Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 34 Records) |
Query Trace: Donnell Z[original query] |
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A qualitative study of barriers and opportunities for concussion communication and management among parents of youth sports athletes
Sarmiento K , Donnell Z , Bell E , Tennant B , Hoffman R . J Concussion 2019 3 BACKGROUND: Concussion, a commonly reported injury among young athletes, can lead to short- and long-term physical, cognitive, emotional, and sleep-related symptoms. Parents are in a unique position to help identify a possible concussion and to support an athlete's recovery. METHODS: This qualitative study used a focus group methodology to explore five research questions focused on two main topics: (1) parents' perception of concussion and (2) parent-athlete communication. Two authors independently reviewed notes from each of the focus groups and then generated a list of emerging themes related to five research questions. RESULTS: Parents in this study valued and were interested in discussing concussion with their athletes. However, parents were uncertain about their role in promoting concussion safety and often rely on coaches to communicate with athletes about concussion reporting and recovery. Participants described barriers their athletes may face in concussion reporting and suggested strategies to improve communication about both reporting and recovery. CONCLUSION: Concussion education efforts may benefit from promoting specific actions parents can take to prevent concussion and how to communicate effectively with their child about reporting a possible concussion. |
Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083
Mitchell KM , Boily MC , Hanscom B , Moore M , Todd J , Paz-Bailey G , Wejnert C , Liu A , Donnell DJ , Grinsztejn B , Landovitz RJ , Dimitrov DT . Lancet Reg Health Am 2023 18 100416 BACKGROUND: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia. METHODS: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy × adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated. FINDINGS: We predicted TDF/FTC at current usage (∼28%) would avert 36.3% of new HIV infections (95% credible interval 25.6-48.7%) among all Atlanta MSM over 2022-2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2-56.6%) infections vs. no PrEP and 11.9% (5.2-20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022-2026, getting ∼60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage. INTERPRETATION: If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic. FUNDING: NIH, MRC. |
Incidence of herpes simplex virus type 2 infection among African women using depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a nested randomized trial
Mugo NR , Stalter RM , Heffron R , Rees H , Scoville CW , Morrison C , Kourtis AP , Bukusi E , Beksinka M , Philip NM , Beesham I , Deese J , Edward V , Donnell D , Baeten JM . Clin Infect Dis 2021 75 (4) 586-595 BACKGROUND: Globally, women have higher herpes simplex type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM). METHODS: Within a randomized trial of the effect of three contraceptive methods - DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant - on HIV acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015-2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. FINDINGS: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI] 0.65-0.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI 0.71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI 0.89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55, 95% CI 2.78-4.48). INTERPRETATION: In a randomized trial, we found no association between HSV-2 acquisition and use of three contraceptive methods. |
Cabotegravir for HIV prevention in cisgender men and transgender women
Landovitz RJ , Donnell D , Clement ME , Hanscom B , Cottle L , Coelho L , Cabello R , Chariyalertsak S , Dunne EF , Frank I , Gallardo-Cartagena JA , Gaur AH , Gonzales P , Tran HV , Hinojosa JC , Kallas EG , Kelley CF , Losso MH , Madruga JV , Middelkoop K , Phanuphak N , Santos B , Sued O , Valencia Huamaní J , Overton ET , Swaminathan S , Del Rio C , Gulick RM , Richardson P , Sullivan P , Piwowar-Manning E , Marzinke M , Hendrix C , Li M , Wang Z , Marrazzo J , Daar E , Asmelash A , Brown TT , Anderson P , Eshleman SH , Bryan M , Blanchette C , Lucas J , Psaros C , Safren S , Sugarman J , Scott H , Eron JJ , Fields SD , Sista ND , Gomez-Feliciano K , Jennings A , Kofron RM , Holtz TH , Shin K , Rooney JF , Smith KY , Spreen W , Margolis D , Rinehart A , Adeyeye A , Cohen MS , McCauley M , Grinsztejn B . N Engl J Med 2021 385 (7) 595-608 BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.). |
Understanding the HIV epidemic among MSM in Baltimore: a modelling study estimating the impact of past HIV interventions and who acquired and contributed to infections
Silhol R , Boily MC , Dimitrov D , German D , Flynn C , Farley JE , Gelman M , Hughes JP , Donnell D , Adeyeye A , Remien RH , Beyrer C , Paz-Bailey G , Wejnert C , Mitchell KM . J Acquir Immune Defic Syndr 2020 84 (3) 253-262 INTRODUCTION: Men who have sex with men (MSM) in the United States (US) are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections. SETTING: Baltimore, US METHODS:: We used a deterministic model, parameterised and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984-2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions (PAFs). RESULTS: Condom use and ART averted 19% (95% uncertainty interval: 14-25%) and 23% (15-31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008-2017, 46% (41-52%) of incident infections were acquired by, and 35% (27-49%) of transmissions contributed by MSM aged 18-24 years old (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31-54%), 46% (25-56%), and 14% (7-28%) of transmissions, respectively. CONCLUSION: Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented since the largest percentage of HIV transmissions among Baltimore MSM are attributed to this group. |
US Centers for Disease Control and Preventions HEADS UP branding and evaluation process
Waltzman D , Hoffman R , Donnell Z , Bell E , Sarmiento K . Health Educ J 2019 79 (2) 180-194 Background: For 15 years, the US Centers for Disease Control and Prevention’s (CDC) HEADS UP education campaign has focused on increasing awareness of concussion among children to reduce adverse outcomes from this injury. Objective: To keep pace with the rapid expansion in media coverage, research, state laws and education efforts on concussion, the CDC embarked on a comprehensive evaluation effort to assess the campaign’s brand. Method: The CDC conducted a multi-step process to evaluate HEADS UP. This included surveying partner organisations and focus groups targeting key audiences. Results: The analysis demonstrated that most (70%) partner organisations have used the materials for 4 years or longer, and more than half (51%) found the materials very useful or extremely useful. Focus groups with the campaign’s target audiences yielded insights and opportunities to refresh the CDC HEADS UP brand. The need for more compelling images, prevention facts and use of eye-catching colours was signalled by all the campaign’s target audiences. Updates focused on the use of data visualisation, more emotionally compelling images and more engaging colours. The CDC also created a new tagline to focus on concussion prevention that encourages children and young people to think about protecting their brains from concussion so that they can have a safer future. Conclusion: This paper describes the process used to update the branding of an educational health promotion campaign in order to meet the needs of key audiences. Findings can help others working to keep their educational campaigns relevant and aligned with expanding and changing public health problems. |
Predicted effectiveness of daily and non-daily PrEP for MSM based on sex and pill-taking patterns from HPTN 067/ADAPT
Dimitrov D , Moore JR , Wood D , Mitchell KM , Li M , Hughes JP , Donnell DJ , Mannheimer S , Holtz TH , Grant RM , Boily MC . Clin Infect Dis 2019 71 (2) 249-255 BACKGROUND: HPTN 067/ADAPT evaluated the feasibility of daily and non-daily HIV pre-exposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York, U.S. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. METHODS: An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the iPrEx trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. RESULTS: We estimated that PrEP was highly protective (85%-96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%-88% efficacy) than in Harlem (62%-81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85% and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8-9 percentage points in Harlem and by 5-9 percentage points in Bangkok across regimens. CONCLUSIONS: Our analysis suggests that PrEP was more effective among MSM in Thailand than in the U.S. as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, non-daily PrEP was less effective than daily PrEP, especially in the U.S. where the sex act coverage associated with daily use was substantially higher. |
Brief report: Durability of the effect of financial incentives on HIV viral load suppression and continuity in care: HPTN 065 Study
El-Sadr WM , Beauchamp G , Hall HI , Torian LV , Zingman BS , Lum G , Elion RA , Buchacz K , Burns D , Zerbe A , Gamble T , Donnell DJ . J Acquir Immune Defic Syndr 2019 81 (3) 300-303 BACKGROUND: Results from the HPTN 065 study showed that financial incentives (FI) were associated with significantly higher viral load suppression and higher levels of engagement in care among patients at HIV care sites randomized to FI versus sites randomized to standard of care (SOC). We assessed HIV viral suppression and continuity in care after intervention withdrawal to determine the durability of FI on these outcomes. SETTING: A total of 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, participated in the study. METHODS: Laboratory data reported to the US National HIV Surveillance System were used to determine site-level viral suppression and continuity in care outcomes. Postintervention effects were assessed for the 3 quarters after discontinuation of FI. Generalized estimation equations were used to compare FI and SOC site-level outcomes after intervention withdrawal. RESULTS: After FI withdrawal, a trend remained for an increase in viral suppression by 2.7% (-0.3%, 5.6%, P = 0.076) at FI versus SOC sites, decreasing from the 3.8% increase noted during implementation of the intervention. The significant increase in continuity in care during the FI intervention was sustained after intervention with 7.5% (P = 0.007) higher continuity in care at FI versus SOC sites. CONCLUSIONS: After the withdrawal of FI, findings at the 9-months postintervention withdrawal from this large study showed evidence of durable effects of FI on continuity in care, with trend for continued higher viral suppression. These findings are promising for adoption of such interventions to enhance key HIV-related care outcomes. |
Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078
Mitchell KM , Hoots B , Dimitrov D , German D , Flynn C , Farley JE , Gelman M , Hughes JP , Donnell D , Adeyeye A , Remien RH , Beyrer C , Paz-Bailey G , Boily MC . J Int AIDS Soc 2019 22 (3) e25246 INTRODUCTION: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. METHODS: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets - 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. RESULTS: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. CONCLUSIONS: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM. |
From the CDC a qualitative study of middle and high school professionals experiences and views on concussion: Identifying opportunities to support the return to school process
Sarmiento K , Donnell Z , Bell E , Hoffman R . J Safety Res 2018 68 223-229 INTRODUCTION: Current research recommends that students returning to school after a concussion should receive a return to school plan that is tailored to their individual symptoms. School professionals play important roles in designing and implementing the supports outlined in return to school plans. METHODS: This qualitative study explored middle and high school professionals' experiences with concussion, particularly their knowledge and perceptions of the injury and their experience with supporting students with concussion. Six focus groups were conducted with two to four school professionals per group, including two groups of teachers, two groups of school psychologists and counselors, and two groups of school nurses. Findings were coded into four categories: (a) challenges with identifying a concussion; (b) strategies for communicating with students about concussion; (c) barriers to implementing return to learn plans; and (d) establishing a collaborative school support team. RESULTS: School professionals who participated in the focus groups were knowledgeable about concussion and the importance of helping their student recover. Participants also understood the importance of recognizing the signs and symptoms of concussion and communicating with students and parents about this injury. However, the study participants reported various challenges related to concussion identification and management, including the perceived validity of concussion symptom reporting by students. A team-based approach was mentioned across all groups as the preferred method for school-based concussion management for students. CONCLUSION: School professionals in this study were eager to address concussion in their schools, but desire guidance on how to overcome social norms around concussion identification and reporting. In addition, there is a need for consistent use of written instructions from healthcare providers to help guide return to learn (RTL) accommodations. Practical applications: The findings from this study can help inform the integration of concussion, and other health, management plans in schools. |
Seeking to improve care for young patients: Development of tools to support the implementation of the CDC Pediatric mTBI Guideline
Donnell Z , Hoffman R , Myers G , Sarmiento K . J Safety Res 2018 67 203-209 Introduction: The Centers for Disease Control and Prevention (CDC) Pediatric Mild Traumatic Brain Injury (mTBI) Guideline was created to help standardize diagnosis, prognosis, and management and treatment of pediatric mTBI. This paper describes the process CDC used to develop educational tools, and a dissemination and implementation strategy, in support of the CDC Pediatric mTBI Guideline. Methods: Two qualitative data collection projects with healthcare providers who care for pediatric patients were conducted. In-depth interviews were used in both projects. Project One examined healthcare providers’ guideline use and dissemination preferences. Project Two assessed perceptions of the CDC Pediatric mTBI Guideline educational tools. Results: Project One brought to light four key areas related to Guideline usage and dissemination preferences, specifically a need for: (1) partnership with professional medical societies; (2) integration into electronic health records, mobile apps, and websites; (3) development of continuing medical education (CME) opportunities; and (4) dissemination through healthcare system leadership. In Project Two, healthcare providers reported that the CDC Pediatric mTBI Guideline educational tools were well-organized, clear and easy to navigate, and informative. Healthcare providers also requested more information on the Guideline methodology. Discussion: Assessment of pediatric healthcare providers’ current use of clinical guidelines and preferences for educational tools yielded important insights that helped inform CDC's dissemination and implementation strategy for the Pediatric mTBI Guideline. Practical applications: The findings from these data collection projects can also inform other guideline implementation and dissemination efforts among healthcare providers. © 2018 |
Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children
Lumba-Brown A , Yeates KO , Sarmiento K , Breiding MJ , Haegerich TM , Gioia GA , Turner M , Benzel EC , Suskauer SJ , Giza CC , Joseph M , Broomand C , Weissman B , Gordon W , Wright DW , Moser RS , McAvoy K , Ewing-Cobbs L , Duhaime AC , Putukian M , Holshouser B , Paulk D , Wade SL , Herring SA , Halstead M , Keenan HT , Choe M , Christian CW , Guskiewicz K , Raksin PB , Gregory A , Mucha A , Taylor HG , Callahan JM , DeWitt J , Collins MW , Kirkwood MW , Ragheb J , Ellenbogen RG , Spinks TJ , Ganiats TG , Sabelhaus LJ , Altenhofen K , Hoffman R , Getchius T , Gronseth G , Donnell Z , O'Connor RE , Timmons SD . JAMA Pediatr 2018 172 (11) e182853 Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States. Objective: To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI. Evidence Review: The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015. Findings: The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment. Conclusions and Relevance: This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations. |
Diagnosis and management of mild traumatic brain injury in children: A systematic review
Lumba-Brown A , Yeates KO , Sarmiento K , Breiding MJ , Haegerich TM , Gioia GA , Turner M , Benzel EC , Suskauer SJ , Giza CC , Joseph M , Broomand C , Weissman B , Gordon W , Wright DW , Moser RS , McAvoy K , Ewing-Cobbs L , Duhaime AC , Putukian M , Holshouser B , Paulk D , Wade SL , Herring SA , Halstead M , Keenan HT , Choe M , Christian CW , Guskiewicz K , Raksin PB , Gregory A , Mucha A , Taylor HG , Callahan JM , DeWitt J , Collins MW , Kirkwood MW , Ragheb J , Ellenbogen RG , Spinks TJ , Ganiats TG , Sabelhaus LJ , Altenhofen K , Hoffman R , Getchius T , Gronseth G , Donnell Z , O'Connor RE , Timmons SD . JAMA Pediatr 2018 172 (11) e182847 Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study. Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI. Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search. Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking. Conclusions and Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management. |
Healthcare providers' attitudes and behaviours related to paediatric mild traumatic brain injury: results from the 2014 DocStyles survey
Sarmiento K , Donnell Z , Hoffman R , Tennant B . Brain Inj 2018 32 (7) 1-5 OBJECTIVE: Explore healthcare providers' experiences managing mTBI and better understand their use of mTBI assessment tools and guidelines. Cross-sectional Methods: A random sample of 1,760 healthcare providers responded to the web-based DocStyles survey between June 18 and 30, 2014. The sample included family/general practitioners, internists, pediatricians, and nurse practitioners who reported seeing pediatric patients. We examined their experiences with mTBI to identify opportunities to increase preparedness and improve management of mTBI. RESULTS: Fifty-nine percent of healthcare providers reported that they diagnosed or managed pediatric patients with mTBI within the last 12 months. Of those, 44.4% felt 'very prepared' to make decisions about when pediatric patients can safety return to activities, such as school and sports after a mTBI. When asked how often they use screening or assessment tools to assess pediatric patients with mTBI, almost half reported that they 'seldom' or 'never' use those resources (24.6% and 22.0%, respectively). CONCLUSION: Most healthcare providers reported seeing pediatric patients with mTBI, yet most feel only somewhat prepared to manage this injury in their practise. Broader use of screening tools and guidelines, that include clinical decision support tools, may be useful for healthcare providers who care for pediatric patients with mTBI. |
Concussion attitudes, behaviors, and education among youth ages 12-17: Results from the 2014 YouthStyles survey
Donnell Z , Hoffman R , Sarmiento K , Hays C . J Safety Res 2018 64 163-169 Introduction: This study assessed young athletes' (ages 12 to 17) concussion attitudes and behaviors, particularly their self-reported experience learning about concussion and intentions to report a concussion and disparities in these experiences. Methods: We used data from Porter Novelli's 2014 YouthStyles survey that is conducted each year to gather insights about American consumers. Results: Of the 1,005 respondents, 57% reported sports participation. Fourteen percent reported they may have had a previous concussion, and among them 41% reported having a concussion more than once while playing sports. Males (17.7%) were significantly more likely to report having a concussion than females (10.0%; χ2 (1)=7.01, p=0.008). Fifty-five percent of respondents reported having learned about what to do if they think they may have a concussion, and 92% reported that they would tell their coach if they thought they sustained a concussion while playing youth or high school sports. Youth from higher income families ($75,000-$124,999) were significantly more likely than youth from lower income families (less than $35,000) to report that they learned about what do if they suspected that they had a concussion. Conclusion: Age of athlete, parental income level, athlete's sex, and living in a metro versus non-metro area led to disparities in athletes' concussion education. There is a need for increased access to concussion education and an emphasis on customizing concussion education efforts to meet the needs of different groups. Practical application: We identified athletes' self-reported previously sustained concussions and predictors of education related to concussion. Further research is needed to explore the age, gender and income gaps in concussion education among athletes. |
In what circumstances could nondaily preexposure prophylaxis for HIV substantially reduce program costs
Mitchell KM , Dimitrov D , Hughes JP , Xia F , Donnell D , Amico KR , Bokoch K , Chitwarakorn A , Bekker LG , Holtz TH , Mannheimer S , Grant RM , Boily MC . AIDS 2018 32 (6) 809-818 OBJECTIVES: To review the main factors influencing the costs of nondaily oral preexposure prophylaxis (PrEP) with tenofovir (+/-emtricitabine). To estimate the cost reductions possible with nondaily PrEP compared with daily PrEP for different populations (MSM and heterosexual populations). DESIGN: Systematic review and data triangulation. METHODS: We estimated the required number of tablets/person/week for dosing regimens used in the HPTN 067/ADAPT (daily/time-driven/event-driven) and IPERGAY (on-demand) trials for different patterns of sexual intercourse. Using trial data, and behavioural and cost data obtained through systematic literature reviews, we estimated cost savings because of tablet reductions for nondaily versus daily oral PrEP, assuming 100% adherence. RESULTS: Among different populations being prioritized for PrEP, the median reported number of days of sexual activity varied between 0 and 2 days/week (0-1.5 days/week for MSM, 1-2 days/week for heterosexual populations). With 100% adherence and two or less sex-days/week, HPTN 067/ADAPT nondaily regimens reduced the number of tablets/week by more than 40% compared with daily PrEP. PrEP program costs were reduced the most in settings with high-drug costs, for example, by 66-69% with event-driven PrEP for French/US populations reporting on average one sex-day/week. CONCLUSION: Nondaily oral PrEP could lower costs substantially (>50%) compared with daily PrEP, particularly in high-income countries. Adherence and efficacy data are needed to determine cost-effectiveness. |
A scoping review to address the culture of concussion in youth and high school sports
Sarmiento K , Donnell Z , Hoffman R . J Sch Health 2017 87 (10) 790-804 BACKGROUND: In 2013, the National Academy of Sciences emphasized the need to develop, implement, and evaluate effective large-scale educational strategies to improve the culture of concussion in youth and high school sports. In support of this recommendation, in this article we summarize research on factors that contribute to the culture of concussion. METHODS: We conducted the literature search using 7 electronic databases. We used a scoping review method to identify studies that addressed knowledge, attitudes, behaviors, use of educational resources, and interventions related to concussion among young athletes, coaches, and parents. RESULTS: Of the 33 articles identified, most focused on concussion education (N = 15), followed by knowledge (N = 13), behaviors (N = 13), and attitudes (N = 5). Three studies addressed multiple study populations. CONCLUSIONS: The rapid spread of concussion education and awareness efforts has outpaced research on effective strategies to improve knowledge, attitudes, and behaviors that contribute to the culture of concussion. Further research is critical to inform the development and implementation of large-scale educational efforts. This research should incorporate rigorous study designs; be inclusive of diverse ages, socioeconomic status, and racial/ethnic groups; and examine opportunities to improve behavioral outcomes around concussion prevention, reporting, and management. |
The effect of oral pre-exposure prophylaxis on the progression of HIV-1 seroconversion
Donnell D , Ramos E , Celum C , Baeten J , Dragavon J , Tappero J , Lingappa JR , Ronald A , Fife K , Coombs RW . AIDS 2017 31 (14) 2007-2016 OBJECTIVE: To investigate whether oral pre-exposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. DESIGN: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. METHODS: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. RESULTS: There was a significant increase in delayed site detection of infection associated with PrEP (OR = 3.49, p = 0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (OR = 0.93, p = 0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 days versus 17 days, p = 0.05). Adjusted for Fiebig stage, viral RNA was approximately 2/3 log lower in those assigned to PrEP compared to placebo; no differences were found in Architect S/CO at any stage. CONCLUSIONS: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance. |
Financial incentives for linkage to care and viral suppression among HIV-positive patients: A randomized clinical trial (HPTN 065)
El-Sadr WM , Donnell D , Beauchamp G , Hall HI , Torian LV , Zingman B , Lum G , Kharfen M , Elion R , Leider J , Gordin FM , Elharrar V , Burns D , Zerbe A , Gamble T , Branson B . JAMA Intern Med 2017 177 (8) 1083-1092 Importance: Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits. Objective: To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. Design, Setting, and Participants: A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. Interventions: Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. Main Outcomes and Measures: Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (<400 copies/mL), assessed at each calendar quarter. Outcomes assessed through laboratory test results reported to the National HIV Surveillance System. Results: A total of 1061 coupons were dispensed for linkage to care at 18 financial incentive test sites and 39359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not previously consistently virally suppressed, the proportion virally suppressed was 4.9% higher (95% CI, 1.4%-8.5%; P = .007) at financial incentive sites. In addition, continuity in care was 8.7% higher (95% CI, 4.2%-13.2%; P < .001) at financial incentive sites. Conclusions and Relevance: Financial incentives, as used in this study (HPTN 065), significantly increased viral suppression and regular clinic attendance among HIV-positive patients in care. No effect was noted on linkage to care. Financial incentives offer promise for improving adherence to treatment and viral suppression among HIV-positive patients. Trial Registration: clinicaltrials.gov Identifier: NCT01152918. |
Design of the HPTN 065 (TLC-Plus) study: A study to evaluate the feasibility of an enhanced test, link-to-care, plus treat approach for HIV prevention in the United States
Gamble T , Branson B , Donnell D , Hall HI , King G , Cutler B , Hader S , Burns D , Leider J , Wood AF , GVolpp K , Buchacz K , El-Sadr WM . Clin Trials 2017 14 (4) 1740774517711682 Background/Aims HIV continues to be a major public health threat in the United States, and mathematical modeling has demonstrated that the universal effective use of antiretroviral therapy among all HIV-positive individuals (i.e. the "test and treat" approach) has the potential to control HIV. However, to accomplish this, all the steps that define the HIV care continuum must be achieved at high levels, including HIV testing and diagnosis, linkage to and retention in clinical care, antiretroviral medication initiation, and adherence to achieve and maintain viral suppression. The HPTN 065 (Test, Link-to-Care Plus Treat [TLC-Plus]) study was designed to determine the feasibility of the "test and treat" approach in the United States. Methods HPTN 065 was conducted in two intervention communities, Bronx, NY, and Washington, DC, along with four non-intervention communities, Chicago, IL; Houston, TX; Miami, FL; and Philadelphia, PA. The study consisted of five components: (1) exploring the feasibility of expanded HIV testing via social mobilization and the universal offer of testing in hospital settings, (2) evaluating the effectiveness of financial incentives to increase linkage to care, (3) evaluating the effectiveness of financial incentives to increase viral suppression, (4) evaluating the effectiveness of a computer-delivered intervention to decrease risk behavior in HIV-positive patients in healthcare settings, and (5) administering provider and patient surveys to assess knowledge and attitudes regarding the use of antiretroviral therapy for prevention and the use of financial incentives to improve health outcomes. The study used observational cohorts, cluster and individual randomization, and made novel use of the existing national HIV surveillance data infrastructure. All components were developed with input from a community advisory board, and pragmatic methods were used to implement and assess the outcomes for each study component. Results A total of 76 sites in Washington, DC, and the Bronx, NY, participated in the study: 37 HIV test sites, including 16 hospitals, and 39 HIV care sites. Between September 2010 and December 2014, all study components were successfully implemented at these sites and resulted in valid outcomes. Our pragmatic approach to the study design, implementation, and the assessment of study outcomes allowed the study to be conducted within established programmatic structures and processes. In addition, it was successfully layered on the ongoing standard of care and existing data infrastructure without disrupting health services. Conclusion The HPTN 065 study demonstrated the feasibility of implementing and evaluating a multi-component "test and treat" trial that included a large number of community sites and involved pragmatic approaches to study implementation and evaluation. |
Swaziland HIV Incidence Measurement Survey (SHIMS): a prospective national cohort study
Justman J , Reed JB , Bicego G , Donnell D , Li K , Bock N , Koler A , Philip NM , Mlambo CK , Parekh BS , Duong YT , Ellenberger DL , El-Sadr WM , Nkambule R . Lancet HIV 2016 4 (2) e83-e92 BACKGROUND: Swaziland has the highest national HIV prevalence worldwide. The Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national HIV incidence estimate based on prospectively observed HIV seroconversions. METHODS: A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18-49 years from 14 891 households in 575 enumeration areas in Swaziland, who underwent household-based counselling and rapid HIV testing during 2011. All individuals aged 18-49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing, answer demographic and behavioural questions in English or siSwati, and provide written informed consent were eligible for the study. We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a questionnaire at baseline and, for HIV-seronegative individuals, 6 months later. We calculated HIV incidence with Poisson regression modelling as events per person-years x 100, and we assessed covariables as predictors with Cox proportional hazards modelling. Survey weighting was applied and all models used survey sampling methods. FINDINGS: Between Dec 10, 2010, and June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting in a weighted HIV incidence of 2.4% (95% CI 2.1-2.8). Incidence was nearly twice as high in women (3.1%; 95% CI 2.6-3.7) as in men (1.7%; 1.3-2.1, p<0.0001). Among men, partner's HIV-positive status (adjusted hazard ratio [aHR] 2.67, 1.06-6.82, p=0.040) or unknown serostatus (aHR 4.64, 2.32-9.27, p<0.0001) in the past 6 months predicted HIV seroconversion. Among women, significant predictors included not being married (aHR 2.90, 1.44-5.84, p=0.0030), having a spouse who lives elsewhere (aHR 2.66, 1.29-5.45, p=0.0078), and having a partner in the past 6 months with unknown HIV status (aHR 2.87, 1.44-5.84, p=0.0030). INTERPRETATION: Swaziland has the highest national HIV incidence in the world. In high-prevalence countries, population-based incidence measures and programmes that further expand HIV testing and support disclosure of HIV status are needed. FUNDING: President's Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and Prevention. |
Effect of pregnancy on response to antiretroviral therapy in HIV-infected African women
Kourtis AP , Wiener J , King CC , Heffron R , Mugo NR , Nanda K , Pyra M , Donnell D , Celum C , Lingappa JR , Baeten JM . J Acquir Immune Defic Syndr 2016 74 (1) 38-43 BACKGROUND: While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy on response to antiretroviral therapy (ART). Hormonal, immune and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. METHODS: Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention HSV/HIV Transmission Study, Couples Observational Study, and Partners PrEP Study) from seven countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤ 45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies/ml ≥6 months after ART initiation and viral suppression was defined as viral load ≤400 copies/ml. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, WHO clinical stage III/IV and death. Linear mixed effects models were used to assess the association between pregnancy and CD4+ count and VL. All analyses were adjusted for confounders, including pre-ART CD4+ count and plasma VL. RESULTS: A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4+ count prior to ART initiation was 276 cells/mm (IQR, 209-375); median pre-ART VL was 17,511 copies/ml (IQR, 2,480-69,286). One-hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to viral suppression (adjusted HR, 1.20, 95% CI, 0.82-1.77), time to virologic failure (adjusted HR, 0.67, 95% CI, 0.37-1.22), time to WHO clinical stage III or IV (adjusted HR, 0.79, 95% CI, 0.19-3.30) or time to death (adjusted HR, 2.04, 95% CI, 0.25-16.8). Incident pregnancy was associated with an adjusted mean decrease in CD4+ T cell count of 47.3 cells/mm (p<0.001), but not with difference in VL (p=0.06). CONCLUSIONS: For HIV-infected women on ART, incident pregnancy does not affect virologic control or clinical HIV disease progression. A modest decrease in CD4+ T cell count could be due to physiologic effects of pregnancy. |
Changing clinician practices and attitudes regarding the use of antiretroviral therapy for HIV treatment and prevention: results from the HPTN 065 study
Buchacz K , Farrior J , Beauchamp G , McKinstry L , Kurth AE , Zingman BS , Gordin FM , Donnell D , Mayer KH , El-Sadr WM , Branson B . J Int Assoc Provid AIDS Care 2016 16 (1) 81-90 As part of the HPTN065 study in the Bronx, New York and Washington, the authors, we surveyed clinicians to assess for shifts in their practices and attitudes around HIV treatment and prevention. Antiretroviral therapy (ART)-prescribing clinicians at 39 HIV care sites were offered an anonymous Web-based survey at baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and 141 respondents at follow-up had similar characteristics-almost 60% were female, median age was 47 years, two-thirds were physicians, and nearly 80% were HIV specialists. The percentage who reported recommending ART irrespective of CD4 count was higher at follow-up (15% versus 68%), as was the percentage who would initiate ART earlier for patients having unprotected sex with partners of unknown HIV status (64% versus 82%), and for those in HIV-discordant partnerships (75% versus 87%). In line with changing HIV treatment guidelines during 2010 to 2013, clinicians increasingly supported early ART for treatment and prevention. |
Low risk of proximal tubular dysfunction associated with emtricitabine-tenofovir disoproxil fumarate pre-exposure prophylaxis in men and women
Mugwanya K , Baeten J , Celum C , Donnell D , Nickolas T , Mugo N , Branch A , Tappero J , Kiarie J , Ronald A , Yin M , Wyatt C . J Infect Dis 2016 214 (7) 1050-7 OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is associated with proximal tubular dysfunction (tubulopathy) when used in HIV treatment. We evaluated whether TDF causes tubulopathy when used as HIV pre-exposure prophylaxis (PrEP) and whether tubulopathy predicts clinically relevant decline (≥25%) in estimated glomerular filtration rate (eGFR). METHODS: A subgroup analysis of the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF among HIV-uninfected African men and women (Clinicaltrials.gov numberNCT00557245). Tubulopathy was assessed in concurrently obtained urine and serum at the 24-month or last on-treatment visit, pre-defined as ≥2 of: tubular proteinuria, euglycemic glycosuria, increased urinary phosphate or uric acid excretion. RESULTS: Of 1549 persons studied (776 on FTC-TDF, 773 on placebo), 64% were male and median age was 37-years. Over median 24-months of study-drug exposure, the frequency of tubulopathy was 1.7% in FTC-TDF versus 1.3% for placebo [odds ratio (OR), 95%CI: 1.30 (0.52, 3.33); p=0.68]. Tubulopathy occurred in 2 of 52 (3.8%) persons with ≥25% eGFR decline versus 3 of 208 (1.4%) without ≥25% eGFR decline [adjusted OR 95%CL: 1.39 (0.10, 14.0); p >0.99]. CONCLUSIONS: Daily oral FTC-TDF PrEP was not significantly associated with tubulopathy over 24 months nor did tubulopathy predict clinically relevant eGFR decline. |
Changing antiretroviral eligibility criteria: Impact on the number and proportion of adults requiring treatment in Swaziland
Bock NN , Emerson RC , Reed JB , Nkambule R , Donnell DJ , Bicego GT , Okello V , Philip NM , Ehrenkranz PD , Duong YT , Moore JS , Justman JE . J Acquir Immune Defic Syndr 2016 71 (3) 338-44 OBJECTIVE: Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. DESIGN: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. METHODS: Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. RESULTS: Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. CONCLUSIONS: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART. |
Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial
Mugwanya KK , Wyatt C , Celum C , Donnell D , Mugo NR , Tappero J , Kiarie J , Ronald A , Baeten JM . JAMA Intern Med 2014 175 (2) 246-54 IMPORTANCE: Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention. OBJECTIVE: To determine whether TDF-based PrEP causes eGFR decline in HIV-1-uninfected adults. DESIGN, SETTING, AND PARTICIPANTS: A per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1-uninfected members of serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012. MAIN OUTCOMES AND MEASURES: Predefined outcomes of this analysis were mean eGFR change and a 25% or greater eGFR decline from baseline. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Results: Of 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or placebo (n = 1547) groups, 63% were men. At enrollment, median age was 35 years (range, 18-64 years), and mean eGFR was 130 mL/min/1.73 m2. During a median follow-up of 18 months (interquartile range 12-27 months), mean within-group eGFR change from baseline was +0.14 mL/min/1.73 m2 for TDF, -0.22 mL/min/1.73 m2 for FTC-TDF, and +1.37 mL/min/1.73 m2 for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of -1.23 mL/min/1.73 m2 (95% CI, -2.06 to -0.40; P = .004) for TDF and -1.59 mL/min/1.73 m2 (95% CI, -2.44 to -0.74; P < .001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by 1 month after randomization, was stable through 12 months, and then appeared to wane thereafter. The respective proportions of persons who developed a confirmed 25% or greater eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different from the confirmed decline in the placebo group (0.9% and 1.3% by 12 and 24 months, respectively). CONCLUSIONS AND RELEVANCE: In this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline. |
Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial
Baeten JM , Donnell D , Mugo NR , Ndase P , Thomas KK , Campbell JD , Wangisi J , Tappero JW , Bukusi EA , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kidoguchi L , Coombs RW , Hendrix C , Marzinke MA , Frenkel L , Haberer JE , Bangsberg D , Celum C . Lancet Infect Dis 2014 14 (11) 1055-1064 BACKGROUND: Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. METHODS: We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov, number NCT00557245. FINDINGS: 4410 (99.6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0.71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0.48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio [HR] 0.67, 95% CI 0.39-1.17; p=0.16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0.15, 95% CI 0.06-0.37; p<0.0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0.07, 0.02-0.23; p<0.0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. INTERPRETATION: These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health. |
Successful discontinuation of the placebo arm and provision of an effective HIV prevention product after a positive interim efficacy result: the Partners PrEP Study experience
Ndase P , Celum C , Campbell J , Bukusi E , Kiarie J , Katabira E , Mugo N , Tumwesigye E , Wangisi J , Were E , Brantley J , Donnell D , Baeten JM . J Acquir Immune Defic Syndr 2014 66 (2) 206-12 BACKGROUND: Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations. METHODS: In July 2011, the independent Data and Safety Monitoring Board of the Partners PrEP Study, a randomized, placebo-controlled efficacy trial of daily oral antiretroviral preexposure prophylaxis (PrEP) for HIV prevention among 4747 African heterosexual HIV serodiscordant couples, recommended discontinuation of the trial's placebo arm due to demonstration of PrEP efficacy. We describe dissemination of results, discontinuation of the placebo arm, and provision of active PrEP to participants' formerly assigned placebo. RESULTS: Within 72 hours, of the Data and Safety Monitoring Board meeting the study results were publicly released and disseminated to stakeholders and study participants. Within 3 months, the study protocol was modified to permit participants initially assigned to the study's placebo arm to be offered active PrEP. Of the 1418 participants initially randomized to placebo who were clinically eligible to receive PrEP, 89.1% (1264/1418) consented. CONCLUSIONS: Prompt dissemination of a positive HIV prevention trial result and subsequent provision of effective product to research participants was feasible and efficient for >4700 HIV serodiscordant couples in East Africa. The extent to which study sponsors can assure continued product access to research participants remains a subject of discussion for future HIV prevention clinical trials. |
An intervention to support HIV pre-exposure prophylaxis (PrEP) adherence in HIV serodiscordant couples in Uganda
Psaros C , Haberer JE , Katabira E , Ronald A , Tumwesigye E , Campbell JD , Wangisi J , Mugwanya K , Kintu A , Enyakoit M , Thomas KK , Donnell D , Krows M , Kidoguchi L , Ware N , Baeten JM , Celum C , Bangsberg DR , Safren SA . J Acquir Immune Defic Syndr 2014 66 (5) 522-9 BACKGROUND: Daily pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This manuscript describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence. METHODS: The Partners PrEP Study was a placebo-controlled efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among uninfected members of HIV serodiscordant couples. An ancillary adherence study was conducted at three study sites in Uganda. Participants with <80% adherence as measured by unannounced pill count received an additional adherence counseling intervention based on Lifesteps, an evidence-based HIV treatment adherence intervention, based on principles of cognitive-behavioral theory. FINDINGS: Of the 1,147 HIV seronegative participants were enrolled in the ancillary adherence study, 168 (14.6%) triggered the adherence intervention. Of participants triggering the intervention, 62% were male; median age was 32.5 years. The median number of adherence counseling sessions was 10. Mean adherence during the month before the intervention was 75.7%, and increased significantly to 84.1% in the month after the first intervention session (p<0.001). The most frequently endorsed adherence barriers at session one were travel and forgetting. INTERPRETATION: A PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda and PrEP adherence increased after the intervention. Future research should identify PrEP users with low adherence for enhanced adherence counseling and determine optimal implementation strategies for interventions to maximize PrEP effectiveness. |
Recent patterns in population-based HIV prevalence in Swaziland
Bicego GT , Nkambule R , Peterson I , Reed J , Donnell D , Ginindza H , Duong YT , Patel H , Bock N , Philip N , Mao C , Justman J . PLoS One 2013 8 (10) e77101 BACKGROUND: The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs. METHODS: From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed. RESULTS: HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use. CONCLUSIONS: While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland. |
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