Chronic inflammation in a long-term cohort of HIV-infected patients according to the normalization of the CD4:CD8 ratio

Abstract

In HIV-infected patients a low CD4:CD8 ratio can persist despite CD4 recovery with long-term antiretroviral treatment (ART). As CD4:CD8 inversion is considered a marker of immune-senescence, we aimed to assess if it was associated with the chronic inflammation state in aging patients with HIV. A total of 112 patients with a >15 year history of HIV infection and ART were included, 85 of whom were suppressed. All subjects were tested for interleukin (IL)-6, high-sensitivity (hs)-PCR, and D-dimer levels. Complete clinical, therapeutic, and hematochemical data were retrieved. Coreceptor tropism based on HIV-DNA gp120 genotyping was also available within the past 6 months. A progressive increase in the CD4:CD8 ratio over time was observed without reaching a plateau. Based on the CD4:CD8 ratio at the time of testing, patients were classified into group A (normal ratio ≥0.9) and group B (<0.9). A normal ratio was observed in 37% of patients. Variables associated with an inverted CD4:CD8 ratio were older age, nadir CD4, and detectable HIV viremia. No association between HIV subtype, coreceptor tropism, cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) coinfections and CD4:CD8 ratio was observed. Group B patients showed a trend for a higher frequency of diabetes and hypertriglyceridemia compared to group A patients, but they did not differ in IL-6, hs-PCR, and D-dimer levels or in frequency of severe non-AIDS-associated events. In conclusion, CD4:CD8 ratio normalization occurs rarely, even after several years of ART. Chronic inflammation in patients aging with HIV does not seem to be directly dependent on the CD4:CD8 ratio. However, the persistent immune dysregulation expressed by a CD4:CD8 inversion might be linked to a higher risk of non-AIDS events, especially metabolic disorders.