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Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

ABSTRACT: Born out of a necessity for fiscal sustainability, simulation modeling is playing an increasingly prominent role in setting priorities for combination implementation strategies for HIV treatment and prevention globally. The design of a model and the data inputted into it are central factors in ensuring credible inferences. We executed a narrative review of a set of dynamic HIV transmission models to comprehensively synthesize and compare the structural design and the quality of evidence used to support each model. We included 19 models representing both generalized and concentrated epidemics, classified as compartmental, agent-based, individual-based microsimulation or hybrid in our review. We focused on four structural components (population construction; model entry, exit and HIV care engagement; HIV disease progression; and the force of HIV infection), and two analytical components (model calibration/validation; and health economic evaluation, including uncertainty analysis). While the models we reviewed focused on a variety of individual interventions and their combinations, their structural designs were relatively homogenous across three of the four focal components, with key structural elements influenced by model type and epidemiological context. In contrast, model entry, exit and HIV care engagement tended to differ most across models, with some health system interactions-particularly HIV testing-not modeled explicitly in many contexts. The quality of data used in the models and the transparency with which the data was presented differed substantially across model components. Representative and high-quality data on health service delivery were most commonly not accessed or were unavailable. The structure of an HIV model should ideally fit its epidemiological context and be able to capture all efficacious treatment and prevention services relevant to a robust combination implementation strategy. Developing standardized guidelines on evidence syntheses for health economic evaluation would improve transparency and help prioritize data collection to reduce decision uncertainty.

SUBMITTER: Zang X

PROVIDER: S-EPMC6711792 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

Zang Xiao X Krebs Emanuel E Wang Linwei L Marshall Brandon D L BDL Granich Reuben R Schackman Bruce R BR Montaner Julio S G JSG Nosyk Bohdan B

PharmacoEconomics 20191001 10

Born out of a necessity for fiscal sustainability, simulation modeling is playing an increasingly prominent role in setting priorities for combination implementation strategies for HIV treatment and prevention globally. The design of a model and the data inputted into it are central factors in ensuring credible inferences. We executed a narrative review of a set of dynamic HIV transmission models to comprehensively synthesize and compare the structural design and the quality of evidence used to ...[more]

PMID: 31222521

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Project description:IntroductionThe development of a human immunodeficiency virus 1 (HIV-1) vaccine remains a formidable challenge. An effective vaccine likely requires the induction of broadly neutralizing antibodies (bNAbs), which likely involves the use of native-like HIV-1 envelope (Env) trimers at some or all stages of vaccination. Development of such trimers has been very difficult, but much progress has been made in the past decade, starting with the BG505 SOSIP trimer, elucidation of its atomic structure and implementing subsequent design iterations. This progress facilitated understanding the weaknesses of the Env trimer, fuelled structure-guided HIV-1 vaccine design and assisted in the development of new vaccine designs. This review summarizes the relevant literature focusing on studies using structural biology to reveal and define HIV-1 Env sites of vulnerability; to improve Env trimers, by creating more stable versions; understanding antibody responses in preclinical vaccination studies at the atomic level; understanding the glycan shield; and to improve "on-target" antibody responses versus "off-target" responses.MethodsThe authors conducted a narrative review of recently published articles that made a major contribution to HIV-1 structural biology and vaccine design efforts between the years 2000 and 2021.DiscussionThe field of structural biology is evolving at an unprecedented pace, where cryo-electron microscopy (cryo-EM) and X-ray crystallography provide complementary information. Resolving protein structures is necessary for defining which Env surfaces are accessible for the immune system and can be targeted by neutralizing antibodies. Recently developed techniques, such as electron microscopy-based polyclonal epitope mapping (EMPEM) are revolutionizing the way we are analysing immune responses and shed light on the immunodominant targets on new vaccine immunogens. Such information accelerates iterative vaccine design; for example, by reducing undesirable off-target responses, while improving immunogens to drive the more desirable on-target responses.ConclusionsResolving high-resolution structures of the HIV-1 Env trimer was instrumental in understanding and improving recombinant HIV-1 Env trimers that mimic the structure of viral HIV-1 Env spikes. Newly emerging techniques in structural biology are aiding vaccine design efforts and improving immunogens. The role of structural biology in HIV-1 vaccine design has indeed become very prominent and is unlikely to diminish any time soon.

Project description:BackgroundThe HIV epidemic remains a major public health problem. Critical to transmission control are HIV prevention strategies with new interventions continuing to be developed. Mathematical models are important for understanding the potential impact of these interventions and supporting policy decisions. This systematic review aims to answer the following question: when a new HIV prevention intervention is being considered or designed, what information regarding it is necessary to include in a compartmental model to provide useful insights to policy makers? The primary objective of this review is therefore to assess suitability of current compartmental HIV prevention models for informing policy development.MethodsArticles published in EMBASE, Medline, Econlit, and Global Health were screened. Included studies were identified using permutations of (i) HIV, (ii) pre-exposure prophylaxis (PrEP), circumcision (both voluntary male circumcision [VMMC] and early-infant male circumcision [EIMC]), and vaccination, and (iii) modelling. Data extraction focused on study design, model structure, and intervention incorporation into models. Article quality was assessed using the TRACE (TRAnsparent and Comprehensive Ecological modelling documentation) criteria for mathematical models.ResultsOf 837 articles screened, 48 articles were included in the review, with 32 unique mathematical models identified. The substantial majority of studies included PrEP (83%), whilst fewer modelled circumcision (54%), and only a few focussed on vaccination (10%). Data evaluation, implementation verification, and model output corroboration were identified as areas of poorer model quality. Parameters commonly included in the mathematical models were intervention uptake and effectiveness, with additional intervention-specific common parameters identified. We identified key modelling gaps; critically, models insufficiently incorporate multiple interventions acting simultaneously. Additionally, population subgroups were generally poorly represented-with future models requiring improved incorporation of ethnicity and sexual risk group stratification-and many models contained inappropriate data in parameterisation which will affect output accuracy.ConclusionsThis review identified gaps in compartmental models to date and suggests areas of improvement for models focusing on new prevention interventions. Resolution of such gaps within future models will ensure greater robustness and transparency, and enable more accurate assessment of the impact that new interventions may have, thereby providing more meaningful guidance to policy makers.

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Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

Publications

Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

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