17th CROI. San Francisco. PB 801. Abbreviations: NPS, Nasopharyngeal swab; HAART, Highly Active Antiretroviral Therapy; TDF, tenofovir; FTC, emtricitabine; MVC, maraviroc; EFV, efavirenz; ABC, abacavir; 3TC, lamivudine; NVP, nevirapine; AZT, zidovudine; LPV/r, lopinavir/ritonavir; PCP, Pneumocystis jiroveci pneumonitis; CMV, citomegalovirus; HBP, high blood pressure; C. immitis, Coccidioides immitis; d, days; ILI, influenza-like illness. § All patients were treated with Oseltamivir 75 mg PO or nasogastric tube, bid, at least five days. ¥ days elapsed from symtoms onset or clinical worsening to medical evaluation, days. ǂ CD4+ cells per µL/Viral Load: RNA copies per mL. λ Confirmed H1N1 2009 case: rRT-PCR positive for H1N1 2009; Probable H1N1 2009 case: rRT-PCR positive for Influenza A but seasonal H3, H1 negative. ^ Patient with acute respiratory illness and recent close contact with a person with influenza like illness. * Syndrome of viral pneumonia probably related to influenza A H1N1 2009. ** Pneumonia more probably related to disseminated coccidioidomycosis than Influenza A H1N1 2009. *** Hospital acquired 2009 H1N1 Influenza A. Patient with previous diagnosis of CMV/P. jiroveci pneumonitis and a favorable clinical evolution (negative for H1N1 2009). Later, his clinical/respiratory condition worsened and 2 days later tested positive for H1N1 2009. He died on day 33 of illness. Case Sex/Age Evaluation date (days)¥ CD4+/HIV- Viral load ǂ and HAART regimen 08-09 seasonal influenza immuniza- tion Co- morbiditi- es other than HIV infection Influenza -Like- Illness Pneumonia Hospitali- zation/me -chanical ventilation H1N1 2009 Case definition λ/ Co- infectant agent (CDC) HIV stage Outcome 1 Male, 44 April 23 (8 d) 336/<50 TDF/FTC- MVC No Smoking Yes No No Probable A2 Survived 2 Female, 53 April 24 (2 d) 88/<50 TDF/FTC- EFV No Obesity Yes Yes * Interstitial Yes/no Confirmed AIDS C3 Survived 3 Male, 51 April 25 (2 d) 627/<50 ABC/3TC- NVP No No Yes No No Confirmed A1 Survived 4 Male, 20 April 29 (1 d) 431/177 TDF/FTC- EFV No Smoking Yes No No Confirmed / Rhinovirus A2 Survived 5 Male, 35 April 29 (1 d) 351/<50 AZT/3TC- EFV No Smoking No^ No No Probable A2 Survived 6 Male, 50 April 29 (2 d) 579/<50 TDF/ABC- LPV/r Yes Smoking, dyslipidem ia Yes No No Confirmed A1 Survived 7 Male, 35 May 1 (2 d) 569/8,930 No (HIV+ status previously known) No No Yes No No Probable A1 Survived 8 Male, 47 May 5 (6 d) 945/<50 TDF/FTC- EFV No Smoking Yes Yes ** Interstitial Yes/no Probable/ lung and lymph node C. immitis AIDS C1 Survived 9 Male, 50 May 12 (2 d) 399/<50 AZT/3TC- LPV/r Yes No Yes No No Confirmed A2 Survived 10 Male, 49 May 13 (2 d) 3/100,000 No (Newly diagnosed HIV infection) No Smoking, HBP Yes Yes *** Interstitial Yes/Yes Probable/ PCP and CMV pneumo- nitis AIDS C3 Died (respiratory failure) 11 Male, 42 June 26 (2 d) 434/<50 AZT/3TC- LPV-r No Smoking Yes No No Confirmed A2 Survived Introduction Period of phone survey Have you had the flu? H1N1 2009 cases (n=11, 1%) Patients with nasopharyngeal swab (n=20, 1.9%) Patients seen at the ER for respiratory symptoms (n=27, 2.6%) Cohort of active HIV-infected patients at INCMNZ (n=1017) Hospitalized cases (n=3, 27%) Ambulatory cases (n=8, 73%) Deaths (n=1, 9%) Table 1. Study design. Table 4.Clinical and laboratory characteristics at presentation of 2009 H1N1 cases among HIV-infected and HIV non-infected patients. (*) Before medical evaluation. Table 3. Demographics, comorbidities, seasonal influenza immunization, severity and outcome characteristics among HIV-infected and HIV non-infected patients. Table 4. Clinical and laboratory characteristics at presentation of H1N12009 cases among HIV-infected and HIV non-infected patients. Characteristic H1N1 2009 Influenza A cases at INCMNSZ HIV-infected (n=11) HIV non-infected (n=94) p Median duration of symptoms,* days (min-max) 2 (1-8) 2 (0-13) 0.29 History of fever, n(%) 10 (90) 53 (82) 0.45 Documented fever, n(%) 4 (36) 67 (71) 0.004 Diarrhea, n(%) 4 (36) 10 (16) 0.22 Rhinorrhea, n(%) 7 (63) 53 (56) 0.89 Cough, n(%) 10 (90) 63 (63) 0.2 Conjunctivitis, n(%) 4 (36) 14 (21) 0.49 Odynophagia, n(%) 5 (45) 59 (63) 0.43 Dyspnea, n(%) 1 (9) 28 (30) 0.27 Myalgia, n(%) 5 (45) 41 (64) 0.4 Headache, n(%) 4 (36) 61 (65) 0.13 Arthralgia n(%) 2 (18) 41 (64) 0.012 Nausea, n(%) 1 (9) 6 (6) 0.59 Vomiting, n(%) 1 (9) 4 (6) 0.76 Malaise, n(%) 6 (54) 43 (67) 0.63 Heart rate >90, n(%) 6 (54) 37 (63) 0.81 Respiratory rate >20, n(%) 4 (36) 29 (49) 0.6 Blood pressure <90/60, n(%) 1 (9) 0 0.2 SaO2 <90%, n(%) 1 (9) 8 (14) 0.9 WBC > 10 000, n(%) 4 (36) 8 (27) 0.8 (*) Before medical evaluation. Characteristic H1N1 2009 Influenza A cases at INCMNSZ HIV-infected (n=11) HIV non-infected(n=94) P Male (%) 10 (91) 38 (40) 0.004 Median age (min-max) 47(20-53) 36 (16-82) 0.12 Obesity, BMI >30 n(%) 1 (9) 17 (18) 0.74 Current smoker, n(%) 7 (63) 12 (13) 0.001 High blood pressure n(%) 1 (91) 13 (14) 0.97 Comorbid condition other than HIV, n(%) 3 (27) 49 (52) 0.21 Seasonal 08-09 influenza immunization, n(%) 2 (18) 32 (34) 0.38 Mild infuenza cases, n(%) 8 (73) 70 (74) 0.81 Hospitalized, n(%) 3 (27) 24 (25) 0.81 Severe cases, n(%) 1 (9) 7 (7) 0.68 Death, n(%) 1 (9) 5 (5) 0.86 Conclusions Methods (*)Mild: No pneumonia and ambulatory care. Moderate: Pneumonia or hospitalization. Severe: Requiring Invasive ventilation or admission to ICU. ( + ) ≥ 1 visit in the last 6 mo. Characteristics HIV cohort n=1017 P Patients interviewed by phone n=201 P H1N1 2009/HIV cases n=11 Male n(%) 896 (88) 0.9 177 (88) 1 10 (91) Median age (range) 39 (18-79) 0.7 40 (18-79) 0.1 47 (20-59) HIV viral load <400 copies /mL n(%) 810 (80) 0.8 162 (81) 1 9 (82) Median CD4+T cells/µL (range) 408 (3-1957) 0.1 416 (3-1957) 0.6 432 (3-945) CD4+ <200 cells/µL, n(%) 163 (16) 0.9 32 (16) 0.6 2 (18) On April 23, 2009, Canadian and US laboratories confirmed the presence of a new strain of influenza A virus (H1N1 2009) in respiratory specimens from HIV non-infected individuals with severe pneumonia in Mexico. During the influenza outbreak measures were taken to identify possible H1N1 2009 cases among patients from the HIV cohort of the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), including a telephone survey to evaluate the proportion of patients who developed respiratory symptoms (acute respiratory illness [ARI] and influenza –like illness [ILI]. In this report we describe all cases of H1N1 2009 in HIV-infected patients (H1N1 2009/HIV) evaluated at INCMNSZ during the first months of the outbreak (April to June, 2009) and their clinical characteristics, severity and outcome were compared with H1N1 2009 cases among HIV non-infected subjects. Patients All patients with confirmed HIV infection and any ARI/ILI who were seen at INCMNSZ from April to June, 2009. H1N1 2009 cases among HIV non-infected patients diagnosed in the same time period and with available information were used as controls. CRF included: demographics, co-morbidities, seasonal 08-09 influenza immunization status, duration of symptoms, physical exam, and pulse oximetry. Laboratory and imaging were performed at the discretion of attending physicians. Data on recent CD4+T cell count and HIV-RNA viral load, HAART regimen, and HIV-related events were obtained from the HIV Clinic database. Microbiologic studies Nasopharyngeal swabs (NPS) were tested for H1N1 2009 by rRT-PCR following the CDC protocol. All NPS, were also tested by multiplex RT-PCR for other respiratory viruses (x-TAG™ Luminex Diagnostics): influenza A subtypes H5 avian and H3-H1 seasonal, influenza B, respiratory syncytial virus subtypes A and B, human metapneumovirus, rhinovirus/enterovirus, parainfluenza 1-4, coronavirus (SARS, NL63, HKU1, 229E), and adenovirus. In suspected pneumonia cases: blood culture and sputum or bronchoalveolar lavage were collected. Respiratory samples were cultured and Gram, Grocott and acid-fast stained. Urine was processed for Streptococcus pneumoniae and Legionella pneumophila antigens. In a telephone survey during the H1N1 2009 outbreak in Mexico City, 20% of a sample of HIV-infected patients reported having an ARI/ILI. Only 22.5% seeked medical care during that period, all but one at INCMNSZ. HIV-infected patients represented a small fraction of all H1N1 2009 cases seen at INCMNSZ; however, HIV- infected patients with ARI were more likely to test positive for H1N1 2009 than non-HIV infected subjects, (OR 7; 95% CI 2.8-17.3; P<0.001). H1N1 2009 was the main cause of respiratory symptoms in HIV-infected patients who seeked care during the study period (55%) and H1N1 2009 was the only Influenza virus identified. Hospitalization rate, use of invasive mechanical ventilation and survival were similar between HIV-infected and HIV non-infected subjects who had H1N1 2009 influenza. Among HIV-infected subjects with H1N1 2009, only 3 were hospitalized (1 died), all of whom had AIDS. In contrast, mild Influenza occurred in patients with CD4 >300 cells/µL. Late stage of HIV disease and poor HIV control may influence the severity and outcome of H1N1 2009 in HIV-infected individuals. Table 2. Characteristics by subgroups of the INCMNSZ HIV Cohort. 6/11 (54%) 2009H1N1/HIV were diagnosed in the first week after the epidemic alert. Figure 1. Identification and clinical description of H1N1 2009/HIV cases § In hospital (prolective) Telephone survey (retrolective) All patients with respiratory symptoms were evaluated at theEmergency Room (ER) and a Case Report Form (CRF) was completed. Subjects were randomly selected from the INCMNSZ HIV cohort (active patients + ). ILI/ARI cases identified at the respiratory triage: - Clinical evaluation. - Nasopharyngeal swab. - Standardized questionnaire. - Oseltamivir 75mg PO bid, 5 days. A standardized questionnaire was applied by an ID physician looking for: - Respiratory symptoms during the epidemic alert. - Seasonal influenza vaccination status. - Patients who seeked for medical care. Ambulatory cases: - Telephone contact for follow-up Hospitalized cases: - Severity of illness* - Outcome. Analysis - Data were compared between HIV-infected and HIV non-infected subjects with H1N1 2009 Analysis - Descriptive statistics. Study period: April – June 2009. Figure 3. Telephone survey. 77 (39 %) had been immunized with seasonal 08-09 influenza vaccine before the outbreak. Most common reason for not being immunized was related to the failure of the health care worker to prescribe the vaccine. Figure 2. The outbreak. From April 22th to June 30th 2009, 832 NPS were collected at the ER. Twenty respiratory samples (2.4%) were taken from HIV-infected patients. 131 (16%) respiratory samples were H1N1 2009 positive. 11 cases were from HIV-infected patients, representing 8.3% of all samples tested positive. Positivity rate for H1N1 2009 in HIV-infected patients was 55% (11/20) and was higher than HIV non-infected patients, 15% (120/812 [OR 7 95%CI 2.8-17.3, P<0.001]. 20% 80% 15% 5% 80% 89% 11% New Swine-Origin Influenza A (H1N1)v in HIV-Infected Patients During the 2009 Outbreak in Mexico City Campos-Loza Ariel*, Soto-Ramírez Luis, Sierra-Madero Juan, Crabtree-Ramírez Brenda, Galindo-Fraga Arturo, Moreno-Espinosa Sarbelio, Guerrero M Lourdes, Ruiz-Palacios Guillermo M. HIV-Clinic. Infectious Diseases Department. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán P-154 Results Number of cases Date Contact information: Ariel Campos, MD. arielrash@hotmail.com View publication stats View publication stats