bay-57-1293 and HIV-Infections

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.

Topics: Antiviral Agents; CD4-Positive T-Lymphocytes; Computational Biology; Computer Simulation; Female; Genitalia, Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Models, Biological; Pyridines; Risk Factors; Sexual Behavior; Stochastic Processes; Sulfonamides; Thiazoles

Topics: Animals; Anti-HIV Agents; Antiviral Agents; Cytomegalovirus Infections; Drug Evaluation, Preclinical; Hepatitis B; Herpes Simplex; HIV Infections; Humans; Mice; Naphthalenesulfonates; Pyridines; Pyrimidines; Sulfonamides; Thiazoles; Virus Diseases