Skip to main content

Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study)

Abstract

Introduction

Acute respiratory failure is the main reason for admission to the intensive care unit (ICU) in HIV-infected adults. There is little data about the epidemiology of respiratory viruses in this population.

Methods

HIV-infected adults admitted to two intensive care units over a 6-year period for an acute respiratory failure and explored for respiratory viruses with multiplex polymerase chain reaction (mPCR) were retrospectively selected. Objectives were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome.

Results

A total of 123 episodes were included. An HIV infection was newly diagnosed in 9% of cases and 72% of the population were on antiretroviral therapy. Real-time mPCR tests identified at least one respiratory virus in the respiratory tract of 33 (27%) patients, but with a non-viral copathogen in two-thirds of cases. Rhinovirus was predominant, documented in 15 patients, followed by Influenza and Respiratory Syncytial Viruses (both n = 6). The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL (n = 13 (20%) vs. n = 2 (4%), p < 0.01). In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis.

Conclusions

Viruses are frequently identified in the respiratory tract of HIV-infected patients with acute respiratory failure that requires ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.

Introduction

Acute respiratory failure (ARF) is the leading cause of admission to the intensive care unit (ICU) in HIV-infected patients [1,2,3]. Infectious causes are predominant, although the proportion of opportunistic infections has decreased significantly in the era of combination antiretroviral therapy (ART) [2, 4, 5]. In contrast, the burden of non-HIV-related pulmonary events, such as bacterial pneumonia, acute bronchitis and acute exacerbation of chronic obstructive pulmonary disease (COPD) has been shown increasing [2, 3, 6]. These important changes in the etiologic panel of ARF in HIV-infected patients question the role of respiratory viruses. Indeed, using nucleic acid amplification test such as multiplex polymerase chain reaction (mPCR), these pathogens have been shown highly prevalent (20–56%) in large cohorts of adult patients admitted to the ICU for all-cause ARF [7, 8], community-acquired pneumonia [9, 10], hospital-acquired pneumonia [11], acute exacerbation of COPD [12, 13], and asthma [14], compared to asymptomatic adults [15, 16]. High prevalence has also been described in specific immunocompromised populations, such as cancer and hematology patients [17, 18]. In contrast, little is known about the epidemiology of respiratory viruses in HIV-infected patients [19, 20], especially those admitted to the ICU, and the prevalence of respiratory viruses according to the CD4 T-cell deficiency. Moreover, coinfections with virus and opportunistic pathogens may occur. Overall, respiratory virus-associated infections may affect prognosis.

Therefore, we conducted a comprehensive observational study among adult HIV-infected ICU patients with ARF explored with respiratory mPCR. Our goals were to describe the prevalence of respiratory viruses, coinfections with non-viral pathogens, and hospital outcome.

Methods

Study design and patient selection

We conducted a retrospective bicenter observational study in two ICU of the Paris area (the 26-bed ICU of the Bichat University Hospital and the 20-bed ICU of the Tenon University Hospital). From April 2011 to April 2017, all consecutive HIV-infected patients admitted to ICU having undergone an mPCR in the respiratory tract within 72 h following their ICU admission were screened. Medical records were independently reviewed by two physicians (AE and GV). All patients with ARF at ICU admission were included. ARF was defined by the presence of at least two of the following criteria: cough, expectoration, dyspnea, rales, signs of respiratory distress (tachypnea exceeding 30/min, paradoxical abdominal breathing), chest pain, hypoxemia requiring oxygen therapy, noninvasive ventilation or intubation. In case of multiple admissions over the 6-year study period, only the first admission was analyzed.

Data collection

At ICU admission and during ICU stay, data regarding demographics, comorbidity, HIV-related characteristics, clinical examinations, laboratory and radiological findings, microbiologic investigations, and therapeutic management were collected (for details, see Additional file 1). Mortality was defined as death from any cause within 28 days following the ICU admission.

Microbiological evaluation

Respiratory mPCRs were performed either in nasopharyngeal (NP) swabs or in lower respiratory tract (LRT) specimen, usually bronchoalveolar lavage (BAL) fluid otherwise endotracheal aspirate. During the study period, different respiratory mPCR kits (Additional file 1: Table S1) were used (for more details about microbiological evaluation, see Additional file 1).

Classification of patients according to the causative diagnosis of ARF

Medical charts were independently reviewed by two clinicians (AE and GV). They determined the causative diagnosis of ARF for each patient, using a 5-class classification. In case of an inter-reviewer discordance, a shared review of the medical charts was performed, and an agreement was found. The five mutually exclusive classes of causative diagnosis for ARF were: (i) Pneumocystis jirovecii pneumonia (PCP); (ii) other opportunistic lung infections; (iii) non-opportunistic acute lung infection; (iv) non-infectious lung disease, and (v) extra-pulmonary cause (for details, see Additional file 1).

Endpoints

The primary endpoint was to determine the prevalence of respiratory viruses according to the CD4 lymphocyte count. A respiratory virus documented with mPCR was always considered as a pathogen of the respiratory tract, regardless of the type of specimen (NP or LRT). The CD4 lymphocyte count measured during the ICU stay was used to group patients, with a cut-off of 200 cells/µL (≤ 200 cells/µL for the Low-CD4 group; > 200 cells/µL for the High-CD4 group) [19, 21].

Secondary endpoints were to describe the epidemiology of respiratory viruses and coinfections with non-viral pathogens, to identify risk factors for respiratory virus-associated infection, and to study outcome. A composite criterion named “complicated course” included death from any cause within 28 days following the ICU admission or mechanical ventilation for more than 7 days.

Data presentation and statistical analysis

Continuous data were expressed as median [first through third quartiles] and were compared using the pairwise Mann and Whitney test. Categorical data were expressed as number (percentage) and were evaluated using the chi-square test or Fisher exact test. p values less than 0.05 were considered significant. A univariate logistic regression with clinically relevant variables was used to identify variables associated with a respiratory virus-associated infection. A multivariate conditional logistic regression, including variables with p value less than 0.10 in the previous step, was used to identify variables independently associated with a respiratory virus-associated infection. Similar statistical analyses were performed to identify variables independently associated with death from any cause within 28 days following the ICU admission and mechanical ventilation for more than 7 days in survivors at Day-28. Quantitative variables that did not validate the log-linearity assumption were transformed into categorical variables according to their median value. Missing data were imputed to the median or the more frequent value. The accuracy of the final model was tested using area under the receiver operating characteristic curve analysis and the Hosmer–Lemeshow chi-square test. Analyses were performed using the SAS software package (SAS Institute, Cary, NC, USA).

Ethical considerations

This study was approved by the institutional review board of the French Society of Respiratory Diseases (Reference CEPRO 2018-017) according to the French regulations. The board waived the need for signing consent for patients included in the study.

Results

Population

During the 6-year study period, 135 HIV-infected adult patients were admitted at least once to ICU and underwent a respiratory mPCR in the first 72 h of the ICU stay. Among them, 12 did not fulfill criteria of ARF. The final study group consisted of 123 patients. Their main characteristics, stratified by the CD4 lymphocyte count at ICU admission, are presented in Table 1. Of these 123 patients, 2 were admitted twice during the study period and one was admitted thrice. Eleven patients (9%) were newly diagnosed as having HIV infection on ICU admission; the remaining 112 had been previously diagnosed, and 88 were on ART but with poor adherence to the treatment in 21 patients, as mentioned by the infectiologist in the medical charts. Latest available median CD4 lymphocyte count and HIV viral load were 351 cells/µL [140–600] and 0 log copies/mL [0–3.4], respectively. At least one additional factor of immunosuppression was identified in 10 (8%) patients.

Table 1 Baseline characteristics, behavior during ICU stay, and outcome of 123 HIV-infected patients admitted to the ICU for acute respiratory failure, according to the CD4 lymphocyte count on the ICU admission

At ICU admission, median CD4 lymphocyte count was 170 cells/µL [20–430], with 66 patients (54%) equal or below 200 cells/µL (Low-CD4 group) and 57 (46%) above 200 cells/µL (High-CD4 group). Both these groups did not differ regarding demographics, performance status, factors of immunosuppression other than HIV and comorbidity, except for COPD which was more prevalent in the High-CD4 group (n = 12 (21%) vs. n = 4 (6%), p = 0.01).

Microbiological investigations

The microbiological investigations are displayed in Additional file 1: Table S2. mPCR was performed in NP swabs exclusively (n = 46, 37%) or in LRT specimen exclusively (n = 50, 41%), or both (n = 27, 22%). Respiratory tract specimens for bacterial culture have been obtained in 110 (91%) patients. BAL fluid has been obtained in 77 (63%) patients.

Causative diagnosis of ARF

Causative diagnoses of ARF are displayed in Table 2. An opportunistic lung infection was diagnosed in 38 (31%) patients. Seven of the 11 patients with newly diagnosed HIV infection and 8 patients receiving ART, but with a poor adherence to the treatment had PCP.

Table 2 Causative diagnosis of acute respiratory failure in 123 HIV-infected patients admitted to the ICU

Non-opportunistic acute lung infections were identified as causative diagnosis of ARF in 59 (48%) patients. All the bacteria-infected patients received an appropriate antimicrobial regimen within the first 24 h of ICU stay. Eight patients had a clinical presentation suggestive of lung infection, but without microbiological documentation.

The ARF was attributed to a non-infectious lung disease in 19 (15%) patients, mainly related to a decompensated chronic condition, i.e., acute exacerbation of COPD and pulmonary edema.

Analysis according to the viral diagnosis

Overall, 36 respiratory viruses were identified in 33 (27%) patients (Table 3). Rhinovirus was predominant (n = 15), followed by Influenza (n = 6), Respiratory Syncytial Virus (n = 6) and Parainfluenza Virus (n = 5). Only one pure virus–virus coinfection was found.

Table 3 Description of respiratory virus-associated infections and coinfections with non-viral pathogens

The prevalence of respiratory virus-associated infection did not differ among Low- and High-CD4 groups (Table 1); therefore, the median CD4 lymphocyte count in respiratory virus-infected patients was 109 [16–420] cells/µL, in comparison with 192 [27–428] cells/µL in non-infected patients (Fig. 1). However, the prevalence of Rhinovirus-associated infection was higher in the Low-CD4 group, and three-quarters of Rhinovirus-infected patients exhibited a CD4 lymphocyte count below 200 cells/µL (Fig. 2).

Fig. 1
figure1

Diagnosis of respiratory virus-associated infection according to the CD4 lymphocyte count on the ICU admission

Fig. 2
figure2

Diagnosis of Rhinovirus-associated infection according to the CD4 lymphocyte count on the ICU admission

In 22 patients, the viral documentation was accompanied by a non-viral documentation (Additional file 1: Figure S1), with bacteria–virus coinfection in 11 patients, bacteria–virus–virus in 2 patients, P. jirovecii–virus in 7 patients and P. jirovecii–virus–virus in one patient.

The rate of viral documentation among patients explored with NP swab exclusively, LRT specimen exclusively, or both, did not differ significantly (30%, 26% and 22%, respectively; p = 0.73).

Documentation of respiratory viruses was more frequent during the winter period (October to March) (Additional file 1: Figure S2). Conversely, Rhinovirus documentation did not follow a seasonal distribution, since only 7/15 were observed during the period from October to March.

Characteristics of the population, stratified by respiratory virus-associated infection are presented in Additional file 1: Table S3. At ICU admission, respiratory virus-infected patients displayed higher respiratory rate and fever. In multivariate analysis, female gender, smoking and steroid therapy were shown as independently associated with respiratory virus-associated infection (Table 4).

Table 4 Multivariate analysis of the risk factors for respiratory virus-associated infection in 123 HIV-infected patients admitted to the ICU for acute respiratory failure

Outcome

Mortality at Day-28 was 12%, and 26% of patients displayed a complicated course, without difference between High-CD4 and Low-CD4 groups (Table 1). We investigated whether a respiratory virus-associated infection affected prognosis. In the analysis stratified by respiratory virus-associated infection, outcome was similar between infected and non-infected patients (Additional file 1: Table S3). In multivariate analysis, a respiratory virus-associated infection was not identified as an independent factor of either a complicated course (Table 5) or death at Day-28 (Additional file 1: Table S4).

Table 5 Multivariate analysis of the risk factors for complicated course in 123 HIV-infected patients admitted to the ICU for acute respiratory failure

Discussion

This retrospective study investigated the epidemiology of respiratory viruses in HIV-infected adults admitted to the ICU for ARF. Real-time mPCR tests identified at least one virus in the respiratory tract of 27% of patients, but with a non-viral copathogen in two-thirds of cases. The prevalence of respiratory virus-associated infection did not vary along with the level of the CD4 T-cell deficiency, except for Rhinovirus which was more prevalent in patients with a CD4 lymphocyte count below 200 cells/µL. In multivariate analysis, respiratory virus-associated infection was not associated with a worse prognosis.

In this study, more than one patient out of four (27%) were infected with at least one respiratory virus. This finding illustrated the high yield of an aggressive diagnostic strategy with a broad panel mPCR on respiratory tract specimens. Our results are original since prior works having described the etiological panel of ARF in HIV-infected ICU patients were conducted before the era of real-time mPCR [2, 4, 22]. Interestingly, the rate of viral documentation that we observed was similar to what had been described (27 to 29%) previously in non-HIV adults admitted to the ICU for an acute respiratory disorder requiring intubation [7, 8].

We identified at least one non-viral copathogen in more than two-thirds of the patients with a viral documentation, in line with a recent report in a population with a high prevalence of tuberculosis [19, 23]. Non-opportunistic acute lung infections, including pneumonia, acute bronchitis and exacerbation of COPD, were the first cause of ARF, consistent with previous reports in Western countries [2, 4]. This finding highlights the burden of chronic respiratory conditions in aging HIV-infected populations [6]. Here, more than 40% of patients were smokers. Synergistic effects of tobacco and HIV [24] in promoting chronic bronchitis and pro-COPD changes in the lung [25] have been demonstrated. Moreover, high rates of viral documentation within airways of COPD patients both at stable state and during exacerbation have been reported [26]. These data may explain the high rate of viral documentation that we observed. In multivariate analysis, smoking was independently associated with respiratory virus-associated infection. This finding is in line with previous works demonstrating that tobacco exposure alters immune responses to Rhinovirus [27], Influenza Virus [28] and Respiratory Syncytial Virus [29]. Interestingly, female gender was associated with an increased risk of respiratory virus-associated infection on multivariate analysis. Prior cohort studies in primary care described an increased risk for development of Influenza-like illnesses in women compared to men [30, 31]. However, to our knowledge, no prior study has specifically explored this point in HIV-infected populations admitted for ARF.

In this study, we also aimed to investigate a putative role of the HIV-related CD4 T-cell deficiency in promoting respiratory virus-associated infection. Previous studies explored this point in children, but with conflicting results. Annamalay et al. described similar rates of viral documentation in HIV-infected and non-infected children admitted for lower respiratory tract infections [32], whereas O’Callaghan-Gordo et al. observed that respiratory virus-associated infections were 6 to 16 times more prevalent among HIV-infected children admitted for pneumonia [33]. As we did not include a comparative non-HIV population, we rather examined whether or not the rate of viral documentation varied along with the level of CD4 T-cell deficiency. Finally, we found no association between the CD4 lymphocyte count and the risk of respiratory virus-associated infection, in line with a previous report focusing on Influenza viruses [34].

Rhinovirus was the predominant virus, accounting for more than 40% of viral documentations. This high prevalence was consistent with that of previous reports in ICU patients with ARF [7], community-acquired pneumonia [35] or acute exacerbation of COPD [13]. Surprisingly, Rhinovirus was much more prevalent in low-CD4 patients. This finding is original, since no prior work has specifically explored this point in adults. In HIV-infected children, Rhinovirus has been shown highly prevalent, during both pneumonia and bronchiolitis, but without data regarding a putative association with the level of CD4 T-cell deficiency [32, 36]. Other data in hematology and cancer adults demonstrated high rates of Rhinovirus documentation within airways during respiratory tract infections [37, 38]. To explain this high prevalence in immunocompromised patients, a mechanism of prolonged viral shedding has been proposed, rather than iterative reinfections as observed in COPD patients [39]. The prolonged Rhinovirus shedding may be attributable to an inefficient immunological control of a single infectious episode [40, 41]. Therefore, in pediatric hematopoietic stem cell transplant recipients with a persistent Rhinovirus shedding (≥ 30 days), Piralla et al. demonstrated significant lower CD4, CD8 and NK lymphocyte counts at the onset of infection, as compared to children with a brief Rhinovirus shedding. Moreover, a decrease in Rhinovirus load was associated with significant increases of the same lymphocyte counts [42]. These data would suggest an important role for the T-cell immunity in the control of Rhinovirus infection, and subsequently, may explain a delayed Rhinovirus clearance in low-CD4 HIV-infected patients, resulting in persistent shedding and increased prevalence.

We observed a high rate of dual infection, either virus–bacteria or virus–opportunistic pathogen. These findings made us consider the prognostic impact of such coinfections. Studies in ICU adult patients with pneumonia suggested that virus–bacteria coinfection was associated with a worse prognosis [43]. In mice, the coinfection of Influenza with Streptococcus pneumoniae [44], Legionella pneumophila [45] or Staphylococcus aureus [46] impaired the anti-Influenza immune response and increased mortality. Whether similar synergistic effects exist in virus–opportunistic pathogen coinfection remain unknown. Only one animal study has explored the couple Pneumocystis jirovecii–Influenza, but in a successive rather than concomitant model [47]. Unfortunately, in our study, the low number of observations prevented us from analyzing the prognosis according to the presence of coinfections.

Our study has several limitations. First, this study included adult patients with ARF that required ICU admission, preventing any conclusion on other populations such as HIV-infected children or HIV-infected adults with ARF that did not require ICU admission. Second, the study was retrospective, so we did not control the microbiological investigations. The preferred sample for mPCR test in non-intubated patients was not the sputum, but the nasopharyngeal swab [48]. Several factors may have discouraged clinicians to use sputum, including the high number of patients unable to produce sputum [49] and the highly viscous nature of this sample that can make nucleic acid extraction difficult [50]. By definition, an mPCR was performed in the respiratory tract of every included patient because it was a criterion for patient screening. But some other microbiological tests were only occasionally performed, i.e., cytomegalovirus PCR. Furthermore, the retrospective design prevented us from obtaining a number of data, which were rarely reported in medical records by physicians, including vaccine history, Pneumocystis jirovecii prophylaxis, symptoms before hospital referral, and duration of symptoms before ICU admission. Third, only patients having undergone an mPCR in the respiratory tract within the 72 h following their ICU admission were screened; this might suggest a confounding of indication. Fourth, the choice to classify patients according to their CD4 lymphocyte count on the ICU admission, instead of the latest known value, might be criticized. However, this choice was guided by the high number of missing values in the latest CD4 lymphocyte count as well as the number of newly diagnosed patients without any prior CD4 lymphocyte count. Fifth, we assumed that a virus identified with PCR in nasopharyngeal or lower respiratory tract samples was always a pathogen of the respiratory tract, whatever the clinical picture and radiological features. This might be criticized since respiratory viruses might be present in asymptomatic adult subjects [15], even if it seems rare, about 2% of asymptomatic adults seen at the emergency department [16]. Sixth, to avoid overinterpreting the data, we decided to consider respiratory viruses as a homogeneous group of pathogens in the analysis stratified by respiratory virus-associated infection. This might be criticized since the pathogenicity differs from one viral species to another.

Conclusions

Viruses are frequently identified in the respiratory tract of HIV-infected patients with ARF that required ICU admission, but with a non-viral copathogen in two-thirds of cases. Rhinovirus is the predominant viral specie; its prevalence is highest in patients with a CD4 lymphocyte count below 200 cells/µL.

Availability of data and materials

Data and materials supporting the findings of this study can be entirely shared if asked.

Abbreviations

ARF:

Acute respiratory failure

BAL:

Bronchoalveolar lavage

CMV:

Cytomegalovirus

COPD:

Chronic obstructive pulmonary disease

ESM:

Electronic supplementary material

HIV:

Human immunodeficiency virus

ICU:

Intensive care unit

LRT:

Low respiratory tract

mPCR:

Multiple polymerase chain reaction

NP:

NasoPharyngeal

PCP:

Pneumocystis jirovecii pneumonia

SAPS II:

Simplified Acute Physiology Score

SOFA:

Sepsis-related Organ Failure Assessment

WHO:

World Health Organization

References

  1. 1.

    Chiang H-H, et al. Admissions to intensive care unit of HIV-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors. Crit Care. 2011;15:R202.

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Barbier F, et al. Etiologies and outcome of acute respiratory failure in HIV-infected patients. Intensive Care Med. 2009;35:1678–86.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Barbier F, et al. Temporal trends in critical events complicating HIV infection: 1999–2010 multicentre cohort study in France. Intensive Care Med. 2014;40:1906–15.

    PubMed  Google Scholar 

  4. 4.

    Powell K, et al. Survival for patients with HIV admitted to the ICU continues to improve in the current era of combination antiretroviral therapy. Chest. 2009;135:11–7.

    PubMed  Google Scholar 

  5. 5.

    Benito N, Moreno A, Miro JM, Torres A. Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012;39:730–45.

    CAS  PubMed  Google Scholar 

  6. 6.

    Crothers K, et al. HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med. 2011;183:388–95.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Daubin C, et al. Epidemiology and clinical outcome of virus-positive respiratory samples in ventilated patients: a prospective cohort study. Crit Care. 2006;10:R142.

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    van Someren Gréve F, et al. Respiratory viruses in invasively ventilated critically ill patients—a prospective multicenter observational study. Crit Care Med. 2018;46:29–36.

    Google Scholar 

  9. 9.

    Voiriot G, et al. Viral-bacterial coinfection affects the presentation and alters the prognosis of severe community-acquired pneumonia. Crit Care. 2016;20:375.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Karhu J, Ala-Kokko TI, Vuorinen T, Ohtonen P, Syrjälä H. Lower respiratory tract virus findings in mechanically ventilated patients with severe community-acquired pneumonia. Clin Infect Dis. 2014;59:62–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Loubet P, et al. Impact of respiratory viruses in hospital-acquired pneumonia in the intensive care unit: a single-center retrospective study. J Clin Virol. 2017;91:52–7.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Cameron RJ, et al. Virus infection in exacerbations of chronic obstructive pulmonary disease requiring ventilation. Intensive Care Med. 2006;32:1022–9.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Daubin C, et al. Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study. Intensive Care Med. 2018;44:428–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Tan WC, et al. Epidemiology of respiratory viruses in patients hospitalized with near-fatal asthma, acute exacerbations of asthma, or chronic obstructive pulmonary disease. Am J Med. 2003;115:272–7.

    PubMed  Google Scholar 

  15. 15.

    Byington CL, et al. Community surveillance of respiratory viruses among families in the utah better identification of germs-longitudinal viral epidemiology (BIG-LoVE) study. Clin Infect Dis. 2015;61:1217–24.

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Jain S, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Legoff J, et al. Clinical significance of upper airway virus detection in critically ill hematology patients. Am J Respir Crit Care Med. 2019;199:518–28.

    PubMed  Google Scholar 

  18. 18.

    Chemaly RF, Shah DP, Boeckh MJ. Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies. Clin Infect Dis. 2014;59(Suppl 5):S344–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Figueiredo-Mello C, Naucler P, Negra MD, Levin AS. Prospective etiological investigation of community-acquired pulmonary infections in hospitalized people living with HIV. Medicine (Baltimore). 2017;96:e5778.

    Google Scholar 

  20. 20.

    Garbino J, Inoubli S, Mossdorf E, Weber R, Tamm M, Soccal P, Aubert JD, Bridevaux PO, Tapparel C, Kaiser L, Swiss HIV Cohort Study. Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection. AIDS. 2008;22(6):701–5.

    PubMed  Google Scholar 

  21. 21.

    Khouli H, Afrasiabi A, Shibli M, Hajal R, Barrett CR, Homel P. Outcome of critically ill human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. J Intensive Care Med. 2005;20(6):327–33.

    PubMed  Google Scholar 

  22. 22.

    Dickson SJ, et al. Survival of HIV-infected patients in the intensive care unit in the era of highly active antiretroviral therapy. Thorax. 2007;62:964–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Maartens G, Griesel R, Dube F, Nicol M, Mendelson M. Etiology of pulmonary infections in human immunodeficiency virus-infected inpatients using sputum multiplex real-time polymerase chain reaction. Clin Infect Dis. 2019. https://doi.org/10.1093/cid/ciz332.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Rossouw TM, Anderson R, Feldman C. Impact of HIV infection and smoking on lung immunity and related disorders. Eur Respir J. 2015;46:1781–95.

    CAS  PubMed  Google Scholar 

  25. 25.

    Chand HS, et al. Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques. J Clin Invest. 2018;128:5428–33.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Wilkinson TMA, et al. A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD. Thorax. 2017;72:919–27.

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Eddleston J, Lee RU, Doerner AM, Herschbach J, Zuraw BL. Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection. Am J Respir Cell Mol Biol. 2011;44:118–26.

    CAS  PubMed  Google Scholar 

  28. 28.

    Wu W, et al. Cigarette smoke attenuates the RIG-I-initiated innate antiviral response to influenza infection in two murine models. Am J Physiol Lung Cell Mol Physiol. 2014;307:L848–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Castro SM, Chakraborty K, Guerrero-Plata A. Cigarette smoke suppresses TLR-7 stimulation in response to virus infection in plasmacytoid dendritic cells. Toxicol In Vitro BIBRA. 2011;25:1106–13.

    CAS  Google Scholar 

  30. 30.

    Hardelid P, Rait G, Gilbert R, Petersen I. Recording of influenza-like illness in UK primary care 1995–2013: cohort study. PLoS ONE. 2015;10:e0138659.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Adler AJ, Eames KTD, Funk S, Edmunds WJ. Incidence and risk factors for influenza-like-illness in the UK: online surveillance using Flusurvey. BMC Infect Dis. 2014;14:232.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Annamalay AA, et al. Respiratory viruses in young South African children with acute lower respiratory infections and interactions with HIV. J Clin Virol. 2016;81:58–63.

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    O’Callaghan-Gordo C, et al. Etiology and epidemiology of viral pneumonia among hospitalized children in rural Mozambique: a malaria endemic area with high prevalence of human immunodeficiency virus. Pediatr Infect Dis J. 2011;30:39–44.

    PubMed  Google Scholar 

  34. 34.

    Kok J, et al. Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected individuals. J Acquir Immune Defic Syndr. 2011;1999(56):91–4.

    Google Scholar 

  35. 35.

    Wiemken T, et al. Incidence of respiratory viruses in patients with community-acquired pneumonia admitted to the intensive care unit: results from the Severe Influenza Pneumonia Surveillance (SIPS) project. Eur J Clin Microbiol Infect Dis. 2013;32:705–10.

    CAS  PubMed  Google Scholar 

  36. 36.

    Nunes MC, et al. Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV-infected and HIV-uninfected South African children. PLoS ONE. 2014;9:e86448.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Hammond SP, et al. Respiratory virus detection in immunocompromised patients with FilmArray respiratory panel compared to conventional methods. J Clin Microbiol. 2012;50:3216–21.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Camps Serra M, et al. Virological diagnosis in community-acquired pneumonia in immunocompromised patients. Eur Respir J. 2008;31:618–24.

    Google Scholar 

  39. 39.

    Zlateva KT, et al. Prolonged shedding of rhinovirus and re-infection in adults with respiratory tract illness. Eur Respir J. 2014;44:169–77.

    PubMed  Google Scholar 

  40. 40.

    Kaiser L, et al. Chronic rhinoviral infection in lung transplant recipients. Am J Respir Crit Care Med. 2006;174:1392–9.

    PubMed  Google Scholar 

  41. 41.

    Pathak AK, Adams RH, Shah NC, Gustin KE. Persistent human rhinovirus type C infection of the lower respiratory tract in a pediatric cord blood transplant recipient. Bone Marrow Transplant. 2013;48:747–8.

    CAS  PubMed  Google Scholar 

  42. 42.

    Piralla A, et al. Persistent rhinovirus infection in pediatric hematopoietic stem cell transplant recipients with impaired cellular immunity. J Clin Virol. 2015;67:38–42.

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Burk M, El-Kersh K, Saad M, Wiemken T, Ramirez J, Cavallazzi R. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis. Eur Respir Rev. 2016;25(140):178–88.

    PubMed  Google Scholar 

  44. 44.

    Blevins LK, Wren JT, Holbrook BC, Hayward SL, Swords WE, Parks GD, Alexander-Miller MA. Coinfection with Streptococcus pneumoniae negatively modulates the size and composition of the ongoing influenza-specific CD8+ T cell response. J Immunol. 2014;193(10):5076–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ, Decker T, Medzhitov R. Role of tissue protection in lethal respiratory viral-bacterial coinfection. Science. 2013;340(6137):1230–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Iverson AR, Boyd KL, McAuley JL, Plano LR, Hart ME, McCullers JA. Influenza virus primes mice for pneumonia from Staphylococcus aureus. J Infect Dis. 2011;203(6):880–8.

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Wiley JA, Harmsen AG. Pneumocystis infection enhances antibody-mediated resistance to a subsequent influenza infection. J Immunol. 2008;180(8):5613–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Philippot Q, Labbé V, Pichon J, Djibré M, Fartoukh M, Voiriot G. Diagnosis and management of respiratory viruses in critically ill adult patients: an international survey of knowledge and practice among intensivists. Ann Intensive Care. 2020;10(1):50.

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Musher DM, Montoya R, Wanahita A. Diagnostic value of microscopic examination of Gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia. Clin Infect Dis. 2004;39(2):165–9.

    PubMed  Google Scholar 

  50. 50.

    Jeong JH, Kim KH, Jeong SH, Park JW, Lee SM, Seo YH. Comparison of sputum and nasopharyngeal swabs for detection of respiratory viruses. J Med Virol. 2014;86(12):2122–7.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Affiliations

Authors

Contributions

GV had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. AE participated in the design of the study, participated in the data acquisition, analysis and interpretation, and the statistical analysis, and drafted the manuscript. JP, BV, AS, LB, QP, JP and VL participated in the data acquisition, analysis and interpretation, and helped to revise the manuscript. RS participated in the data analysis and interpretation, and the statistical analysis. MF and JFT participated in the design of the study, participated in the data analysis and interpretation, and helped to revise the manuscript. GV designed the study, participated in the data analysis and interpretation, and the statistical analysis, and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Guillaume Voiriot.

Ethics declarations

Consent for publication

Not applicable.

Competing interests

The authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Additional file 1.

 Additional information on Material and methods, Table S1 (Panels of mPCR kits used in the two participating ICUs over the 6-year study period), Table S2 (Microbiological investigations performed in 123 HIV-infected patients admitted to the ICU for acute respiratory failure, according to the diagnosis of respiratory virus-associated infection), Table S3 (Baseline characteristics, behavior during ICU stay, and outcome of 123 HIV-infected patients admitted to the ICU for acute respiratory failure, according to the diagnosis of respiratory virus-associated infection), Table S4 (Multivariate analysis of the risk factors for death at Day-28 in 123 HIV-infected patients admitted to the ICU for acute respiratory failure), Figure S1 (Distribution of the microbiological documentations in 123 HIV-infected patients admitted to the ICU for acute respiratory failure), Figure S2 (Seasonal distribution of viral documentations).

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Elabbadi, A., Pichon, J., Visseaux, B. et al. Respiratory virus-associated infections in HIV-infected adults admitted to the intensive care unit for acute respiratory failure: a 6-year bicenter retrospective study (HIV-VIR study). Ann. Intensive Care 10, 123 (2020). https://doi.org/10.1186/s13613-020-00738-9

Download citation

Keywords

  • Acute respiratory failure
  • Human immunodeficiency virus
  • Polymerase chain reaction
  • Viral pneumonia
  • Viral pneumonia