HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities

An increasing amount of evidence suggests that HIV replication persists in gut-associated lymphoid tissues (GALT), despite treatment with combination antiretroviral therapy (cART). Residual replication in this compartment may propagate infection at other sites in the body and contribute to sustained immune dysregulation and delayed immune recovery. Therefore, it is important to focus efforts on eliminating residual replication at this site. There are several challenges to accomplishing this goal, including low antiretroviral (ARV) exposure at specific tissue locations within GALT, which might be overcome by using the tools of clinical pharmacology. Here, we summarize the evidence for GALT as a site of residual HIV replication, highlight the consequences of persistent infection in tissues, identify current pharmacologic knowledge of drug exposure in GALT, define the challenges that hinder eradication from this site, and propose several avenues for pharmacologic intervention.