Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Robb L [original query] |
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Single and combined effects of multiple intensities of behavioral modification and methylphenidate for children with ADHD in the home setting
Merrill BM , Macphee FL , Burrows-MacLean L , Coles EK , Wymbs BT , Chacko A , Walker K , Wymbs F , Garefino A , Robb Mazzant J , Gnagy EM , Waxmonsky JG , Massetti GM , Waschbusch DA , Fabiano GA , Pelham WE Jr . Res Child Adolesc Psychopathol 2023 51 (10) 1481-1495 Behavioral treatment, stimulants, and their combination are the recommended treatments for childhood attention-deficit/hyperactivity disorder (ADHD). The current study utilizes within-subjects manipulations of multiple doses of methylphenidate (placebo, 0.15, 0.30, and 0.60 mg/kg/dose t.i.d.) and intensities of behavioral modification (no, low, and high intensity) in the summer treatment program (STP) and home settings. Outcomes are evaluated in the home setting. Participants were 153 children (ages 5-12) diagnosed with ADHD. In alignment with experimental conditions implemented during the STP day, parents implemented behavioral modification levels in three-week intervals, child medication status varied daily, and the orders were randomized. Parents provided daily reports of child behavior, impairment, and symptoms and self-reported parenting stress and self-efficacy. At the end of the study, parents reported treatment preferences. Stimulant medication led to significant improvements across all outcome variables with higher doses resulting in greater improvement. Behavioral treatment significantly improved child individualized goal attainment, symptoms, and impairment in the home setting and parenting stress and self-efficacy. Effect sizes indicate that behavioral treatment combined with a low-medium dose (0.15 or 0.30 mg/kg/dose) of medication results in equivalent or superior outcomes compared to a higher dose (0.60 mg/kg/dose) of medication alone. This pattern was seen across outcomes. Parents overwhelmingly reported preferring treatment with a behavioral component as a first-choice treatment (99%). Results underscore the need to consider dosing as well as parent preference when utilizing combined treatment approaches. This study provides further evidence that combining behavioral treatment and stimulant medication may reduce the stimulant dose needed for beneficial effects. |
HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype.
Li SS , Hickey A , Shangguan S , Ehrenberg PK , Geretz A , Butler L , Kundu G , Apps R , Creegan M , Clifford RJ , Pinyakorn S , Eller LA , Luechai P , Gilbert PB , Holtz TH , Chitwarakorn A , Sacdalan C , Kroon E , Phanuphak N , de Souza M , Ananworanich J , O'Connell RJ , Robb ML , Michael NL , Vasan S , Thomas R . Cell Host Microbe 2022 30 (8) 1173-1185 e8 Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia. |
Development of HEK-293 cell lines constitutively expressing flaviviral antigens for use in diagnostics
Powers JA , Skinner B , Davis BS , Biggerstaff BJ , Robb L , Gordon E , Calvert AE , Chang GJ . Microbiol Spectr 2022 10 (3) e0059222 Flaviviruses are important human pathogens worldwide. Diagnostic testing for these viruses is difficult because many of the pathogens require specialized biocontainment. To address this issue, we generated 39 virus-like particle (VLP)- and nonstructural protein 1 (NS1)-secreting stable cell lines in HEK-293 cells of 13 different flaviviruses, including dengue, yellow fever, Japanese encephalitis, West Nile, St. Louis encephalitis, Zika, Rocio, Ilheus, Usutu, and Powassan viruses. Antigen secretion was stable for at least 10 cell passages, as measured by enzyme-linked immunosorbent assays and immunofluorescence assays. Thirty-five cell lines (90%) had stable antigen expression over 10 passages, with three of these cell lines (7%) increasing in antigen expression and one cell line (3%) decreasing in antigen expression. Antigen secretion in the HEK-293 cell lines was higher than in previously developed COS-1 cell line counterparts. These antigens can replace current antigens derived from live or inactivated virus for safer use in diagnostic testing. IMPORTANCE Serological diagnostic testing for flaviviral infections is hindered by the need for specialized biocontainment for preparation of reagents and assay implementation. The use of previously developed COS-1 cell lines secreting noninfectious recombinant viral antigen is limited due to diminished antigen secretion over time. Here, we describe the generation of 39 flaviviral virus-like particle (VLP)- and nonstructural protein 1 (NS1)-secreting stable cell lines in HEK-293 cells representing 13 medically important flaviviruses. Antigen production was more stable and statistically higher in these newly developed cell lines than in their COS-1 cell line counterparts. The use of these cell lines for production of flaviviral antigens will expand serological diagnostic testing of flaviviruses worldwide. |
Improving reporting standards for polygenic scores in risk prediction studies.
Wand H , Lambert SA , Tamburro C , Iacocca MA , O'Sullivan JW , Sillari C , Kullo IJ , Rowley R , Dron JS , Brockman D , Venner E , McCarthy MI , Antoniou AC , Easton DF , Hegele RA , Khera AV , Chatterjee N , Kooperberg C , Edwards K , Vlessis K , Kinnear K , Danesh JN , Parkinson H , Ramos EM , Roberts MC , Ormond KE , Khoury MJ , Janssens Acjw , Goddard KAB , Kraft P , MacArthur JAL , Inouye M , Wojcik GL . Nature 2021 591 (7849) 211-219 Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice. |
Variation in E. coli concentrations in open drains across neighborhoods in Accra, Ghana: The influence of onsite sanitation coverage and interconnectedness of urban environments
Berendes DM , de Mondesert L , Kirby AE , Yakubu H , Adomako L , Michiel J , Raj S , Robb K , Wang Y , Doe B , Ampofo J , Moe CL . Int J Hyg Environ Health 2020 224 113433 Alongside efforts to improve safe management of feces along the entire sanitation chain, including after the toilet, global sanitation efforts are focusing on universal access ‘basic’ services: onsite facilities that safely contain excreta away from human contact. Although fecal sludge management is improving in urban areas, open drains remain a common fate for feces in these often densely-populated neighborhoods in low-income countries. To-date, it is unclear to what extent complete coverage of onsite sanitation reduces fecal contamination in the urban environment and how fecal contamination varies within urban drains across neighborhoods by sanitation status within a city. We assessed how neighborhood levels of environmental fecal contamination (via spatially-representative sampling of open drains for E. coli) varied across four neighborhoods with varying income, type and coverage of household sanitation facilities, and population density in Accra, Ghana. Neighborhoods with very high sanitation coverage (≥89%) still had high (>4 log10 CFU/100 mL) E. coli concentrations in drains. Between-neighborhood variation in E. coli levels among the high coverage neighborhoods was significant: drain concentrations in neighborhoods with 93% and 89% coverage (4.7 (95% CI: 4.5, 4.9) & 4.9 (95% CI: 4.5, 5.3) log10 CFU/100 mL, respectively) were higher than in the neighborhood with 97% coverage (4.1 log10 CFU/100 mL, 95% CI: 3.8, 4.4 log10 CFU/100 mL). Compared with the highest coverage neighborhood, the neighborhood with lowest coverage (48%) also had higher E. coli concentrations (5.6 log10 CFU/100 mL, 95% CI: 5.3, 5.9 log10 CFU/100 mL). Although fecal contamination in open drains appeared lower in neighborhoods with higher onsite sanitation coverage (and vice versa), other factors (e.g. fecal sludge management, animals, population density) may affect drain concentrations. These results underscore that neighborhood-level onsite sanitation improvements alone may not sufficiently reduce fecal hazards to public health from open drains. These findings supporting the need for integrated, city-level fecal sludge management alongside multifaceted interventions to reduce fecal contamination levels and human exposure. |
Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial.
Pantaleo G , Janes H , Karuna S , Grant S , Ouedraogo GL , Allen M , Tomaras GD , Frahm N , Montefiori DC , Ferrari G , Ding S , Lee C , Robb ML , Esteban M , Wagner R , Bart PA , Rettby N , McElrath MJ , Gilbert PB , Kublin JG , Corey L . Lancet HIV 2019 6 (11) e737-e749 BACKGROUND: Up to now, immunisation regimens that have been assessed for development of HIV vaccines have included purified envelope (Env) protein among the boosting components of the regimen. We postulated that co-administration of Env protein with either a DNA or NYVAC vector during priming would result in early generation of antibody responses to the Env V1/V2 region, which are important markers for effective protection against infection. We aimed to assess the safety and immunogenicity of a multivalent HIV vaccine including either DNA or NYVAC vectors alone or in combination with Env glycoprotein (gp120) followed by a co-delivered NYVAC and Env protein boost. METHODS: We did a single-centre, double-blind, placebo-controlled phase 1b trial at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). We included healthy volunteers aged 18-50 years who were at low risk of HIV infection. We randomly allocated participants using computer-generated random numbers to one of four vaccination schedules or placebo (4:1), and within these schedules participants were allocated either active treatment (T1, T2, T3, and T4) or placebo (C1, C2, C3, and C4). T1 consisted of two doses of NYVAC vector followed by two doses of NYVAC vector and gp120 Env protein; T2 comprised four doses of NYVAC vector and gp120 Env protein; T3 was two doses of DNA vector followed by two doses of NYVAC vector and gp120 Env protein; and T4 was two doses of DNA vector and gp120 Env protein followed by two doses of NYVAC vector and gp120 Env protein. Placebo injections were matched to the corresponding active treatment group. Doses were administered by injection at months 0, 1, 3, and 6. Primary outcomes were safety and immunogenicity of the vaccine schedules. Immune response measures included cross-clade and epitope-specific binding antibodies, neutralising antibodies, and antibody-dependent cell-mediated cytotoxicity measured 2 weeks after the month 1, 3, and 6 vaccinations. This trial is registered with ClinicalTrials.gov, NCT01799954. FINDINGS: Between Aug 23, 2012, and April 18, 2013, 148 healthy adult volunteers were screened for the trial, of whom 96 participants were enrolled. 20 individuals were allocated to each active treatment group (groups T1-4; n=80) and four were assigned to each placebo group (groups C1-4; n=16). Vaccines containing the NYVAC vector (groups T1 and T2) were associated with more frequent severe reactogenicity and more adverse events than were vaccines containing the DNA vector (groups T3 and T4). The most frequent adverse events judged related to study product were lymphadenopathy (n=9) and hypoaesthesia (n=2). Two participants, one in the placebo group and one in the DNA-primed T3 group, had serious adverse events that were judged unrelated to study product. One participant in the T3 group died from cranial trauma after a motor vehicle accident. Across the active treatment groups, IgG responses 2 weeks after the 6-month dose of vaccine were 74-95%. Early administration of gp120 Env protein (groups T2 and T4) was associated with a substantially earlier and higher area under the curve for gp120 Env binding, production of anti-V1/V2 and neutralising antibodies, and better antibody-response coverage over a period of 18 months, compared with vaccination regimens that delayed administration of gp120 Env protein until the 3-month vaccination (groups T1 and T3). INTERPRETATION: Co-administration of gp120 Env protein components with DNA or NYVAC vectors during priming led to early and potent induction of Env V1/V2 IgG binding antibody responses. This immunisation approach should be considered for induction of preventive antibodies in future HIV vaccine efficacy trials. FUNDING: National Institutes of Health, National Institute of Allergy and Infectious Diseases, and the Bill & Melinda Gates Foundation. |
U.S. Transportation and Health Tool: Data for action
Boehmer TK , Wendel AM , Bowers F , Robb K , Christopher E , Broehm JE , Rose K , Ralph J . J Transp Health 2017 6 530-537 Transportation investments have the potential to improve health, but readily available data to guide transportation decisions that could promote health are limited. In October 2015, the U.S. Department of Transportation (USDOT) and the Centers for Disease Control and Prevention (CDC) released the Transportation and Health Tool (THT). The tool is a resource to help transportation professionals in states and metropolitan areas access data about transportation and health in their jurisdictions and stimulate discussions on how to improve public health through transportation planning and policy. To develop the tool, a multidisciplinary team identified 190 possible data indicators. Using input from expert panel workshops and criteria that addressed data availability, geographic scale, timeliness, feasibility, validity, and topic area, the team selected 14 transportation and health indicators that covered the four priority topic areas of safety, active transportation, air quality, and connectivity. The THT contains the raw values for each indicator and a standardized score to enable comparisons. Additionally, the THT contains 25 evidence-based strategies that can help practitioners in states and metropolitan areas take action to improve health outcomes. |
Home blood pressure monitoring among adults-American Heart Association Cardiovascular Health Consumer Survey, 2012
Ayala C , Tong X , Neeley E , Lane R , Robb K , Loustalot F . J Clin Hypertens (Greenwich) 2017 19 (6) 584-591 Home blood pressure monitoring (HBPM) among hypertensive adults was assessed using the 2012 American Heart Association Cardiovascular Health Consumer Survey. The prevalence of hypertension was 25.5% and 53.8% of those reported HBPM. Approximately 63% of hypertensive adults 65 years and older reported HBPM followed by 51% and 34.6% (35-64 and 18-34 years, respectively; P=.001). Those who had seen a healthcare professional within a year reported HBPM compared with those who had not (54.8% vs 32.8%, P=.047). Those who believed that lowering blood pressure can reduce risk of heart attack and stroke had a higher percentage of HBPM compared with those who did not (55.5% vs 33.1%, P=.01). Age and the belief that lowering blood pressure could reduce cardiovascular disease risk were significant factors associated with HBPM. Half of the adult hypertensive patients reported HBPM and its use was greater among those who reported a positive attitude toward lowering blood pressure to reduce cardiovascular disease risk. |
Transforming evidence generation to support health and health care decisions
Califf RM , Robb MA , Bindman AB , Briggs JP , Collins FS , Conway PH , Coster TS , Cunningham FE , De Lew N , DeSalvo KB , Dymek C , Dzau VJ , Fleurence RL , Frank RG , Gaziano JM , Kaufmann P , Lauer M , Marks PW , McGinnis JM , Richards C , Selby JV , Shulkin DJ , Shuren J , Slavitt AM , Smith SR , Washington BV , White PJ , Woodcock J , Woodson J , Sherman RE . N Engl J Med 2016 375 (24) 2395-2400 Making better choices about health and health care requires the best possible evidence. Unfortunately, many of the decisions made today in our health care system are not supported by high-quality evidence1-4 derived from randomized, controlled trials or well-designed observational studies. But as rich, diverse sources of digital data become widely available for research and as analytical tools continue to grow in power and sophistication, the research and health care communities now have the opportunity to quickly and efficiently generate the scientific evidence needed to support improved decision making about health and health care. | The pursuit of high-quality, data-driven evidence in no way detracts from the importance of expert opinion and qualitative information as a complementary source of knowledge to inform policy decisions or population and individual choices; in fact, it enhances it. However, we believe there is an opportunity to use qualitative methods to supplement high-quality quantitative data with a more focused approach. |
Out-of-hospital cardiac arrest surveillance --- Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005--December 31, 2010
McNally B , Robb R , Mehta M , Vellano K , Valderrama AL , Yoon PW , Sasson C , Crouch A , Perez AB , Merritt R , Kellermann A . MMWR Surveill Summ 2011 60 (8) 1-19 PROBLEM/CONDITION: Each year, approximately 300,000 persons in the United States experience an out-of-hospital cardiac arrest (OHCA); approximately 92% of persons who experience an OHCA event die. An OHCA is defined as cessation of cardiac mechanical activity that occurs outside of the hospital setting and is confirmed by the absence of signs of circulation. Whereas an OHCA can occur from noncardiac causes (i.e., trauma, drowning, overdose, asphyxia, electrocution, primary respiratory arrests, and other noncardiac etiologies), the majority (70%--85%) of such events have a cardiac cause. The majority of persons who experience an OHCA event, irrespective of etiology, do not receive bystander-assisted cardiopulmonary resuscitation (CPR) or other timely interventions that are known to improve the likelihood of survival to hospital discharge (e.g., defibrillation). Because nearly half of cardiac arrest events are witnessed, efforts to increase survival rates should focus on timely and effective delivery of interventions by bystanders and emergency medical services (EMS) personnel. This is the first report to provide summary data from an OHCA surveillance registry in the United States. REPORTING PERIOD: This report summarizes surveillance data collected during October 1, 2005-- December 31, 2010. DESCRIPTION OF THE SYSTEM: In 2004, CDC established the Cardiac Arrest Registry to Enhance Survival (CARES) in collaboration with the Department of Emergency Medicine at the Emory University School of Medicine. This registry evaluates only OHCA events of presumed cardiac etiology that involve persons who received resuscitative efforts, including CPR or defibrillation. Participating sites collect data from three sources that define the continuum of emergency cardiac care: 911 dispatch centers, EMS providers, and receiving hospitals. OHCA is defined in CARES as a cardiac arrest that occurred in the prehospital setting, had a presumed cardiac etiology, and involved a person who received resuscitative efforts, including CPR or defibrillation. RESULTS: During October 1, 2005--December 31, 2010, a total of 40,274 OHCA records were submitted to the CARES registry. After noncardiac etiology arrests and missing hospital outcomes were excluded from the analysis (n = 8,585), 31,689 OHCA events of presumed cardiac etiology (e.g., myocardial infarction or arrhythmia) that received resuscitation efforts in the prehospital setting were analyzed. The mean age at cardiac arrest was 64.0 years (standard deviation [SD]: 18.2); 61.1% of persons who experienced OHCA were male (n = 19,360). According to local EMS agency protocols, 21.6% of patients were pronounced dead after resuscitation efforts were terminated in the prehospital setting. The survival rate to hospital admission was 26.3%, and the overall survival rate to hospital discharge was 9.6%. Approximately 36.7% of OHCA events were witnessed by a bystander. Only 33.3% of all patients received bystander CPR, and only 3.7% were treated by bystanders with an automated external defibrillator (AED) before the arrival of EMS providers. The group most likely to survive an OHCA are persons who are witnessed to collapse by a bystander and found in a shockable rhythm (e.g., ventricular fibrillation or pulseless ventricular tachycardia). Among this group, survival to discharge was 30.1%. A subgroup analysis was performed among persons who experienced OHCA events that were not witnessed by EMS personnel to evaluate rates of bystander CPR for these persons. After exclusion of 3,400 OHCA events that occurred after the arrival of EMS providers, bystander CPR information was analyzed for 28,289 events. In this group, whites were significantly more likely to receive CPR than blacks, Hispanics, or members of other racial/ethnic populations (p<0.001). Overall survival to hospital discharge of patients whose events were not witnessed by EMS personnel was 8.5%. Of these, patients who received bystander CPR had a significantly higher rate of overall survival (11.2%) than those who did not (7.0%) (p<0.001). INTERPRETATION: CARES data have helped identify opportunities for improvement in OHCA care. The registry is being used continually to monitor prehospital performance and selected aspects of hospital care to improve quality of care and increase rates of survival following OHCA. CARES data confirm that patients who receive CPR from bystanders have a greater chance of surviving OHCA than those who do not. PUBLIC HEALTH ACTIONS: Medical directors and public health professionals in participating communities use CARES data to measure and improve the quality of prehospital care for persons experiencing OHCA. Tracking performance longitudinally allows communities to better understand which elements of their care are working well and which elements need improvement. Education of public officials and community members about the importance of increasing rates of bystander CPR and promoting the use of early defibrillation by lay and professional rescuers is critical to increasing survival rates. Reporting at the state and local levels can enable state and local public health and EMS agencies to coordinate their efforts to target improving emergency response for OHCA events, regardless of etiology, which can lead to improvement in OHCA survival rates. |
Risk factors for HIV-1 infection in a longitudinal, prospective cohort of adults from the Mbeya Region, Tanzania
Geis S , Maboko L , Saathoff E , Hoffmann O , Geldmacher C , Mmbando D , Samky E , Michael NL , Birx DL , Robb ML , Hoelscher M . J Acquir Immune Defic Syndr 2011 56 (5) 453-9 BACKGROUND: To control the global HIV epidemic targeted interventions to reduce the incidence of HIV infections are urgently needed until an effective HIV vaccine is available. This study describes HIV-1 incidence and associated risk factors in a general population cohort of adults from Mbeya Region, Tanzania, who participated in a vaccine preparedness study. METHODS: We conducted a closed prospective cohort study with six-monthly follow-up from 2002-2006, enrolling adults from the general population. HIV-1 incidence and risk factors for HIV-1 acquisition were analysed using Cox regression. RESULTS: We observed 2,578 sero-negative participants for a mean period of 3.06 PY (7,471 PY in total). Overall HIV-1 incidence was 1.35 per 100 PY (95% confidence interval [CI]=1.10-1.64/100 PY). The highest overall HIV-1 incidence was found in females from Itende village (1.55 per 100 PY, 95%CI=0.99-2.30/100 PY), the highest age-specific incidence was observed in semi-urban males aged 30-34 years (2.75 per 100 PY, 95%CI=0.75-7.04). HIV-1 acquisition was independently associated with female gender (hazard ratio [HR]=1.64, 95%CI=1.05-2.57), younger age at enrolment (age 18-19 vs. 35-39: HR=0.29, 95%CI=0.11-0.75), alcohol consumption (almost daily vs. none: HR 2.01, 95%CI=1.00-4.07), education level (secondary school vs. none: HR 0.39, 95%CI=0.17-0.89) and number of lifetime sex partners (more than five vs. one: HR 2.22, 95%CI=1.13-4.36). CONCLUSIONS: A high incidence of HIV was observed in this cohort, and incident infection was strongly associated with young age, alcohol consumption, low school education level and number of sex partners. Targeted interventions are needed to address the elevated risk associated with these factors. |
A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-uninfected East Africans (RV 172)
Kibuuka H , Kimutai R , Maboko L , Sawe F , Schunk MS , Kroidl A , Shaffer D , Eller LA , Kibaya R , Eller MA , Schindler KB , Schuetz A , Millard M , Kroll J , Dally L , Hoelscher M , Bailer R , Cox JH , Marovich M , Birx DL , Graham BS , Michael NL , de Souza MS , Robb ML . J Infect Dis 2010 201 (4) 600-7 BACKGROUND: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. METHODS: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. RESULTS: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). CONCLUSION: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 . |
Short communication: HIV type 1 genetic diversity among tea plantation workers in Kericho, Kenya
Arroyo MA , Sateren WB , Foglia G , Kibaya R , Langat L , Wasunna M , Bautista CT , Scott PT , Shaffer DN , Robb ML , Michael NL , Birx DL , McCutchan FE . AIDS Res Hum Retroviruses 2009 25 (11) 1061-4 In preparation for HIV-1 vaccine trials in Kenya, 2801 study volunteers, from a tea plantation in Kericho, were recruited as part of a prospective vaccine cohort development study. Cryopreserved plasma was available from 401 HIV-positive volunteers, and was the source of viral RNA for genotyping by the multiregion hybridization assay (MHA). Logistic regression was performed to determine association of risk factors and HIV-1 recombinant and dual infections. At baseline, HIV-1 subtype A was the dominant circulating pure subtype (56%), followed by subtype D (10%) and C (5%). Recombinant HIV-1 strains accounted for almost one-third of all infections (29%), with 7% infected with a dual strain of the HIV-1 variants described. A higher number of HIV-1 recombinant and dual infections was observed among volunteers who were 18-24 and 25-29 years of age, affiliated with the Luo tribe, had been married two or more times, reported not being circumcised, and had STI symptoms in the past 6 months. Adjusted odds ratios (AOR) significantly associated with HIV-1 recombinant and dual infection were age difference from current spouse (5-9 years; AOR = 2.5, 95% CI = 1.2-5.3 and > or = 10 years; AOR = 3.1, 95% CI = 1.5-6.4) and reported STI symptoms in the past 6 months (AOR = 4.8, 95% CI = 2.0-11.6), respectively. In conclusion, our results suggest that there is considerable heterogeneity with respect to HIV-1 subtype diversity in this population that should be considered in the planning for future vaccine trials in the region. |
HIV-1 incidence rates and risk factors in agricultural workers and dependents in rural Kenya: 36-month follow-up of the Kericho HIV cohort study
Shaffer DN , Ngetich IK , Bautista CT , Sawe FK , Renzullo PO , Scott PT , Kibaya RM , Imbuki KO , Michael NL , Birx DL , Wasunna MK , Robb ML . J Acquir Immune Defic Syndr 2009 53 (4) 514-21 BACKGROUND: Incidence data from prospective cohort studies using rigorous laboratory methods are important in designing and evaluating HIV vaccine and therapeutic clinical trials and health care programs. We report 36-month HIV-1 incidence rates and demographic and psychosocial risks from the Kericho cohort in rural Kenya's southern Rift Valley Province. METHODS: Thirty-six month, prospective, closed, observational cohort study of adult plantation workers and dependents followed biannually. HIV-1 incidence rates per 100 person-years (py) were calculated, and Cox regression analyses were used to estimate hazards ratios (HR) associated with seroconversion. RESULTS: Two thousand four hundred volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated. Twenty-nine new HIV cases were identified in year 1 of follow-up, which increased to cumulative totals of 49 and 63 cases in years 2 and 3, respectively. The corresponding 1-, 2-, and 3-year incidence rates were 1.41 [95% confidence interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00 (95% CI = 0.77-1.28) per 100 py. Risk factors associated with HIV seroconversion included the following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than once (HR = 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32; 95% CI = 0.17-0.60), history of sexually transmitted infection (HR = 2.40; 95% CI = 1.09-5.26), history of substance abuse during sex (HR = 2.44; 95% CI = 1.16-5.13), and history of transactional sex (HR = 3.30; 95% CI = 1.79-6.09). CONCLUSIONS: HIV-1 incidence rates were relatively low in adult plantation workers and dependents in rural Kenya. Cohorts including higher risk populations (eg, commercial sex workers) warrant consideration for regional HIV preventive vaccine trials. Even low incidence, well-described cohorts generate valuable epidemiological clinical trial data. |
Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand
Rerks-Ngarm S , Pitisuttithum P , Nitayaphan S , Kaewkungwal J , Chiu J , Paris R , Premsri N , Namwat C , de Souza M , Adams E , Benenson M , Gurunathan S , Tartaglia J , McNeil JG , Francis DP , Stablein D , Birx DL , Chunsuttiwat S , Khamboonruang C , Thongcharoen P , Robb ML , Michael NL , Kunasol P , Kim JH , MOPH-TAVEG Investigators . N Engl J Med 2009 361 (23) 2209-20 BACKGROUND: The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control. METHODS: In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years. RESULTS: In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], -4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,452 subjects, the vaccine efficacy was 26.2% (95% CI, -13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 51.2; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. CONCLUSIONS: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.) Copyright 2009 Massachusetts Medical Society. |
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