Abstract
BackgroundSeasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4+ T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART.MethodsPeripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4+ T-cell immunity.ResultsWe found lower naturally-acquired proliferative influenza-specific CD4+ T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4+ T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4+ T-cell response and reduced proportions of CD154-expressing influenza-specific CD4+ T-cells in peripheral blood.ConclusionOur data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations.
Highlights
Influenza virus causes 0.5 million deaths each year and due to the emergence of new reassortants such as the 2009 H1N1 pandemic influenza A virus, are able to escape immune surveillance, posing a major threat to global health [1]
Subjects Two cohorts of adults with no recent history of severe respiratory diseases were recruited at the Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi: a cohort of HIV-uninfected adults and asymptomatic HIV-infected individuals who were sampled once; and a cohort of HIVinfected adults about to start Highly-active antiretroviral therapy (HAART) (WHO stage 3/4) who were sampled just before starting HAART and sampled again 6months and 12months after starting HAART
The median CD4 count in HIV-uninfected adults was 602cells/ ml(531–763) and HIV-infected patients about to commence HAART was 160cells/ml(79–227) which increased to 249cells/ ml(189–360) at 6months on HAART (p,0.0001), but did not significant increase at 12months (249cells/ml(189–360) vs. 274cells/ml(197–370); p.0.05)
Summary
Influenza virus causes 0.5 million deaths each year and due to the emergence of new reassortants such as the 2009 H1N1 pandemic influenza A virus, are able to escape immune surveillance, posing a major threat to global health [1]. Most of the data on the burden of influenza infection and the characteristics of naturally-acquired immunity have emerged from Europe, North America and Southeast Asia [1]. There is conflicting data regarding HIV as one of the risk factors for more severe disease and death in influenza patients [3,4]. There has been a study from South Africa by Cohen et al that has shown that there is an increased risk of death and longer mean duration of hospitalisation amongst HIV-infected persons hospitalised with influenza-confirmed illness than HIV-uninfected counterparts [Conference paper]. We measured influenza-specific CD4+ T-cell immunity in unimmunized HIV-infected Malawian adults and investigated immune reconstitution following HAART
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