Abstract
The goal of this research was to establish a new and innovative framework for cost-effectiveness modeling of HIV-1 treatment, simultaneously considering both clinical and epidemiological outcomes. EPICE-HIV is a multi-paradigm model based on a within-host micro-simulation model for the disease progression of HIV-1 infected individuals and an agent-based sexual contact network (SCN) model for the transmission of HIV-1 infection. It includes HIV-1 viral dynamics, CD4+ T cell infection rates, and pharmacokinetics/pharmacodynamics modeling. Disease progression of HIV-1 infected individuals is driven by the interdependent changes in CD4+ T cell count, changes in plasma HIV-1 RNA, accumulation of resistance mutations and adherence to treatment. The two parts of the model are joined through a per-sexual-act and viral load dependent probability of disease transmission in HIV-discordant couples. Internal validity of the disease progression part of the model is assessed and external validity is demonstrated in comparison to the outcomes observed in the STaR randomized controlled clinical trial. We found that overall adherence to treatment and the resulting pattern of treatment interruptions are key drivers of HIV-1 treatment outcomes. Our model, though largely independent of efficacy data from RCT, was accurate in producing 96-week outcomes, qualitatively and quantitatively comparable to the ones observed in the STaR trial. We demonstrate that multi-paradigm micro-simulation modeling is a promising tool to generate evidence about optimal policy strategies in HIV-1 treatment, including treatment efficacy, HIV-1 transmission, and cost-effectiveness analysis.
Highlights
As a result of the introduction of increasingly potent and safe anti-retroviral therapy (ART), over the last decade HIV-1 infection has largely become a manageable disease, with mortality rates approaching those of the general population in many countries [1,2,3]
The present analysis focuses on the HIV-1 dynamics model (HIV-D) model and the implementation of the primary treatment regimen in the within-host model
In the absence of drug effect, the HIV-D model simulates CD4+ T cell counts and plasma HIV-1 RNA levels as a function of time for HIV-1 infected individuals that pass through the 3 typical stages of HIV-1 infection: acute infection, clinical latency and AIDS phase (Fig 3) [52]
Summary
As a result of the introduction of increasingly potent and safe anti-retroviral therapy (ART), over the last decade HIV-1 infection has largely become a manageable disease, with mortality rates approaching those of the general population in many countries [1,2,3]. PLOS ONE | DOI:10.1371/journal.pone.0149007 February 12, 2016
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
