Incomplete Recovery of Pneumococcal CD4 T Cell Immunity after Initiation of Antiretroviral Therapy in HIV-Infected Malawian Adults

Sepako, Enoch, Glennie, Sarah J., Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Mzinza, David, Iwajomo, Oluwadamilola H., Banda, Dominic, van Oosterhout, Joep J., A. Williams, Neil, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 and Heyderman, Robert S. (2014) 'Incomplete Recovery of Pneumococcal CD4 T Cell Immunity after Initiation of Antiretroviral Therapy in HIV-Infected Malawian Adults'. PLoS ONE, Vol 9, Issue 6, e100640.

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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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 573 Antigens WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.2 Therapy WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0100640
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	07 Apr 2015 09:42
Last Modified:	07 Oct 2019 08:24
URI:	https://archive.lstmed.ac.uk/id/eprint/5063

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