aDepartment of Medicine, School of Medicine, Pontificia Universidad Católica de Chile
bDepartment of Medicine, Hospital San Juan de Dios y Clínica Dávila, Chile
cDepartment of Medicine, Hospital Sótero del Río, Chile
dDepartment of Medicine, Hospital FACH, Santiago, Chile.
Received 12 March, 2010
Revised 11 July, 2010
Accepted 21 July, 2010
Correspondence to Carlos M. Perez, MD, Department of Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 357, Santiago, Chile. E-mail: email@example.com
Objective: To characterize the clinical presentation, course and mortality of pandemic influenza in HIV-1-infected patients in Santiago, Chile.
Methods: Prospective observational study.
Results: Thirty patients were included (three hospitalized), 93% were on HAART, mean CD4+ cell count was 423 cells/μl and viral load was undetectable in 77% of patients. All patients had fever, 90% had cough, 80% had myalgias, 70% had pharyngeal congestion, 47% had coryza, 47% had odynophagia, 37% had headache and 23% had vomiting. Four patients developed pneumonia. All patients received antiviral therapy and no patient died.
Conclusions: HIV patients infected by the new influenza A pandemic (H1N1) virus behave similarly to the general population.
Influenza A pandemic (H1N1) virus has spread world wide since March 2009. Clinical manifestations range from mild and self-limited illness to catastrophic respiratory failure [1–5]. In Chile, during 2009, a total of 368 118 clinical cases were reported, 12 302 of which were confirmed by specific PCR. The epidemic began in May 2009 and ended in August 2009 . The rate of severe acute respiratory infection was 9.6 per 100 000 inhabitants, with 0.9 deaths per 100 000 inhabitants (150 deaths, of which 70.6% had some underlying illness) . By that time, 99% of the circulating viruses corresponded to influenza A pandemic (H1N1) virus; therefore, the diagnosis was made in the majority of cases according to clinical criteria [5,6]. Little has been reported on the impact of this new virus in HIV-1-infected patients [7–9].
Patients and methods
In a prospective, observational study, we characterized the clinical presentation, course, predictors of severity and mortality of influenza A pandemic (H1N1) in HIV-1-infected patients in Santiago, Chile, during the 2009 Chilean influenza pandemic. We included patients with HIV-1 infection and clinical diagnosis of pandemic influenza according to the Chilean guidelines . Patients were seen between June and August 2009 in six public or private institutions participating in the study (Hospital Clínico Universidad Católica, Clínica UC San Carlos, Hospital Sótero del Río, Hospital San Juan de Dios, Hospital FACH y Clínica Dávila).
A total of 1720 patients with HIV-1 infection were seen in the period between June and August 2009, 30 of whom were infected with influenza A pandemic (H1N1) and were included in the study (incidence 1.74%). The diagnosis was made clinically in 25 patients and confirmed by PCR in five. Three patients were hospitalized and had PCR-confirmed pandemic influenza. Twenty-three patients were men, mean age was 35 years and range 21–66 years. Five out of 30 patients had comorbidities (two had diabetes mellitus type 2, two were obese and one had hypertension). Nine patients were smokers. One patient was pregnant at the time of the infection. Twenty-four patients had less than 10 years since diagnosis of HIV infection. Twenty-eight patients were on HAART. The most common antiretroviral regimen was the combination of zidovudine/lamivudine and efavirenz (33.3%). The mean last lymphocyte CD4+ cell count prior to influenza infection was 423 cells/μl, range 95–771 cells/μl. Only two patients in the study had CD4+ cell counts below 200 cells/μl (one had <100 cells/μl). The HIV-1 viral load was undetectable in the 76.7% of the cases (23 patients). Eleven patients (37%) had received 2009 seasonal influenza vaccine.
The average interval between beginning of symptoms of influenza and first medical visit was 2.6 days, with a range between 1 and 8 days. All patients had fever, with a mean duration of 2.6 days. Thirty percent (nine patients) had chills and 80% (24 patients) had myalgias. Cough was present in 90% (28 patients), coryza in 46.7% (20 patients), odynophagia in 46.7% (14 patients) and dyspnea in 10% (four patients). Thirty-seven percent (11 patients) experienced headache. Four patients (13.3%) had diarrhea and seven (23.3%) had vomiting. On physical examination, it was observed that pharyngeal congestion was present in 70% (21 patients), pulmonary crackles in 20% (seven patients) and bronchial obstruction in three (10%) patients. Only one patient presented with tachypnea. In 12 patients, a chest radiograph was performed, showing a new lung infiltrate consistent with pneumonia in four of them (two were hospitalized). One patient developed acute sinusitis.
Among admitted patients, only one individual required oxygen support and none of them underwent mechanical ventilation. The average hospital stay was 3 days. It should be noted that hospitalized patients had an average CD4+ cell count of 506 cells/μl, undetectable viral load and had all been vaccinated for seasonal influenza.
Following Chilean guidelines, all patients received antiviral therapy, 29 patients with oseltamivir and one patient with zanamivir (the pregnant woman). The disease lasted an average of 5.6 days and no patient died.
There are few reports in the world literature on influenza in HIV-infected patients, but given the status of immunodeficiency, we can assume that these patients would have more serious complications and possibly more deaths. The Centers for Disease Control and Prevention (CDC), suggested that people carrying HIV, mainly those with low CD4+ cell count or AIDS, experience more severe complications by seasonal influenza, and, therefore, the same may occur with pandemic influenza [7,9]. The symptoms of influenza in HIV-1-infected individuals may be atypical and for patients with low CD4+ cell count, the infection may progress rapidly, leading to severe complications such as viral or bacterial pneumonia [8,9].
In our study, the clinical presentation was similar to what has already been described for the general population with seasonal influenza. Even when the diagnosis of Influenza A pandemic (H1N1) was established clinically in the majority of patients, when a specific test was performed, the infection was always confirmed. Moreover, during the time we recruited the patients, almost 100% of the patients with influenza-like symptoms in Chile had Influenza A pandemic (H1N1) . No patient had severe respiratory insufficiency and only three patients were hospitalized, one of them requiring supplementary oxygen. The majority of patients in this study had undetectable HIV-1 viral load and only one had CD4+ cell count less than 100 cells/μl. This could explain their behavior with regards to prognosis and mortality, similar to general population. It was also noted that the time between the onset of symptoms and the first consultation was 2.6 days, similar to what has been described for nonimmunocompromised persons in Chile . This eliminates a possible bias for this study.
Despite a small number of recruited patients, the incidence in our population (1.74%) was similar to the estimated incidence in the Chilean population during the pandemic (2.1%). We conclude that HIV-1-infected patients infected by the new Influenza A pandemic (H1N1) virus seen in these five centers behave similarly to the general population, both in clinical presentation and outcome, and there is not a direct relationship between detectable viral load or low number of CD4+ cells and risk for hospitalization or complications. However, new prospective studies are required to support these data.
The authors thank the Department of Medicine, Pontificia Universidad Católica de Chile for the financial support provided.
3. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360:2605–2615.
4. Peiris JS, Poon LL, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol 2009; 45:169–173.
7. Center for Disease Control and Prevention (CDC). Updated interim recommendations: HIV-infected adults and adolescents – considerations for clinicians regarding 2009 H1N1 influenza
. [Accessed October 2009]
8. Klein NC, Chak A, Chengot M, Johnson DH, Cunha BA. Fatal case of pneumonia associated with pandemic (H1N1) 2009 in HIV-positive patient. Emerg Infect Dis 2010; 16:149–150.
9. Radwan HM, Cheeseman SH, Lai KK, Ellison RT III. Influenza in human immunodeficiency virus-infected patients during the 1997–1998 influenza season. Clin Infect Dis 2000; 31:604–606.
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