Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?

Abstract

Purpose of review: In the absence of a prophylactic/therapeutic vaccine or cure, the most amazing achievement in the battle against HIV was the discovery of effective, well-tolerated combination antiretroviral therapy (cART). The primary research question remains whether PLWH on prolonged successful therapy has accelerated, premature, or accentuated biological aging. In this review, we discuss the current understanding of the immunometabolic profile in PLWH, potentially associated with biological aging, and a better understanding of the mechanisms and temporal dynamics of biological aging in PLWH.

Recent findings: Biological aging, defined by the epigenetic alterations analyzed by the DNA methylation pattern, has been reported in PLWH with cART that points towards epigenetic age acceleration. The hastened development of specific clinical geriatric syndromes like cardiovascular diseases, metabolic syndrome, cancers, liver diseases, neurocognitive diseases, persistent low-grade inflammation, and a shift toward glutamate metabolism in PLWH may potentiate a metabolic profile at-risk for accelerated aging.

Keywords: Antiretroviral therapy; Biological aging; Immunometabolism; People living with HIV.

Fig. 1

Proposed metabolic reprogramming of T cells and myeloid cells in PLWH on cART based on current literature. Black lines describe pathways with high activation, while grey lines describe pathways with low activation in the cells. This collectively gives an overview of the metabolic pathways on which the different cell types are less dependent. The metabolites glutamine, lactate, glucose, and glutamate are marked in orange, blue, green, and pink, respectively. Their relative intracellular/extracellular abundance is represented based on the localization of the metabolite in the figure. The figure was created using Biorender.com and adapted from Svensson Akusjärvi S: Immunometabolic reprogramming during suppressive HIV-1 infection. Doctoral Thesis, Karolinska Institute 2022 [86]

Fig. 2

Alterations in metabolite levels in PLWH on cART compared to HC in cohorts from Cameroon (C), India (I), and Sweden (S) from targeted plasma metabolomics. Green boxes represent decreased metabolites in the PLWH on the cART group, while red boxes represent metabolites enriched at p < 0.05. Grey boxes represent metabolites that were not significantly different between the groups. The figure was adapted from Svensson Akusjärvi S: Immunometabolic reprogramming during suppressive HIV-1 infection. Doctoral Thesis, Karolinska Institute 2022 [86]