Older age is associated with peripheral blood expansion of naïve B cells in HIV-infected subjects on antiretroviral therapy

Abstract

Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.

Figure 1. Absolute B cell phenotype counts before and after antiretroviral therapy.

Changes in absolute B cell count and B cell subset counts at baseline before ART (light grey) and after 192 weeks of ART (dark grey) compared to their age-matched controls (black) in older and younger groups. Only the significant P-values are marked. Bars represent median; error bars represent interquartile ranges. RM: resting memory, TLM: tissue like memory, MA: mature activated, IT: immature transitional.

Figure 2. B cell phenotype distribution before and after antiretroviral therapy.

Change in phenotype distribution in old and young age groups compared with their respective age-matched controls. 0 and 192 refer to time on ART in weeks; Ctl refer to respective age matched uninfected controls.

Figure 3. Correlations between antibody responses to vaccines and resting memory count at baseline in HIV infected and uninfected controls.

a. Tetanus vaccine b. Hepatitis A vaccine.