Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.
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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-? 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-? ELISpot responses (p?=?0.0040) and polyfunctional CD4+ T-cell responses (TNF-?, IL-2 and IFN-? 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.
SUBMITTER: Sepako E
PROVIDER: S-EPMC4069109 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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