*Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, †Harvard Medical School, Boston, MA, ‡Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA
F. M. Marty received research grant support and consulting honoraria from the GlaxoSmithKline (zanamivir) and is a consultant for the Influenza Combination Antiviral Focus Groups, Social and Scientific Systems, Inc.
To the Editors:
In April 2009, the first cases of swine-origin influenza A (H1N1) in the United States were characterized by the Centers for Disease Control and Prevention, with a global pandemic following shortly after.1 Cases ranged from asymptomatic to severe, with young age, pregnancy, and immunosuppression portending risk for more severe disease.2,3 Data are emerging on H1N1 infection in HIV-1-infected adults, with evidence suggesting that those on antiretroviral therapy (ART) fared similarly to the general population.4,5 Here, we report on 21 cases of influenza A infection in HIV-positive adults diagnosed at 2 Boston academic hospitals during the 2009 influenza season.
The study was reviewed and approved by the Partners Institutional Review Boards. We searched electronic medical records from the Massachusetts General Hospital and the Brigham and Women's Hospital for all HIV-1-infected individuals older than 18 years who had a rapid influenza test, direct fluorescent antibody influenza test, or an influenza A polymerase chain reaction test performed between April 2009 and June 2010 inclusive. Patients with any positive influenza A test were included. We assessed baseline CD4 counts and viral loads, defined as the most recent value within 4 months of influenza A infection. In addition, we documented the current use of ART, 2009 H1N1 Influenza A vaccination status, medical comorbidities, influenza treatment, and clinical outcomes, such as hospitalization, intensive care monitoring, and death. We tested for differences in characteristics of patients who were hospitalized from patients who were not hospitalized, using Fisher exact test for categorical variables and t tests or Wilcoxon rank sum for continuous variables, as guided by normality of the data.
Two hundred thirteen charts were identified and reviewed in detail. Of these charts, 21 adults were HIV-1 infected and had at least 1 positive diagnostic test for influenza A in the specified period. The age of this cohort ranged between 32 and 67 years (median, 46 years), with 38% women. Overall, 33% patients were whites, 43% Hispanic, and 24% blacks. None of these patients were vaccinated for H1N1 before their influenza infection. All but 2 patients were receiving ART within 4 months of influenza A infection. The median CD4 count was 458 cells per milliliter (range, 56-1046 cells/mL). Fifteen patients had undetectable viral loads, whereas the remaining 6 patients had viral loads greater than 2000 copies per milliliter (range, 2290 to >1 million copies/mL). Nineteen patients were treated with oseltamivir, and 1 of these 19 patients was also treated with rimantadine for 3 days. Two patients were treated with twice the recommended dose of oseltamivir at 150 mg twice daily. Seven patients required hospitalization; 1 required intensive care and died after 16 days of hospitalization. Table 1 compares hospitalized versus nonhospitalized patients. Hospitalized patients had a median length of stay of 3 days (range, 1-28 days). Patients who were hospitalized had a lower CD4 count (median, 240 versus 585 cells/mL; P = 0.009) and were less likely to have nondetectable viral loads (29% versus 93%; P = 0.006). Twelve patients had medical comorbidities, including 6 of the 7 hospitalized patients (P = 0.16). These included obesity (body mass index > 30), chronic obstructive pulmonary disease, asthma, active smoker, and diffuse large B-cell lymphoma (1 patient on chemotherapy and 1 patient in remission).
HIV-positive adults coinfected with the 2009 influenza A virus from our Boston cohort were similar to 3 other case series-with more than 80% taking ART, average CD4 counts in the 400-500 cells per milliliter range, and undetectable viral loads in more than 70% of the cohort.4-6 Few cases of severe H1N1 infection in HIV-positive individuals have been reported.7,8 In a Spanish cohort of 26 hospitalized HIV-positive patients with H1N1, 3 required intensive care, and no deaths were reported.4 In contrast, Chilean investigators reported only 3 hospitalizations among 30 patients coinfected with HIV and H1N1 and no fatalities.5 Hospitalized patients in that cohort had a mean CD4 of 506 cells per milliliter (higher than the mean among nonhospitalized patients), and all had nondetectable viral loads. The proportion of patients hospitalized in our cohort was higher than that reported in Chile, despite similar baseline characteristics; furthermore, patients in our study who required hospitalization tended to have lower CD4 counts and higher viral loads compared with those who did not require hospitalization. Finally, a case series from Singapore demonstrated 11 HIV-positive individuals with confirmed H1N1, 6 of whom required hospitalization without any requirements for intensive care and no fatalities.6 These series did not comment on CD4 count or viral load in hospitalized and nonhospitalized individuals.
When all the case series are combined, there is a case fatality rate of 1 in 88 (1.14%, 95% confidence interval, 0.03% to 6.17%). These published case series likely underestimate the total burden of H1N1 infection in HIV-positive individuals, as those with mild H1N1 infection are likely less inclined to seek care and will not have confirmation of infection. Data from these series suggest that individuals with well-controlled HIV had similar clinical outcomes as individuals without HIV after infection with 2009 H1N1 influenza. However, in our series, there was a trend toward more severe disease in individuals with detectable viral loads and lower CD4 counts. The numbers of HIV-positive individuals who were coinfected with H1N1 infection are still emerging, and we are likely to have more information regarding virologic parameters and severity of infection in the near future. Our case series suggests that HIV-positive patients with lower CD4 counts or detectable viral loads had more severe 2009 influenza A infection.
Isaac I. Bogoch, MD*†
Jason R. Andrews, MD*†
Francisco M. Marty, MD‡†
Elizabeth L. Hohmann, MD*†
*Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA †Harvard Medical School, Boston, MA ‡Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA
1. Dawood FS, Jain S, Finelli L, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med
2. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med
3. Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med
4. Riera M, Payeras A, Marcos MA, et al. Clinical presentation and prognosis of the 2009 H1N1 influenza A infection in HIV-1-infected patients: a Spanish multicenter study. AIDS
5. Perez CM, Dominguez MI, Ceballos ME, et al. Pandemic influenza A (H1N1) in HIV-1-infected patients. AIDS
. 2010 [epub ahead of print].
6. Isais F, Lye D, Llorin R, et al. Pandemic (H1N1) 2009 influenza in HIV-infected adults: clinical features, severity, and outcome. J Infect
7. Mora M, Rodriguez-Castellano E, Pano-Pardo JR, et al. Influenza A pandemic (H1N1) 2009 virus and HIV. Emerg Infect Dis
8. Barchi E, Prati F, Parmeggiani M, et al. Pandemic (H1N1) 2009 and HIV co-infection. Emerg Infect Dis