Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Institute of Applied Mathematics, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS Comput Biol. 2018 Apr 26;14(4):e1006129. doi: 10.1371/journal.pcbi.1006129. eCollection 2018 Apr.
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.
患有单纯疱疹病毒 2 型（HSV-2）感染的患者面临更高的感染人类免疫缺陷病毒 1 型（HIV-1）的风险。这被认为是由于疱疹病变充当 HIV-1 的进入点，并且在 HSV-2 病变事件期间组织驻留的 CD4+T 细胞计数增加。我们创建了一个随机和空间数学模型，描述了生殖器黏膜中 HSV-2 感染和免疫反应的动力学。使用我们的模型，我们首先研究了正在发展的 HSV-2 病变的动力学。然后，我们使用我们的模型来量化在 HSV-2 阳性女性中通过性接触感染 HIV-1 的风险。未治疗时，我们发现 HSV-2 感染的女性感染 HIV-1 的可能性比健康患者高 8.6 倍。然而，当包括 HSV-2 抗病毒药物普立万的作用时，根据药物剂量，HIV-1 感染的风险预计会降低多达 35%。我们估计减少组织损伤与减少 CD4+细胞存在对确定普立万在降低 HIV-1 感染方面的有效性的相对重要性。我们的研究结果表明，应进行临床试验来评估普立万或类似药物在预防 HSV-2 阳性女性中 HIV-1 感染的有效性。
