Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy.

Abstract

Background: People living with HIV (PLHIV) demonstrate accelerated aging and immunosenescence in spite of immune-restoration following long-term antiretroviral treatment (ART). Low level inflammation leading to inflammaging plays an important role in mediating premature immunosenescence. Ongoing viral replication, antiretrovirals and subclinical infections with the common viruses like Cytomegalovirus (CMV) are known to induce inflammaging. However such data is scarce in India where persistent low level inflammation is common in general population due to various subclinical infections. Hence we conducted a study to determine the extent of immunosenescence in asymptomatic PLHIV on long term ART in comparison with their age-matched controls.

Results: The study was conducted in asymptomatic virally suppressed PLHIV on ART for more than 5 years [n = 70, M: F = 36:34] and HIV uninfected controls [n = 68, M: F = 31:37] belonging to the age-group of 40-55 years. Blood samples were collected for assessing levels of immunosenescence markers on CD4 T cells by flow cytometry and anti-CMV antibodies as well as soluble CD14 (sCD14) levels by ELISA. The levels were compared between cases and controls and correlated with the levels of anti-CMV antibody and sCD14. PLHIV had significantly lower levels of naïve T cells and higher levels of activated and immunosenescent T cells than controls as indicated by CD38, CD57, CD28 expressing CD4 and CD8 T cells. PLHIV had higher levels of anti-CMV antibodies, but lower levels of sCD14 levels and HLADR + CD8 T cells than those in controls. Immunosenescent T cells correlated positively with anti-CMV antibody levels and negatively with sCD14 levels. Duration of dolutegravir based therapy correlated negatively with sCD14 levels.

Conclusions: Thus, higher levels of immune activation and immunosenescence in the cases possibly indicate their compromised immune status predisposing PLHIV to infections and cancers. The study indicated a need for CMV treatment regimens even in asymptomatic individuals for preventing immunosenescence. The study also indicated a role of dolutegravir induced loss of sCD14 levels in predisposing PLHIV to immunosenescence.