Abstract
Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed a numerical method that allows predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the method to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approach is verified against state-of-the-art stochastic simulation. While the method is more accurate than stochastic simulation, it is superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The method's computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.
Highlights
Since its transfer to human in the early 20th century [1], human immunodeficiency virus (HIV) remains a major public health threat
We introduce a numerical method to directly compute the prophylactic efficacy from a viral dynamics model, without the need for sampling
Based on several examples with dolutegravir (DTG) -based short- and long-term Pre-exposure prophylaxis (PrEP), as well as post-exposure prophylaxis we demonstrate the correctness of the new method and its outstanding computational performance
Summary
Since its transfer to human in the early 20th century [1], HIV remains a major public health threat. According to UNAIDS estimates, approximately 38 million individuals worldwide are infected with the human immunodeficiency virus (HIV) [2]. HIV continues to spread and the latest incidence estimates amount to about 1.7 million new infections in 2019 [2]. About 30 antiviral compounds are available that can stop HIV replication and prevent the acquired immunodeficiency symdrome (AIDS) and AIDS-related death [4]. Unlike many other infections, no cure is available to clear HIV, which can persist in latent reservoirs for decades [5, 6]. Available treatments have to be taken life-long to prevent the relapse of virus from latent reservoirs and to prevent AIDS. Based on the successes in antiviral drug discovery, recent years have seen an increasing interest in utilising antivirals for treatment, and to prevent HIV transmission. Two general strategies are currently implemented for this purpose: (i) Treatment-as-prevention (TasP) intends to put individuals with an HIV diagnosis immediately on treatment, which essentially makes them non-contagious by decreasing the number of viruses they can expose to uninfected individuals [8]. (ii) Pre-exposure prophylaxis (PrEP) on the other hand prevents establishment of HIV infection after exposure [9, 10]
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