CDd4 t- cell immune responses in haart-treated hiv-infected adults who attain normal CD4 counts in a Ugandan cohort

Abstract

Background: Majority of HIV-infected individuals who start HAART at CD4 counts <200 cells/µl show a marked CD4+T-cell increase to absolute CD4 counts above 500 cells/µl. The CD4+ T-cell count is the main measure for immune status of HIV-infected persons used by clinicians to initiate and monitor HAART as well as prophylaxis for opportunistic infections, although absolute CD4 counts may not indicate functionality of specific immune responses. We compared the CD4+T-cell proliferation and cytokine production among HAART-treated optimal immune responders (OIR) and their age-matched HIV-negative counterparts to determine whether host T-cell immune responses recover to levels comparable to healthy HIV-negative individuals. Methods: A case control study that utilized previously collected frozen peripheral blood mononuclear cells (PBMCs) from a cohort of HIV-infected adults that initiated HAART at CD4<200 cells/μl at the Infectious Diseases Institute, Makerere University. Cases were ‘Optimal’ responders (patients with suppressed viremia that attained CD4 counts>500 cells/µl after 7 years of HAART and controls were Healthy age-matched HIV negative adults within the Mulago hospital routine HIV testing program. CD4+ T-cell proliferation using CFSE dye, upon stimulation with SEB, PPD, pneumococcal polysaccharide antigen and CMV, were measured and compared among 15 cases (optimal responders) and 15 controls (HIV-negative individuals). CD4+ T-cell proliferation and cytokine production were compared among OIR and HIV-negative individuals, using Mann–Whitney U-test for non-parametric variables. Data analysis was done using FLOWJO and Graph Pad Prism 6 and p values<0.05 were considered statistically significant. Results: Percentage of proliferated CD4 T-cells upon stimulation with PPD and pneumococcal polysaccharide antigen were lower among Optimal immune responders relative to HIV-negative controls; p=0.0162 and p=0.0164 respectively. In addition, CD4 T-cell production of IL-2 was lower among OIR relative to HIV-negative control p= 0.002 .The percentage of proliferated CD4T-cells upon stimulation with SEB and CMV antigens was similar among OIR and HIV-negative controls p=0.971 and p=0.480, respectively. CD4 T-cell production of IL-4 and IFN γ was comparable between the two groups p=0.5281 and p= 0.8916, respectively . Conclusions: Seven years of suppressive HAART did not restore immune responses to levels comparable to healthy HIV-negative individuals. There is need for interventions to optimize immune recovery among individuals that initiate HAART at advanced stages of HIV disease.