comparator arm, eligible individuals could receive CTx. As determined, however, by the modelled durability of CTx cure, they could transition to a relapsed HIV health state with costs and disability weights equivalent to chronic HIV until they either received another CTx administration or died. Individuals could transition to death via AIDS‐associated mortality or the background mortality of the modelled country.

Figure 2

Model predicted HIV prevalence, ART coverage, and AIDS deaths for pre‐ and post‐introduction of gene therapy cure. ART coverage refers to the percentage of adults and children living with HIV currently receiving antiretroviral combination therapy in accordance with the nationally approved treatment protocols (or WHO/UNAIDS standards), antiretroviral regimens prescribed for post exposure prophylaxis are excluded, among the total estimated number of adults and children living with HIV.

Figure 2

Model predicted HIV prevalence, ART coverage, and AIDS deaths for pre‐ and post‐introduction of gene therapy cure. ART coverage refers to the percentage of adults and children living with HIV currently receiving antiretroviral combination therapy in accordance with the nationally approved treatment protocols (or WHO/UNAIDS standards), antiretroviral regimens prescribed for post exposure prophylaxis are excluded, among the total estimated number of adults and children living with HIV.

Figure 3

One‐way sensitivity analyses of value‐based price: top 20 most influential parameters. In one‐way sensitivity analysis, one parameter at a time is varied to its plausible low and high values while keeping all other parameters constant.