Abstract Purpose The recent Ebola epidemic that devastated West Africa has infected and killed more health care providers than any other outbreak in the history of this virus. An improved ...understanding of pathogen transmission and the institution of strategies to protect health care providers against infection are needed in infectious disease outbreaks. This review connects what is known about Ebola virus transmission with personal protective equipment (PPE) designed to arrest nosocomial transmission. Methods Articles pertaining to filovirus transmission and PPE in filovirus outbreaks were reviewed and findings are presented. In addition, studies that evaluated PPE and donning and doffing strategies are presented. Findings PPE is one step in a comprehensive infection prevention and control strategy that is required to protect health care providers. Given that the Ebola virus is primarily transmitted through direct contact of mucous membranes and cuts in the skin with infected patients and/or their bodily fluids, it is necessary to cover these potential portals of infection with PPE as part of a structured and instructed donning and doffing procedure. Implications Current recommendations about PPE and the donning and doffing processes are based on anecdotal experience. However, the use of non-human viruses can help provide evidence-based guidelines on both PPE and donning and doffing processes.
Summary Background Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel ...tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. Methods In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov , number NCT01815736. Findings Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4·1%, 95% CI 1·6–6·7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients 21% vs 76 16%). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group. Interpretation Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes. Funding Gilead Sciences.
Purpose Incarceration may contribute to HIV transmission by disrupting stable partnerships and promoting high-risk partnerships. We investigated incarceration and high-risk partnerships among African ...Americans in North Carolina. Methods We conducted a weighted analysis using the North Carolina Rural Health Project ( N = 320), a population-based case-control study of HIV among African Americans. We measured associations between timing and duration of incarceration and high-risk partnerships (multiple partnerships or sex trade for money or drugs). Results Duration of incarceration appeared to be more important than how long ago incarceration occurred. After adjustment for sociodemographic indicators, high-risk partnerships were associated with short-term (<1 month) incarceration of the respondent versus no respondent incarceration (men: adjusted prevalence ratio (aPR) 1.9, 95% confidence interval (95% CI) 1.2–2.8; women: aPR 3.1, 95% CI 1.2–8.3). High-risk partnerships also were associated with incarceration of a partner versus no partner incarceration (men: aPR 1.8, 95% CI 1.1–3.0; women: aPR 2.0, 95% CI 1.1–3.8). Among men, associations remained when adjusting for substance use. Among women, adjustment for substance use weakened estimates due to the strong correlation between substance use and incarceration. Conclusions HIV-prevention programs targeting currently and formerly incarcerated individuals and their partners may decrease HIV in African American communities with high incarceration rates.
Purpose We compared mortality rates among state prisoners and other state residents to identify prisoners’ health care needs. Methods We linked North Carolina prison records with state death records ...for 1995–2005 to estimate all-cause and cause-specific death rates among black and white male prisoners ages 20−79 years and used standardized mortality ratios (SMRs) to compare these observed deaths with the expected number on the basis of death rates among state residents. Results The all-cause SMR of black prisoners was 0.52 (95% confidence interval, 0.48−0.57), with fewer deaths than expected from accidents, homicides, cardiovascular disease, and cancer. The all-cause SMR of white prisoners was 1.12 (95% confidence interval, 1.01−1.25) with fewer deaths than expected for accidents but more deaths than expected from viral hepatitis, liver disease, cancer, chronic lower respiratory disease, and HIV. Conclusions The mortality of black prisoners was lower than that of black state residents for both traumatic and chronic causes of death. The mortality of white prisoners was lower than that of white state residents for accidents but greater for several chronic causes of death. Future studies should investigate the effect of prisoners’ preincarceration and in-prison morbidity, the prison environment, and prison health care on prisoners’ patterns of mortality.
Abstract Background Women who have been in prison carry a greater lifetime risk of HIV for reasons that are not well understood. This effect is amplified in the Southeastern United States, where HIV ...incidence and prevalence is especially high among African-American (AA) women. The role of consensual sexual partnerships in the context of HIV risk, especially same-sex partnerships, merits further exploration. Methods We conducted digitally recorded qualitative interviews with 29 AA women (15 HIV positive, 14 HIV negative) within 3 months after entry into the state prison system. We explored potential pre-incarceration HIV risk factors, including personal sexual practices. Two researchers thematically coded interview transcripts and a consensus committee reviewed coding. Results Women reported complex sexual risk profiles during the 6 months before incarceration, including sex with women as well as prior sexual partnerships with both men and women. Condom use with primary male partners was low and a history of transactional sex work was prevalent. These behaviors were linked with substance use, particularly among HIV-positive women. Conclusions Although women may not formally identify as bisexual or lesbian, sex with women was an important component of this cohort's sexuality. Addressing condom use, heterogeneity of sexual practices, and partner concurrency among at-risk women should be considered for reducing HIV acquisition and preventing forward transmission in women with a history of incarceration.
Summary Background Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% ...reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. Methods In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov , numbers NCT01780506 and NCT01797445. Findings We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI −0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change −3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change −1·30 vs –2·86; p<0·0001) and hip (−0·66 vs –2·95; p<0·0001) at 48 weeks. Interpretation Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Funding Gilead Sciences.
Summary Background The integrase inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in a ...single tablet given once daily. We compared the efficacy and safety of EVG/COBI/FTC/TDF with standard of care—co-formulated efavirenz (EFV)/FTC/TDF—as initial treatment for HIV infection. Methods In this phase 3 trial, treatment-naive patients from outpatient clinics in North America were randomly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF, once daily, plus matching placebo. Patients and study staff involved in giving study treatment, assessing outcomes, and collecting and analysing data were masked to treatment allocation. Eligibility criteria included screening HIV RNA concentration of 5000 copies per mL or more, and susceptibility to efavirenz, emtricitabine, and tenofovir. The primary endpoint was HIV RNA concentration of fewer than 50 copies per mL at week 48. The study is registered with ClinicalTrials.gov , number NCT01095796. Findings 700 patients were randomly assigned and treated (348 with EVG/COBI/FTC/TDF, 352 with EFV/FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF; 305/348 (87·6%) versus 296/352 (84·1%) of patients had HIV RNA concentrations of fewer than 50 copies per mL at week 48 (difference 3·6%, 95% CI −1·6% to 8·8%). Proportions of patients discontinuing drugs for adverse events did not differ substantially (13/348 in the EVG/COBI/FTC/TDF group vs 18/352 in the EFV/FTC/TDF group). Nausea was more common with EVG/COBI/FTC/TDF than with EFV/FTC/TDF (72/348 vs 48/352) and dizziness (23/348 vs 86/352), abnormal dreams (53/348 vs 95/352), insomnia (30/348 vs 49/352), and rash (22/348 vs 43/352) were less common. Serum creatinine concentration increased more by week 48 in the EVG/COBI/FTC/TDF group than in the EFV/FTC/TDF group (median 13 μmol/L, IQR 5 to 20 vs 1 μmol/L, −6 to 8; p<0·001). Interpretation If regulatory approval is given, EVG/COBI/FTC/TDF would be the only single-tablet, once-daily, integrase-inhibitor-based regimen for initial treatment of HIV infection. Funding Gilead Sciences.
Objectives To characterize the rate of decline of forced expiratory volume in 1 second (FEV1 ) in children and adolescents with cystic fibrosis and to identify and compare risk factors associated ...with FEV1 decline. Study design The rate of decline in FEV1 % predicted over 3 to 6 years in 3 different age groups was determined. Risk factors for decline were identified and compared among and within age groups as a function of disease severity with repeated-measures, mixed-model regression. Results Mean (±SD) baseline FEV1 % predicted was 88.4% ± 20.5% for 6- to 8-year-olds (n = 1811), 85.3% ± 20.8% for 9- to 12-year-olds (n = 1696), and 78.4% ± 22.0% for 13- to 17-year-olds (n = 1359). Decline in FEV1 % predicted/year was −1.12, −2.39, and −2.34, respectively. High baseline FEV1 and persistent crackles were significant independent risk factors for decline across all age groups. Female sex, Pseudomonas aeruginosa infection, low weight-for-age, sputum, wheezing, sinusitis, pulmonary exacerbations treated with intravenous antibiotics, elevated liver test results, and pancreatic insufficiency were also identified as independent risk factors in some age groups. Conclusions This study identifies risk factors for FEV1 decline in children and adolescents with cystic fibrosis. Clinicians should not be reassured by high lung function, particularly in young children, because this factor, among others, is independently associated with steeper decline in FEV1.
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