title: Low antigen-specific CD4 T-cell immune responses despite normal absolute CD4 counts after long-term antiretroviral therapy an African cohort.
abstract: BACKGROUND
  CD4 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  CD4 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.
  
  
  CONCLUSIONS
  Seven 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.
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. Electronic address: rosemagala@yahoo.com.
authors.forename: Rose
authors.initials: R
authors.lastname: Nabatanzi
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. Electronic address: baylois@gmail.com.
authors.forename: Lois
authors.initials: L
authors.lastname: Bayigga
authors.affiliation: Department of Internal Medicine, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda. Electronic address: ssinabulyaisaac@gmail.com.
authors.forename: Isaac
authors.initials: I
authors.lastname: Ssinabulya
authors.affiliation: Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: akiragga@idi.co.ug.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kiragga
authors.affiliation: Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: akambugu@idi.co.ug.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda. Electronic address: jolobo@yahoo.co.uk.
authors.forename: Joseph
authors.initials: J
authors.lastname: Olobo
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda; Department of Internal Medicine, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda; Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: moses.joloba@case.edu.
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.affiliation: Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda; Department of Internal Medicine, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda; Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: mkamya@infocom.co.ug.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: hmk@chs.mak.ac.ug.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Department of Internal Medicine, Makerere University College of Health Sciences, Makerere University, Kampala, Uganda; Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: dnakanjako@gmail.com.
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D000942:Antigens, Bacterial / Q000276:immunology* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D000942:Antigens, Bacterial; C573415:IFNG protein, human; C508594:IL2 protein, human; C508598:IL4 protein, human; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: ART; CD4 T-cell proliferation; Cytokine production; Immune recovery; Sub-Saharan Africa; Uganda