Title |
Incomplete Recovery of Pneumococcal CD4 T Cell Immunity after Initiation of Antiretroviral Therapy in HIV-Infected Malawian Adults
|
---|---|
Published in |
PLOS ONE, June 2014
|
DOI | 10.1371/journal.pone.0100640 |
Pubmed ID | |
Authors |
Enoch Sepako, Sarah J. Glennie, Kondwani C. Jambo, David Mzinza, Oluwadamilola H. Iwajomo, Dominic Banda, Joep J. van Oosterhout, Neil A. Williams, Stephen B. Gordon, Robert S. Heyderman |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 2% |
Denmark | 1 | 2% |
Germany | 1 | 2% |
Unknown | 58 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 20% |
Student > Ph. D. Student | 10 | 16% |
Student > Master | 5 | 8% |
Other | 4 | 7% |
Student > Postgraduate | 4 | 7% |
Other | 12 | 20% |
Unknown | 14 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 17 | 28% |
Immunology and Microbiology | 11 | 18% |
Agricultural and Biological Sciences | 6 | 10% |
Social Sciences | 3 | 5% |
Nursing and Health Professions | 2 | 3% |
Other | 7 | 11% |
Unknown | 15 | 25% |