Effects of spatiotemporal HSV-2 lesion dynamics and antiviral treatment on the risk of HIV-1 acquisition

Catherine M Byrne, Soren Gantt and Daniel Coombs

PLOS Computational Biology, 2018, vol. 14, issue 4, 1-28

Abstract: Patients with Herpes Simplex Virus-2 (HSV-2) infection face a significantly higher risk of contracting HIV-1. This is thought to be due to herpetic lesions serving as entry points for HIV-1 and tissue-resident CD4+ T cell counts increasing during HSV-2 lesional events. We have created a stochastic and spatial mathematical model describing the dynamics of HSV-2 infection and immune response in the genital mucosa. Using our model, we first study the dynamics of a developing HSV-2 lesion. We then use our model to quantify the risk of infection with HIV-1 following sexual exposure in HSV-2 positive women. Untreated, we find that HSV-2 infected women are up to 8.6 times more likely to acquire HIV-1 than healthy patients. However, when including the effects of the HSV-2 antiviral drug, pritelivir, the risk of HIV-1 infection is predicted to decrease by up to 35%, depending on drug dosage. We estimate the relative importance of decreased tissue damage versus decreased CD4+ cell presence in determining the effectiveness of pritelivir in reducing HIV-1 infection. Our results suggest that clinical trials should be performed to evaluate the effectiveness of pritelivir or similar agents in preventing HIV-1 infection in HSV-2 positive women.Author summary: The risk of contracting HIV-1 is significantly higher in people who have genital HSV-2 infections. Here, we put forward a new mathematical model to describe HSV-2 infection and the process of HIV-1 infection in the genital mucosa surrounding HSV-2 lesions. We determine how the characteristics of HSV-2 infection affect the risk of HIV-1 infection, and determine whether reducing the severity of HSV-2 symptoms with antiviral drugs can be expected to decrease the risk of HIV-1 infection. We find that the risk of HIV-1 infection is dependent on three factors: the amount of HIV-1 the patient is exposed to, the severity of HSV-2 lesions, and the number of CD4+ T immune cells in the genital mucosa. Our model predicts that antiviral drugs targeting HSV-2 can cause a therapeutic decrease in lesion severity and CD4+ T cell count in the genital mucosa. This furthermore causes a significant decrease in the risk of HIV-1 infection but the dose of HSV-2 antiviral drug must be sufficiently high. Our results support further development and testing of new HSV-2 antiviral drugs to help decrease the world-wide burden of HIV-1.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1006129

DOI: 10.1371/journal.pcbi.1006129

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