Publications by authors named "Nila J Dharan"

19 Publications

  • Page 1 of 1

Long-term protection from HIV infection with oral HIV pre-exposure prophylaxis in gay and bisexual men: findings from the expanded and extended EPIC-NSW prospective implementation study.

Lancet HIV 2021 08 1;8(8):e486-e494. Epub 2021 Jul 1.

Clinic 16, St Leonards, NSW, Australia.

Background: Daily pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but few long-term data are available on effectiveness and adherence in real-world settings. Here, we report trends in HIV incidence over 3 years in individuals at high risk who were prescribed PrEP in New South Wales (NSW), as well as adherence before the transition to subsidised PrEP.

Methods: Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) was a pragmatic, prospective, single-arm, implementation study of daily, oral PrEP in 31 sites (sexual health clinics, general practices, and a hospital) in NSW, Australia. Eligible participants were HIV-negative adults (aged ≥18 years) who were at high risk of HIV infection as defined in local PrEP guidelines. Participants were prescribed coformulated (once-daily, oral tablet) tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP and were followed up with HIV testing, sexually transmitted infection testing, and PrEP dispensing. Originally planned for 3700 participants followed for 1 year, the study was expanded so that all eligible participants in the state could obtain PrEP and extended until publicly subsidised PrEP became available in Australia. The primary outcome was new HIV infection among all participants who were dispensed PrEP at least once and had at least one follow-up HIV test result. Adherence was estimated by medication possession ratio (MPR), defined as the proportion of PrEP pills dispensed in 90 days, assuming daily dosing. This study is registered with ClinicalTrials.gov, NCT02870790.

Findings: Between March 1, 2016, and April 30, 2018, we enrolled 9709 participants. 9596 participants were dispensed PrEP, of whom 9448 (98·3%) were gay or bisexual men. Participants were followed up until March 31, 2019, with at least one follow-up HIV test available in 9520 (99·2%) participants. Mean MPR declined from 0·93 to 0·64 from the first to the ninth quarter. There were 30 HIV seroconversions over 18 628 person-years, an incidence of 1·61 per 1000 person-years (95% CI 1·13-2·30). Being younger, living in a postcode with fewer gay men, reporting more risk behaviours at baseline, and having an MPR of less than 0·6 were each univariately associated with increased HIV incidence. In the final year of follow-up, when PrEP was mostly purchased rather than provided free by the study, HIV incidence remained low at 2·24 per 1000 person-years (1·46-3·44).

Interpretation: HIV incidence remained low over up to 3 years of follow-up, including during a transition from study-provided to publicly subsidised PrEP. In a setting of affordable PrEP and associated health-care services, very low HIV incidence of 1 to 2 per 1000 person-years can be maintained in gay and bisexual men who were previously at high risk.

Funding: New South Wales Ministry of Health, Australian Capital Territory Health Directorate, Gilead Sciences.
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http://dx.doi.org/10.1016/S2352-3018(21)00074-6DOI Listing
August 2021

HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.

Nat Med 2021 06 7;27(6):1006-1011. Epub 2021 Jun 7.

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.
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http://dx.doi.org/10.1038/s41591-021-01357-yDOI Listing
June 2021

Comorbidity Medications Are Dispensed to More People Receiving Antiretroviral Therapy for HIV Compared with the General Population in Australia.

AIDS Res Hum Retroviruses 2020 04 16;36(4):291-296. Epub 2020 Jan 16.

Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

Medical comorbidities occur in more persons with HIV than without HIV. We used a nationally representative 10% sample of 2016 Pharmaceutical Benefits Scheme (PBS) dispensing data to compare the proportions of antiretroviral therapy (ART)-purchasing and non-ART-purchasing patients who also purchased prescriptions for medical comorbidities. Each patient who purchased ART was compared with two gender- and age group-matched patients who did not purchase ART in the same year. We calculated the proportions of patients who also purchased coprescriptions used for hypertension, dyslipidemia, diabetes, cancer, low bone mineral density, and mental health, defined using PBS medication coding categories, and the resulting odds ratios. A total of 1,973 ART-purchasing patients in our sample were matched to 3,946 non-ART-purchasing patients. Compared with non-ART-purchasing patients, a greater proportion of ART-purchasing patients also purchased medications for dyslipidemia (19.8% vs. 16.6%; -value = .003), low bone mineral density (1.5% vs. 0.8%; -value = .02), and mental health (29.1% vs. 15.3%; -value < .0001); a lower proportion purchased diabetes medications (4.8% vs. 6.5%; -value = .009). These differences remained when our analysis was restricted to persons >55 years of age. Rates of multimorbidity (dispensed ≥2 medications for chronic conditions) were also higher among ART-purchasing patients (19.0% vs. 15.9%; -value = .003). Using a nationally representative sample of prescription dispensing data, we found that higher proportions of ART-purchasing patients purchased coprescriptions for common comorbidities compared with non-ART-purchasing patients. Our finding that ART-purchasing patients purchased fewer diabetes medications is surprising, but may reflect differences in population characteristics between our two groups.
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http://dx.doi.org/10.1089/AID.2019.0117DOI Listing
April 2020

Heart Transplantation From Hepatitis C-Positive Donors in the Era of Direct Acting Antiviral Therapy: A Comprehensive Literature Review.

Transplant Direct 2019 Sep 23;5(9):e486. Epub 2019 Aug 23.

Heart and Lung Transplant Unit, St Vincent's Hospital, 390 Victoria St., Darlinghurst, NSW, Australia.

While heart transplantation is a highly effective treatment in patients with advanced heart failure, the number of people waiting for a transplant exceeds the number of available donors. With the advent of direct acting antivirals (DAA) for the eradication of Hepatitis C, the heart transplant donor pool has been expanded to include donors with untreated Hepatitis C. To help with the development of future protocols for Hepatitis C-positive heart transplants, we performed a review of the literature on DAA therapy in the context of heart transplantation.

Methods: We searched MEDLINE, EMBASE, OVIDE JOURNAL, and GOOGLE SCHOLAR for papers published between 01.01.2011 and 01.06.2019 using key words "heart transplantation" associated with "hepatitis C."

Results: After removing duplicates, we screened 78 articles and retained 16 for primary analysis and 20 for sustained virologic response 12 weeks after completion of the DAA therapy (SVR-12). The data from 62 patients were extracted from these publications. Fifty-six (90%) patients had donor-derived hepatitis C and 6 (10%) patients were chronically infected with hepatitis C before transplantation. All living transplanted patients achieved SVR-12, defined as hepatitis C virus RNA below the limit of detection 12 weeks after treatment completion. Treatment duration ranged from 4 to 24 weeks. Clinically relevant modification to the dosing of immunosuppressive mediations during DAA therapy was documented in only 1 patient (1.6%). Six (14%) patients experienced rejection during DAA therapy.

Conclusions: Despite different timings of initiation of DAA therapy across the included studies, there were no differences in sustained viral clearance. Early commencement of DAA with a potentially shorter treatment duration (<8 wk) is appealing; however, further studies are required before recommending this approach.
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http://dx.doi.org/10.1097/TXD.0000000000000928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739042PMC
September 2019

HIV treatment regimens and adherence to national guidelines in Australia: an analysis of dispensing data from the Australian pharmaceutical benefits scheme.

BMC Public Health 2019 Jan 3;19(1):13. Epub 2019 Jan 3.

Kirby Institute, UNSW Sydney, Wallace Wurth Building, Sydney, NSW, 2052, Australia.

Background: Treatment guidelines for antiretroviral therapy (ART) have evolved to emphasize newer regimens that address ageing-related comorbidities. Using national Australian dispensing data we compare ART regimens with Australian HIV treatment guidelines in the context of treated comorbidities.

Methods: The study population included all individuals in a 10% sample of national data from the Australian Pharmaceutical Benefits Scheme (PBS) who purchased a prescription of ART during 2016. We defined each patient's most recently dispensed ART regimen and characterized them to evaluate regimen complexity and adherence to national HIV treatment guidelines. We then analyzed ART regimens in the context of other co-prescriptions purchased for defined comorbidities.

Results: The 1995 patients in our sample purchased 212 different ART regimens during 2016; 1524 (76.4%) purchased one of the top ten most common regimens of which 62.3% were integrase strand transfer inhibitor-based. Among the 1786 (90%) patients that purchased the most common regimens, 83.7% purchased a regimen recommended by the guidelines for initial antiretroviral therapy and 11.4% purchased antiretrovirals that are not recommended for initial therapy; < 1% of the entire cohort purchased medications not recommended for use. While most patients purchased optimal ART regimens with low potential for significant drug interactions, regimen choices in the setting of risk factors for heart disease, renal disease and low bone mineral density appeared suboptimal.

Conclusions: Australian HIV providers are prescribing ART regimens in accordance with updated treatment guidelines, but could further optimize regimens in the setting of important medical comorbidities.
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http://dx.doi.org/10.1186/s12889-018-6325-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318998PMC
January 2019

Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

Lancet HIV 2018 11 17;5(11):e629-e637. Epub 2018 Oct 17.

Liverpool Sexual Health Clinic, Liverpool, NSW, Australia.

Background: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales.

Methods: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790.

Findings: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6).

Interpretation: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level.

Funding: New South Wales Ministry of Health, Gilead Sciences.
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http://dx.doi.org/10.1016/S2352-3018(18)30215-7DOI Listing
November 2018

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial.

Hepatology 2019 03 19;69(3):1135-1150. Epub 2019 Feb 19.

Kirby Institute, UNSW Sydney, Sydney, Australia.

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm). The following outcomes were evaluated: fibrosis (APRI > 0.5 or FIB-4 > 1.45), significant fibrosis (APRI > 1.5 or FIB-4 > 3.25), hepatic flare, and resolution of elevated APRI and FIB-4 scores. Of the 4,684 enrolled into the START study, 104 did not have APRI or FIB-4 results and were excluded. Among 4,580 participants (2,273 immediate treatment; 2,307 deferred treatment), the median age was 36 years, 26.9% were female, and 30.4% were black. Three percent had an alcoholism or substance abuse history, 6.4% had hepatitis B and/or C, and 1.1% had significant fibrosis at baseline. The median CD4 count was 651, and 5.3% had HIV RNA ≤ 200. Immediate arm participants were at lower risk of developing increased fibrosis scores than deferred arm participants (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.57-0.78; P < 0.001) and more likely to have resolution of elevated baseline scores (HR 1.6; 95% CI 1.3-1.9; P < 0.001). Conclusions: Significant liver fibrosis was rare among ART-naïve HIV-positive persons with high CD4 counts. Our findings suggest a benefit of early ART in preventing the development of liver fibrosis.
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http://dx.doi.org/10.1002/hep.30296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393919PMC
March 2019

Long-term durability of HIV viral load suppression.

Lancet HIV 2017 07 4;4(7):e279-e280. Epub 2017 May 4.

Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2052, Australia. Electronic address:

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http://dx.doi.org/10.1016/S2352-3018(17)30063-2DOI Listing
July 2017

Performance of the G4 Xpert MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.

BMC Infect Dis 2016 Dec 20;16(1):764. Epub 2016 Dec 20.

Department of Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, 185 South Orange Avenue, MSB I-689, Newark, NJ, 07103, USA.

Background: The Xpert MTB/RIF (Xpert) assay is a rapid PCR-based assay for the detection of Mycobacterium tuberculosis complex DNA (MTBc) and mutations associated with rifampin resistance (RIF). An updated version introduced in 2011, the G4 Xpert, included modifications to probe B and updated analytic software.

Methods: An analytical study was performed to assess Xpert detection of mutations associated with rifampin resistance in rifampin-susceptible and -resistant isolates. A clinical study was performed in which specimens from US and non-US persons suspected of tuberculosis (TB) were tested to determine Xpert performance characteristics. All specimens underwent smear microscopy, mycobacterial culture, conventional drug-susceptibility testing and Xpert testing; DNA from isolates with discordant rifampin resistance results was sequenced.

Results: Among 191 laboratory-prepared isolates in the analytical study, Xpert sensitivity for detection of rifampin resistance associated mutations was 97.7% and specificity was 90.8%, which increased to 99.0% after DNA sequencing analysis of the discordant samples. Of the 1,096 subjects in the four clinical studies, 49% were from the US. Overall, Xpert detected MTBc in 439 of 468 culture-positive specimens for a sensitivity of 93.8% (95% confidence interval [CI]: 91.2%-95.7%) and did not detect MTBc in 620 of 628 culture-negative specimens for a specificity of 98.7% (95% CI: 97.5%-99.4%). Sensitivity was 99.7% among smear-positive cases, and 76.1% among smear-negative cases. Non-determinate MTBc detection and false-positive RIF resistance results were low (1.2 and 0.9%, respectively).

Conclusions: The updated Xpert assay retained the high sensitivity and specificity of the previous assay versions and demonstrated low rates of non-determinate and RIF resistance false positive results.
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http://dx.doi.org/10.1186/s12879-016-2039-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5168809PMC
December 2016

Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making.

Int J Infect Dis 2016 Jan 3;42:17-23. Epub 2015 Nov 3.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

The dominant approach to decision-making in public health policy for infectious diseases relies heavily on expert opinion, which often applies empirical evidence to policy questions in a manner that is neither systematic nor transparent. Although systematic reviews are frequently commissioned to inform specific components of policy (such as efficacy), the same process is rarely applied to the full decision-making process. Mathematical models provide a mechanism through which empirical evidence can be methodically and transparently integrated to address such questions. However, such models are often considered difficult to interpret. In addition, models provide estimates that need to be iteratively re-evaluated as new data or considerations arise. Using the case study of a novel diagnostic for tuberculosis, a framework for improved collaboration between public health decision-makers and mathematical modellers that could lead to more transparent and evidence-driven policy decisions for infectious diseases in the future is proposed. The framework proposes that policymakers should establish long-term collaborations with modellers to address key questions, and that modellers should strive to provide clear explanations of the uncertainty of model structure and outputs. Doing so will improve the applicability of models and clarify their limitations when used to inform real-world public health policy decisions.
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http://dx.doi.org/10.1016/j.ijid.2015.10.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996966PMC
January 2016

Improving the sensitivity of the Xpert MTB/RIF assay on sputum pellets by decreasing the amount of added sample reagent: a laboratory and clinical evaluation.

J Clin Microbiol 2015 Apr 4;53(4):1258-63. Epub 2015 Feb 4.

New Jersey Medical School-Rutgers, the State University of New Jersey, Newark, New Jersey, USA.

The Xpert MTB/RIF (Xpert) assay permits rapid near-patient detection of Mycobacterium tuberculosis in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. Xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. We evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased Xpert sensitivity compared to the recommended 3:1. The limit of detection was determined by inoculating serial dilutions of M. tuberculosis into sputum samples, preparing sputum pellets, and testing each pellet by Xpert at both sample reagent ratios. Processed sputum pellets obtained from M. tuberculosis culture-positive clinical specimens were also tested by Xpert at both ratios. Among spiked sputum pellets, the limit of detection was 1,478 CFU/ml (95% confidence interval [CI], 1,211 to 1,943) at a 3:1 ratio and decreased to 832 CFU/ml (95% CI, 671 to 1,134) at 2:1. The proportion of specimens in which M. tuberculosis was detected was greater at 2:1 than at 3:1 for almost all numbers of CFU/ml; this difference was most prominent at lower numbers of CFU/ml. Among 134 concentrated sputum pellets from the clinical study, the sensitivity of Xpert at 2:1 was greater than at 3:1 overall (80% versus 72%; P=0.03) and for smear-negative specimens (67% versus 58%; P=0.12). For Xpert testing of sputum pellets, using a lower sample reagent/pellet ratio increased M. tuberculosis detection, especially for paucibacillary specimens. Our study supports use of a 2:1 sample reagent/pellet dilution for Xpert testing of sputum pellets.
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http://dx.doi.org/10.1128/JCM.03619-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365264PMC
April 2015

Child, household, and caregiver characteristics associated with hospitalization for influenza among children 6-59 months of age: an emerging infections program study.

Pediatr Infect Dis J 2014 Jun;33(6):e141-50

From the *Influenza Division, Centers for Disease Control and Prevention; †Battelle Memorial Institute, Atlanta, GA; ‡Colorado Department of Public Health and Environment, Denver, CO; §Minnesota Department of Health, St. Paul, MN; ¶Oregon Public Health Division, Portland, OR; ‖Connecticut Emerging Infections Program, New Haven, CT; **Emory University School of Medicine and the Atlanta VA Medical Center; ††Georgia Emerging Infections Program, Atlanta, GA; ‡‡California Emerging Infections Program, Oakland, CA; §§Tennessee Department of Health; ¶¶Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN; ‖‖University of Rochester School of Medicine and Dentistry, Rochester; ***New York State Department of Health, Albany, NY; †††New Mexico Department of Health, Santa Fe; and ‡‡‡University of New Mexico, Albuquerque, NM.

Background: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites.

Methods: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization.

Results: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age <26 years [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1-2.9]; household income below the poverty threshold (OR: 2.2, 95% CI: 1.4-3.6); smoking by >50% of household members (OR: 2.9, 95% CI: 1.4-6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2-2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5-31.0), pulmonary (OR: 2.9, 95% CI: 1.9-4.4) and neurologic (OR: 3.8, 95% CI: 1.6-9.2) conditions. Full influenza immunization decreased the risk among children 6-23 months of age (OR: 0.5, 95% CI: 0.3-0.9) but not among those 24-59 months of age (OR: 1.5, 95% CI: 0.8-3.0; P value for difference = 0.01).

Conclusions: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.
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http://dx.doi.org/10.1097/INF.0000000000000283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025593PMC
June 2014

Clinical and virologic outcomes in patients with oseltamivir-resistant seasonal influenza A (H1N1) infections: results from a clinical trial.

Influenza Other Respir Viruses 2012 May 26;6(3):153-8. Epub 2011 Nov 26.

Epidemic Intelligence Service, Office of Workforce and Career Development assigned to Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Nineteen patients with oseltamivir-resistant seasonal influenza A (H1N1) infections were randomized to receive oseltamivir or placebo. Nasopharyngeal swabs were obtained, and clinical and virologic outcomes were compared, stratified by early or late treatment. Neuraminidase inhibition assay and pyrosequencing for H275Y confirmed resistance. Twelve (63%) patients received oseltamivir; 8 (67%) received late treatment. Seven (37%) patients received placebo; 6 (86%) presented >48 hours after onset. Time to 50% decrease in symptom severity, complete symptom resolution, and first negative culture were shortest among the early treatment group. While sample size prohibits a strong conclusion, future studies should evaluate for similar trends.
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http://dx.doi.org/10.1111/j.1750-2659.2011.00312.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941666PMC
May 2012

Influenza antiviral prescribing practices during the 2007-08 and 2008-09 influenza seasons in the setting of increased resistance to oseltamivir among circulating influenza viruses.

Antiviral Res 2010 Nov 23;88(2):182-6. Epub 2010 Aug 23.

Epidemic Intelligence Service, Office of Workforce and Career Development assigned to Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333, USA.

Introduction: In December 2008, new interim guidelines on the use of influenza antiviral agents were released in response to a high prevalence of circulating oseltamivir-resistant seasonal influenza A(H1N1) and adamantane-resistant influenza A(H3N2) viruses. Zanamivir, oseltamivir +/- an adamantane, or oseltamivir was recommended, depending on virus type, subtype, and local surveillance data.

Materials And Methods: Information about antiviral prescribing practices among IDSA Emerging Infections Network (EIN) members was obtained using two web-based questionnaires; one in January 2009 regarding the prior 2007-08 influenza season and one in April 2009 (prepandemic), regarding the concurrent 2008-09 season.

Results: In the 2007-08 survey, 646 (52%) of 1249 EIN members responded and in the 2008-09 season survey, 350 (27%) of 1281 responded. In 2008-09 vs. 2007-08: 59% vs. 69% prescribed or recommended antivirals for treatment (p<.0001); 48% vs. 80% prescribed oseltamivir alone and 39% vs. 10% prescribed zanamivir alone (p<.0001 for both). During 2008-09 28% reported treating fewer patients compared with 2007-08; 42% felt antivirals were less effective due to resistance and 40% felt patients had less severe illness. During 2008-09, 42% of respondents reported difficulty providing zanamivir to patients vs. 5% for oseltamivir (p<.0001). Only 11% of respondents could test for influenza A subtype. During both seasons, ~55% used local surveillance data to make treatment decisions.

Discussion: A mild winter influenza season, difficulty obtaining recommended agents, and lack of access to subtype diagnosis and surveillance data may have contributed to reduced antiviral use during 2008-09.
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http://dx.doi.org/10.1016/j.antiviral.2010.08.010DOI Listing
November 2010

Outbreak of antiviral drug-resistant influenza a in long-term care facility, Illinois, USA, 2008.

Emerg Infect Dis 2009 Dec;15(12):1973-6

Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044511PMC
http://dx.doi.org/10.3201/eid1512.081644DOI Listing
December 2009

National influenza surveillance in Vietnam, 2006-2007.

Vaccine 2009 Dec 21;28(2):398-402. Epub 2009 Oct 21.

National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam.

In 2006, national influenza surveillance was implemented in Vietnam. Epidemiologic and demographic data and a throat swab for influenza testing were collected from a subset of outpatients with influenza-like illness (ILI). During January 1, 2006 through December 31, 2007, of 184,521 ILI cases identified at surveillance sites, 11,082 were tested and 2112 (19%) were positive for influenza by reverse transcription polymerase chain reaction. Influenza viruses were detected year-round, and similar peaks in influenza activity were observed in all surveillance regions, coinciding with cooler and rainy periods. Studies are needed to ascertain the disease burden and impact of influenza in Vietnam.
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http://dx.doi.org/10.1016/j.vaccine.2009.09.139DOI Listing
December 2009

Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States.

JAMA 2009 Mar 2;301(10):1034-41. Epub 2009 Mar 2.

Epidemic Intelligence Service, Office of Workforce and Career Development Assigned to Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS A-32, Atlanta, GA 30333, USA.

Context: During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.

Objectives: To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.

Design, Setting, And Patients: Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.

Main Outcome Measures: Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.

Results: During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.

Conclusions: Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.
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http://dx.doi.org/10.1001/jama.2009.294DOI Listing
March 2009
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