Dataset Information

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-? 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

ACCESS DATA

Publications

Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.

Sepako Enoch E Glennie Sarah J SJ Jambo Kondwani C KC Mzinza David D Iwajomo Oluwadamilola H OH Banda Dominic D van Oosterhout Joep J JJ A Williams Neil N Gordon Stephen B SB Heyderman Robert S RS

PloS one 20140624 6

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 sw ...[more]

PMID: 24959834

Similar Datasets

Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Project description:BackgroundThe mitochondrial DNA (mtDNA) seems to influence in a large number of diseases, including HIV infection. Moreover, there is a substantial inter-individual variability in the CD4+ recovery in HIV-infected patients on combination antiretroviral therapy (cART). Our study aimed to analyze the association between mtDNA haplogroups and CD4+ recovery in HIV-infected patients on cART.MethodsThis is a retrospective study of 324 naïve cART patients with CD4+ <?200 cells/mm3, who were followed-up during 24 months after initiating cART. All patients had undetectable HIV viral load during the follow-up. Besides, we included 141 healthy controls. MtDNA genotyping was performed by using Sequenom's MassARRAY platform. The primary outcome variable was the slope of CD4+ recovery. Patients were stratified into two groups by the median slope value of CD4+ (9.65 CD4+ cells/mm3/month). Logistic regression analyses were performed to calculate the odds of CD4+ recovery according to mtDNA haplogroups.ResultsOur study included European HIV-infected patients within the N macro-cluster. The baseline values of CD4+ T-cells were similar between groups of patients stratified by the P50th of the slope of CD4+ T-cells recovery. Patients in the low CD4+ T-cells recovery group were older (p?=?0.001), but this variable was included in the multivariate models. When we analyzed the frequencies of mtDNA haplogroups, no significant differences between HIV-infected individuals and healthy controls were found. We did not find any significant association between mtDNA haplogroups and the slope of CD4+ T-cells recovery by linear regression analysis. However, Patients carrying haplogroup H had a higher odds of having a better CD4+ recovery (>?9.65 CD4+ cells/mm3/month) than patients without haplogroup H (p?=?0.032). The adjusted logistic regression showed that patients carrying haplogroup H had a higher likelihood of achieving a CD4+ recovery?>?9.65 CD4+ cells/mm3/month [adjusted odds ratio (aOR)?=?1.75 (95% CI?=?1.04; 2.95); p?=?0.035].ConclusionsEuropean mitochondrial haplogroup H was associated with the improved CD4+ recovery in HIV-infected patients starting cART with CD4+ <?200 cells/mm3.

Dataset Information

Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.

Publications

Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets