HIV-Infected Hospitalized Patients with 2009 Pandemic Influenza A (pH1N1)—United States, Spring and Summer 2009

Peters, Philip J.; Skarbinski, Jacek; Louie, Janice K.; Jain, Seema; Roland, Michelle E.; Jani, Shilpa G.; Finelli, Lyn; Brooks, John T.

doi:10.1093/cid/ciq036

Cited by 29 publications

(35 citation statements)

References 21 publications

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“…The results of the study showed that receiving ART approximates significance in terms of being admitted to an ICU and/or death. The majority of the patients receiving ART therapy were HIV-infected patients with a CD4 cell count <200 cells/µL, while in the present study, the median value for CD4 counts was more than 600; this could explain the differences in the findings [20].…”

Section: Discussioncontrasting

confidence: 68%

Immune response to influenza A(H1N1)v in HIV-infected patients

Sansonetti

Sali

Fabbiani

et al. 2014

J Infect Dev Ctries

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Introduction: HIV infection is considered a risk factor for severe outcomes of influenza A(H1N1)v infection. However, data on immune response against influenza A(H1N1)v virus in HIV-infected patients are lacking. Methodology: Data from seven HIV-positive and 14 HIV-negative patients infected with A(H1N1)v and from 23 HIV-positive and six HIV-negative asymptomatic controls were analyzed to evaluate the clinical picture, A(H1N1)v viral shedding, and the immune response against the virus. Results: Patients displayed mainly upper respiratory tract diseases (57.1%), while pneumonia was diagnosed only in HIV-negative patients (23.8% of subjects, of which 4.8% required intensive care unit admission). At day seven, 29% of HIV-infected patients were still positive for A(H1N1)v by RT-PCR on nasopharyngeal swabs. Interestingly, a persistence of CXCL10 secretion at high level and lower IL-6 levels was observed in HIV-positive subjects. The geometric mean haemagglutination inhibition titer (HI-GMT) and anti-influenza IgM levels were lower in HIV-positive individuals while anti-influenza IgG levels remained similar in the two groups. Conclusions: The immune impairment due to HIV infection could affect A(H1N1)v clearance and could lead to a lower antibody response and a persistent secretion of CXCL10 at high levels. However, the lower IL-6 secretion and treatment with highly active antiretroviral therapy (HAART) could result in a milder clinical picture.

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Section: Discussioncontrasting

confidence: 68%

Immune response to influenza A(H1N1)v in HIV-infected patients

Sansonetti

Sali

Fabbiani

et al. 2014

J Infect Dev Ctries

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“…92 We finally included 26 zanamivir trials: 14 on treatment in adults, [71][72][73]77,[80][81][82]87,89,91,95,[97][98][99] two in children 78,84 and 10 trials in prophylaxis. 70,79,85,86,88,90,93,94,96,100 Our attempt at collecting sufficient information from regulatory files to reconstruct missing CSRs also failed because the information appeared to be insufficient for a reliable reconstruction.…”

Section: Zanamivirmentioning

confidence: 99%

“…Several of the zanamivir trials were also under-recruited. We noted the use of different relief medication across different centres within the same trial, and in one zanamivir trial, 85 according to the protocol, participants receiving antibiotics for bacterial respiratory tract infection should have been excluded but in the trial this did not happen. In the zanamivir trial, 86 the definition of 'confirmed influenza' was amended after protocol closure.…”

Section: Other Potential Sources Of Biasmentioning

confidence: 99%

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

Heneghan

Onakpoya

Jones

et al. 2016

Health Technol Assess

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BackgroundNeuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.ObjectivesTo (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu®, Roche) treatment on mortality in patients with 2009A/H1N1 influenza.MethodsWe searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators’ comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.ResultsEffect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%).Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).ConclusionsOseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.Study registrationThis study is registered as PROSPERO CRD42012002245.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…Several observational studies have shown no difference in clinical course of pH1N1 infection between HIV‐positive and HIV‐negative patients, either adults or children . On the other hand, a study of hospitalizations due to pH1N1 conducted in the US reported a disproportionately high admission rate among HIV‐positive patients, while an observational study conducted in Mexico city documented poorer outcome among HIV‐positive patients not on highly active antiretroviral treatment (HAART) and with PCR‐detectable HIV . The impact of pH1N1 infection therefore appears to be at least partially influenced by treatment and immunovirological status.…”

Section: Introductionmentioning

confidence: 99%

HIV virological suppression influences response to the AS03‐adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV‐infected children

Leahy

Goode

Lynam

et al. 2014

Influenza Resp Viruses

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DesignChildren with HIV are especially susceptible to complications from influenza infection, and effective vaccines are central to reducing disease burden in this population. We undertook a prospective, observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine in children with HIV.SettingNational referral centre for Paediatric HIV in Ireland.SampleTwenty four children with HIV were recruited consecutively and received two doses of the vaccine. The serological response was measured before each vaccine dose (Day 0 and Day 28) and 2 months after the booster dose. Antibody titres were measured using a haemagglutination inhibition (HAI) assay. Seroprotection was defined as a HAI titre ≥ 1:40; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40.Main outcome measuresThe seroconversion rates after prime and booster doses were 75% and 71%, respectively. HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate (P = 0·009), magnitude of serological response (P = 0·02) and presence of seroprotective HAI titres (P = 0·017) two months after the booster dose. No other factor was significantly associated with the seroconversion/seroprotection rate. No serious adverse effects were reported. Vaccination had no impact on HIV disease progression. The AS03-adjuvanted pandemic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children. A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression.

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HIV-Infected Hospitalized Patients with 2009 Pandemic Influenza A (pH1N1)—United States, Spring and Summer 2009

Cited by 29 publications

References 21 publications

Immune response to influenza A(H1N1)v in HIV-infected patients

Immune response to influenza A(H1N1)v in HIV-infected patients

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

HIV virological suppression influences response to the AS03‐adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV‐infected children

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