Genetic Signatures of Immune Recovery in People Living with HIV on Long-Term Contemporary Antiretroviral Therapy

The advances in antiretroviral therapy (ART) bring forth an ever-growing percentage of aging people living with HIV (PLHIV) with successful immune restoration (SIR) but increased comorbidities and reduced quality of life. The current criteria for SIR, CD4 absolute count (AC) >500 cells/µL, are proving not to be sufficiently informative enough for preventing or monitoring these unwelcome changes. Messenger RNA (mRNA) of genes, such as CXCL8, IL-6, and CSF-2, that have shown relations with HIV/HIV-associated comorbidities could represent early indicators of increase in viral load and/or pathological changes leading development of comorbidities. Our results display an underexpression of CXCL8 and IL-6 in ART+ PLHIV with CD4 AC >1,000, but not with CD4 AC <1,000, compared to ART-PLHIV and lower levels of CSF-2 mRNA in ART+ CD4 AC >1,000 compared to ART+ CD4 AC <1,000. Taken together, these findings indicate the need to stratify and expand HIV monitoring beyond CD4 AC >500.