Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

Abstract

Despite effective antiretroviral therapy (ART), people living with HIV (PLWH) still present persistent chronic immune activation and inflammation. This condition is the result of several factors including thymic dysfunction, persistent antigen stimulation due to low residual viremia, microbial translocation and dysbiosis, caused by the disruption of the gut mucosa, co-infections, and cumulative ART toxicity. All of these factors can create a vicious cycle that does not allow the full control of immune activation and inflammation, leading to an increased risk of developing non-AIDS co-morbidities such as metabolic syndrome and cardiovascular diseases. This review aims to provide an overview of the most recent data about HIV-associated inflammation and chronic immune exhaustion in PLWH under effective ART. Furthermore, we discuss new therapy approaches that are currently being tested to reduce the risk of developing inflammation, ART toxicity, and non-AIDS co-morbidities.

Keywords: ART; HIV; immune activation; inflammation; metabolic syndrome; non-AIDS co-morbidities; premature aging.

Figure 1

HIV infection causes both mucosal disruption and depletion of CD4+ T cells in gut-associated lymphoid tissue (GALT), altering the microbial composition (dysbiosis) and allowing microbial product to enter the circulatory system. Even with the introduction of antiretroviral therapy (ART), these two mechanisms lead to chronic immune activation and persistent inflammation that could also be enhanced by opportunistic co-infections. In turn, chronic activation and persistent inflammation result in (i) immune exhaustion and premature immune senescence, and in (ii) a direct damage of organs, through the release of pro-inflammatory cytokines. Images were obtained from Servier Medical Art images (http://smart.servier.com/).

Figure 2

HIV causes persistent inflammation and chronic immune activation. Over the years and despite effective ART, this altered immunological status could lead to the development of non-AIDS co-morbidities in people living with HIV (PLWH). Many of these are identified as cardiovascular diseases (CVDs) or metabolic syndrome (MetS). NADCs: non-AIDS-defining cancers; HALS: HIV-associated lipodystrophy syndrome; MHO: metabolically healthy obesity; ROS: reactive oxygen species; BMI: body mass index. Images were obtained from Servier Medical Art images (http://smart.servier.com/).