Treatment of Advanced HIV in the Modern Era

Abstract

Antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection from a fatal illness into a manageable chronic condition. However, despite remarkable progress, the HIV epidemic remains a global health challenge, with ambitious targets such as 95-95-95 by 2030 at risk of being unmet. While antiretroviral therapy availability has expanded worldwide, gaps persist, including unawareness of HIV status, inconsistent medication uptake, and limited engagement in care across diverse settings. Advanced HIV represents a particularly challenging yet underexplored aspect of HIV care. Its definition is complex, complicating efforts to address the needs of this vulnerable population. This review characterizes advanced HIV populations, defines them by spectra of immune suppression, antiretroviral therapy exposure, and drug resistance, and explores contemporary approaches to their management, with a particular focus on drug resistance and its clinical implications in modern HIV care. It highlights the unique challenges faced by individuals presenting late to care, those with limited care engagement, and aging populations with long-term exposure to HIV and antiretroviral therapy. By defining these populations, refining our understanding of advanced HIV, and addressing the diverse needs of affected individuals, providers can enhance outcomes and develop strategies to overcome barriers to care. Bridging these critical gaps is essential to advancing global efforts to end the HIV epidemic, both in the USA and worldwide.

The spectra of advanced HIV scenarios.

The figure depicts qualitatively the parameters considered here to define the three populations with advanced HIV, including time since diagnosis, immunological status, and drug resistance (axes). These populations exist on overlapping continuums of these parameters (axes planes). The three ellipsoids represent the scenarios discussed in this Review, including ‘Late presenters’ - low CD4, short time since HIV diagnosis, and low ART exposure and drug resistance; ‘limited care engagement’ - low CD4, intermediate to long time since HIV diagnosis, and high ART exposure and drug resistance; and ‘aging with HIV’ – intermediate to high CD4, long time since HIV diagnosis, and high ART exposure and drug resistance. The three-dimensionality of the ellipsoids is represented by their shadows on the axes planes.