title: Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.
abstract: HIV-infected African adults are at a considerably increased risk of life-threatening invasive pneumococcal disease (IPD) which persists despite antiretroviral therapy (ART). Defects in naturally acquired pneumococcal-specific T-cell immunity have been identified in HIV-infected adults. We have therefore determined the extent and nature of pneumococcal antigen-specific immune recovery following ART. HIV-infected adults were followed up at 3, 6 and 12 months after initiating ART. Nasopharyngeal swabs were cultured to determine carriage rates. Pneumococcal-specific CD4 T-cell immunity was assessed by IFN-γ ELISpot, proliferation assay, CD154 expression and intracellular cytokine assay. S. pneumoniae colonization was detected in 27% (13/48) of HIV-infected patients prior to ART. The rates remained elevated after 12 months ART, 41% (16/39) (p = 0.17) and significantly higher than in HIV-uninfected individuals (HIVneg 14%(4/29); p = 0.0147). CD4+ T-cell proliferative responses to pneumococcal antigens increased significantly to levels comparable with HIV-negative individuals at 12 months ART (p = 0.0799). However, recovery of the pneumococcal-specific CD154 expression was incomplete (p = 0.0015) as were IFN-γ ELISpot responses (p = 0.0040) and polyfunctional CD4+ T-cell responses (TNF-α, IL-2 and IFN-γ expression) (p = 0.0040) to a pneumolysin-deficient mutant strain. Impaired control of pneumococcal colonisation and incomplete restoration of pneumococcal-specific immunity may explain the persistently higher risk of IPD amongst HIV-infected adults on ART. Whether vaccination and prolonged ART can overcome this immunological defect and reduce the high levels of pneumococcal colonisation requires further evaluation.
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors: Enoch
authors: E
authors: Sepako
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors: Sarah J
authors: SJ
authors: Glennie
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors: Kondwani C
authors: KC
authors: Jambo
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors: David
authors: D
authors: Mzinza
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Division of Clinical Sciences, University of Toronto, Ontario, Canada; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors: Oluwadamilola H
authors: OH
authors: Iwajomo
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors: Dominic
authors: D
authors: Banda
authors: Dignitas International, Zomba, Malawi.
authors: Joep J
authors: JJ
authors: van Oosterhout
authors: Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
authors: Neil
authors: N
authors: A Williams
authors: Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom.
authors: Stephen B
authors: SB
authors: Gordon
authors: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors: Robert S
authors: RS
authors: Heyderman
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D060085:Coinfection / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma; D008213:Lymphocyte Activation / Q000276:immunology; D008295:Malawi; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load
chemical_list: D023201:CD40 Ligand; D007371:Interferon-gamma