Investigating the effects of Doxycycline (DoxyPEP) on intra-rectal HIV acquisition

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

Bacterial, sexually transmitted infections are associated with poor health outcomes and increased risk of secondary viral acquisition. To curb these bacterial infections, clinicians have begun to prescribe high doses of the antibiotic doxycycline as post-exposure prophylaxis. Though effective at preventing bacterial infections, it is unknown whether repeated doxycycline use alters susceptibility to viral pathogens, influences the function of the host intestinal microbiome, or perturbs mucosal and systemic immunity. To address the effect of doxycycline on these parameters, we will repeatedly treat Asian macaques with doxycycline prior to low-dose viral challenges. We will longitudinally study the composition of the GI tract microbiome, the metabolome, and mucosal and systemic immunity in doxycycline-treated macaques. We will then challenge this cohort, with both doxycycline treatment and challenge to continue until infection is confirmed. We predict that repeated, prolonged doxycycline treatment will increase susceptibility to low-dose viral acquisition in otherwise healthy macaques. Data from this proposal will inform the long-term use of doxycycline in the context of viral exposure in the humans.