Low antigen-specific CD4 T-cell immune responses despite normal absolute CD4 counts after long-term antiretroviral therapy an African cohort

Abstract

BackgroundCD4 counts guide antiretroviral therapy (ART) initiation and prophylaxis for opportunistic infections. It is unclear whether normal CD4 counts translate to normalized immune responses among ART-treated adults. We compared antigen-specific CD4 T-cell immune responses among ART-treated adults with CD4≥500cells/μl, optimal immune responders (O-IR), and their age-matched healthy HIV-negative counterparts. MethodsIn a sample-based case–control study, cryopreserved peripheral blood mononuclear cells from 15 O-IR after 7 years of ART and 15 healthy controls, were analyzed for CD4+ T-cell proliferation using CFSE dye and cytokine production. ResultsCD4 T-cell proliferation, upon stimulation with PPD and pneumococcal polysaccharide antigen, was lower among O-IR relative to HIV-negative controls; p=0.016 and p=0.016 respectively. CD4 T-cell production of IL-2 was lower among O-IR relative to HIV-negative control p=0.002. CD4 T-cell proliferation upon stimulation with SEB and CMV antigens was similar among O-IR and HIV-negative controls p=0.971 and p=0.480, respectively, and so was IL-4 and IFN γ production; p=0.528 and p=0.892, respectively. ConclusionSeven years of suppressive ART caused partial CD4 T-cell function recovery in an African HIV treatment cohort, despite restoration of CD4 T-cell counts to levels≥500cells/μl. The role innate immunity in the recovery of immune function during long-term ART should be investigated to guide decisions on continued prophylaxis against opportunistic infections.