In this episode, our host, Dr. Paulo Sales, interviews Dr. Mike Saag to explore practical challenges and strategies to enhance adherence to antiretroviral therapy in people living with HIV. Among other topics, the relevance of CD4/CD8 ratios and other clinical monitoring parameters were discussed while linking them with synergistic neurobiological and inflammatory changes occurring when antiretroviral non-adherence and major depressive disorder coexist with clinical vignettes and questions posed by Drs. Reid Black and Brandon Benningfield, psychiatric residents.