Antiretroviral Therapy May Induce Microbiome Composition Shifts in HIV-Positive Individuals Nonresponsive to Treatment

Abstract

Infection with human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and affects an estimated 40 million people worldwide. Although no cure currently exists, modern treatment for HIV involves the use of antiretroviral therapy (ART), which prevents disease progression by suppressing viral replication. Despite the use of ART, some HIV-positive individuals are unable to maintain a suppressed viral load and, even when viral suppression is achieved, ART cannot restore the gut microbiome dysbiosis and increased inflammation associated with HIV infection. Though the effects of HIV and ART use on the gut microbiome have been investigated in several studies, whether the gut microbiota affects the efficacy of ART in suppressing viral load has yet to be explored. To determine whether the gut microbiota is associated with response to ART, we used a 16S rRNA sequencing dataset to assess gut microbiome composition and function in HIV-positive individuals who do or do not achieve viral suppression on first-line ART. We observed that the gut microbiome of ART-responsive individuals generally shared less differences with healthy controls before and after treatment initiation. Meanwhile, a subset of ART-nonresponsive individuals exhibited decreased alpha diversity, depletion of certain microbial taxa, a unique core microbiome, and downregulation of metabolic pathways. Overall, our results suggest a possible association between the gut microbiome and ART efficacy, highlighting the need for further investigation with larger cohorts to fully elucidate this correlation, which could be used to inform treatment strategies to improve therapeutic outcomes with ART.