ABSTRACT
Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines.
Subject(s)
AIDS Vaccines , HIV Infections , HIV-1 , Humans , HIV Infections/diagnosis , HIV Infections/prevention & control , AIDS Vaccines/immunology , HIV-1/immunology , HIV Antibodies/blood , HIV Antibodies/immunology , Serologic Tests/methodsABSTRACT
BACKGROUND: Hepatitis C virus (HCV) screening is critical to HCV elimination efforts. Simplified diagnostics are required for low-resource settings and difficult-to-reach populations. This retrospective study assessed performance of rapid diagnostic tests (RDTs) for detection of HCV antibodies. METHODS: Two lots of 13 RDTs were evaluated at 3 laboratories using archived plasma samples from 4 countries (Nigeria, Georgia, Cambodia, and Belgium). HCV status was determined using 3 reference tests according to a composite algorithm. Sensitivity and specificity were evaluated in HIV-infected and HIV-uninfected populations. Operational characteristics were also assessed. RESULTS: In total, 1710 samples met inclusion criteria. In HIV-uninfected samples (nĆ¢ĀĀ =Ć¢ĀĀ 384), the majority of RDTs had sensitivity ≥98% in 1 or both lots and most RDTs had specificity ≥99%. In HIV-infected samples (nĆ¢ĀĀ =Ć¢ĀĀ 264), specificity remained high but sensitivity was markedly lower than in HIV-uninfected samples; only 1 RDT reached >95%. The majority of HIV-infected samples for which sensitivity was low did not have detectable HCV viral load/core antigen. Interreader variability, lot-to-lot variability, and rate of invalid runs were low for all RDTs (<2%). CONCLUSIONS: HCV RDTs should be evaluated in the intended target population, as sensitivity can be impacted by population factors such as HIV status. CLINICAL TRIALS REGISTRATION: NCT04033887.
Subject(s)
HIV Infections , Hepatitis C , Humans , Hepacivirus , Diagnostic Tests, Routine , Laboratories , Retrospective Studies , Hepatitis C/complications , Hepatitis C/diagnosis , Hepatitis C Antibodies , Sensitivity and Specificity , HIV Infections/epidemiologyABSTRACT
BACKGROUND: With a rapidly ageing society, healthy ageing has become a key challenge. Engagement in physical activity, and particularly walking, is a key strategy that contributes to healthy ageing amongst older adults. The purpose of the present study was to evaluate the efficacy of a group walking program for older adults that incorporates the 5R Shared Leadership Program (5RS). By implementing a structure of shared leadership and strengthening peer leaders' identity leadership, 5RS aims to cultivate a shared social identity amongst participants, which has in other contexts been associated with greater performance and well-being. METHODS: A cluster randomised controlled trial was conducted to test the efficacy of the 5RS group walking program on group identification, group cohesion, walking activity, and well-being, compared to a regular group walking program for older adults. Nineteen older adult walking groups (i.e., the clusters; N = 503; Mage = 69.23 years, SD = 6.68) all participated in a 12-week structured group walking program. Nine walking groups (n = 304) were randomly assigned to the intervention in which participants received the 5RS program in addition to regular group walking. RESULTS: 5RS was successful in strengthening the identity leadership qualities of the appointed peer leaders. Multilevel regressions showed that 5RS succeeded in increasing group cohesion and walking activity to a greater extent than a regular group walking program, while participants' group identification and well-being increased to a similar extent in both conditions. Furthermore, structural equation modelling revealed that group identification mediated the impact of peer leaders' identity leadership on group cohesion and well-being (but not walking activity). CONCLUSION: By harnessing the capacity of the group and its peer leaders, the 5RS program offers a promising intervention to engage older adults in physical activity. TRIAL REGISTRATION: The study was retrospectively registered as clinical trial on 9 September 2021 ( NCT05038423 ).
Subject(s)
Leadership , Walking , Aged , Exercise , Humans , Peer Group , Surveys and QuestionnairesABSTRACT
The social identity approach has become an important framework for understanding effective leadership. The present study is the first to longitudinally examine the relative impact of coaches' and athlete leaders' identity leadership on athletes' identification with their team, as well as the subsequent relationships with key team and individual outcomes. To investigate these research questions, 18 sport teams (N = 279) completed a questionnaire early and late in their season competition. To analyse these data, we conducted structural equation modelling and controlled both for baseline values and the nested structure of our data. Results revealed that it was mainly the identity leadership of athlete leaders (and not of the coach) early in the season that predicted athletes' team identification later in the season. This increased team identification in turn fed into both team outcomes (i.e., task climate, team resilience, team performance) and individual outcomes (i.e., well-being, burnout, and individual performance). The mediating role of team identification suggests that by building a shared sense of 'we', athlete leaders can improve the team's effectiveness and enhance athletes' well-being. Accordingly, we conclude that empowering athlete leaders and strengthening their identity leadership skills is an important way to unlock sport teams' full potential.
Subject(s)
Athletic Performance , Leadership , Humans , Motivation , Athletes , Social IdentificationABSTRACT
This retrospective study evaluated the reactivity of 3 human immunodeficiency virus (HIV) confirmatory assays (INNO-LIA, Geenius, and MP) and 7 HIV rapid tests on samples from 2 different study populations in Belgium. For the early-treated cohort (83 HIV-1 adult patients treated within 3 months after infection), HIV-1 diagnosis was not obtained in at least 1 confirmatory assay in 12.0% (10/83) and in an HIV rapid test in 31.3% (26/83). Confirmation assay sensitivities ranged from 87.5% to 95.2%, whereas rapid test assay sensitivities ranged from 75.9% to 100%. The time to treatment initiation or the length of time on treatment did not have a statistical influence on the probability to obtain a false-negative test result. The fastest reversion was demonstrated after 4 months of treatment. Among the long-term treated cohort (390 HIV-1 patients withĆ¢ĀĀ ≥Ć¢ĀĀ 9 years of undetectable viral load), false-negative test results were found in at least 1 HIV confirmatory assay for 2.1% (8/390) of the patients and in a HIV rapid test for 4.9% (19/390). Confirmation assay sensitivities ranged from 98.1% to 99.5%, whereas rapid test sensitivities ranged from 96.2% to 100%. Longer treatment increased nonreactivity of the HIV rapid tests (PĆ¢ĀĀ =Ć¢ĀĀ .033). Undetectable viral load decreases the sensitivities of HIV diagnostic tests, and further monitoring of the performance of serological assays is advised.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Diagnostic Tests, Routine/methods , HIV Infections/diagnosis , HIV Infections/drug therapy , Secondary Prevention/methods , Adult , Belgium , False Negative Reactions , HIV Antibodies , HIV-1 , Humans , Immunoassay , Retrospective Studies , Sensitivity and Specificity , Serologic Tests , Viral LoadABSTRACT
[This corrects the article DOI: 10.1371/journal.pbio.2001855.].
ABSTRACT
HIV-1 set-point viral load-the approximately stable value of viraemia in the first years of chronic infection-is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%-43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical "Brownian motion" model and another model ("Ornstein-Uhlenbeck") that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%-43%) is consistent with other studies based on regression of viral load in donor-recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.
Subject(s)
Genetic Variation , Genome, Viral , HIV Infections/microbiology , HIV Seropositivity/microbiology , HIV-1/genetics , Human Immunodeficiency Virus Proteins/genetics , Models, Genetic , Adult , Aged , Cohort Studies , Europe , Evolution, Molecular , Female , Genome-Wide Association Study , HIV Infections/blood , HIV Seropositivity/blood , HIV-1/growth & development , HIV-1/isolation & purification , HIV-1/pathogenicity , Human Immunodeficiency Virus Proteins/blood , Human Immunodeficiency Virus Proteins/metabolism , Humans , Male , Middle Aged , Phylogeny , Registries , Seroconversion , Viral Load , VirulenceABSTRACT
OBJECTIVES: An emerging body of evidence indicates that, in addition to the coach, athlete leaders within a team are vital for a sports team's success. Sports teams are therefore keen to know which attributes are distinctly characteristic of high-quality leaders on and off the field. The present study aims to shed more light on this question. METHOD: A wide variety of traits and leadership behaviors was assessed in a sample of 776 athletes, stratified across gender, competitive level, and four sports. The leadership quality of each of the athletes (ie, as task, motivational, social, and external leader) was determined on the basis of the perceptions of teammates using social network analysis. RESULTS: Findings revealed that leadership behaviors outweighed personality traits in distinguishing high-quality leaders from others on and off the field. Providing identity leadership that creates, embodies, advances, and embeds a collective sense of "us" in their teams was found to be a particularly important leadership behavior that characterized high-quality leaders both on and off the field. CONCLUSION: The fact that leadership behaviors were important predictors of high-quality athlete leadership (and more important predictors than traits) suggests that leaders are not just born, but can also be made. Our findings therefore highlight the clear need for leadership development programs to target the behaviors that we identified as important predictors of leadership.
Subject(s)
Athletes , Interpersonal Relations , Leadership , Motivation , Adolescent , Adult , Female , Humans , Male , Surveys and Questionnaires , Young AdultABSTRACT
Emotional contagion has been recognized as a variable influencing individual behaviour and team functioning. In particular, leaders within the team have been suggested to have a significant impact on their teammates through the expression of their emotions. As a result, the aim of this study was to provide greater insight into how different athlete leaders impact the emotional state of their team members, and whether gender differences existed in these relationships. Participants were 295 university student-athletes (200 male and 95 female) recruited from four universities in the UK. Data were collected in a two-step process. First, a voting/rating procedure was conducted within team to identify dominant task, motivational, social and external leaders. Then, participants completed the emotional contagion subscale of the Measure of Empathetic Tendency to rate the impact different athlete leaders had upon their emotional state. A MANOVA was conducted to explore gender differences in reported emotional susceptibility by leadership role. Subsequent ANOVAs highlighted significant differences between leadership role scores for female participants only. The results suggest that female athletes are more susceptible to emotional influence than male athletes. Furthermore, female athletes experienced a greater variation in the perceived emotional influence of different leadership roles in the team.
Subject(s)
Athletes/psychology , Competitive Behavior , Emotions , Leadership , Motivation , Athletic Performance/psychology , England , Female , Humans , Male , Sex Factors , Young AdultABSTRACT
BACKGROUND: In the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea. METHODS: In this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group. RESULTS: A total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed. CONCLUSIONS: The transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Union's Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).
Subject(s)
Blood Component Transfusion , Hemorrhagic Fever, Ebola/therapy , Plasma , Adolescent , Adult , Antibodies, Neutralizing/blood , Blood Component Transfusion/adverse effects , Child , Child, Preschool , Convalescence , Ebolavirus/immunology , Female , Guinea , Hemorrhagic Fever, Ebola/mortality , Humans , Infant , Male , Middle Aged , Odds Ratio , Plasma/immunology , Pregnancy , Young AdultABSTRACT
BACKGROUND: Sexually transmitted infections, such as HIV and syphilis, are one of the major health care problems worldwide, especially in low- and middle income countries. HIV screening programmes have been widely used for many years. The introduction of rapid point-of-care tests (RDTs) that can detect both HIV and syphilis, using one single blood specimen, would be a promising tool to integrate the detection of syphilis into HIV programmes and so improve the accessibility of syphilis testing and treatment. METHODS: As part of the World Health Organization pre-qualification of in vitro diagnostics assessment, the laboratory performance of four dual HIV-Syphilis rapid diagnostic tests (SD Bioline HIV/Syphilis Duo, DPP HIV-Syphilis Assay, Multiplo Rapid TP/HIV Antibody Test and Insti Multiplex HIV-1/HIV-2/Syphilis Antibody Test) was assessed using a well characterized multiregional panel of stored sera specimens. RESULTS: In total 400 specimens were tested with each assay, resulting in excellent sensitivities and specificities for HIV, ranging from 99.5 to 100% and from 93.5 to 99.5%, respectively. Results obtained for the Treponema pallidum antibodies were lower, with the lowest sensitivity of 73.5% for Multiplo and the highest of 87% for SD Bioline. Specificities ranged from 99.0 to 100%. CONCLUSION: Although these results suggest that the tests could further improve in accuracy in detection of treponemal antibodies, their introduction into screening programmes to increase the accessibility of HIV/Syphilis diagnosis and treatment for difficult to reach populations in the world is promising.
Subject(s)
Diagnostic Tests, Routine , HIV Infections/diagnosis , Syphilis/diagnosis , Antibodies, Bacterial/blood , HIV Antibodies/blood , HIV-1/immunology , HIV-2/immunology , Humans , Immunoassay , Laboratories , Mass Screening/methods , Point-of-Care Testing , Sensitivity and Specificity , Serologic Tests , Syphilis Serodiagnosis/methods , Treponema pallidum/immunologyABSTRACT
Based on the principles of the Social Identity Approach (SIA), the present experiment aimed to examine the impact of communicating descriptive age norms on older adults' autonomous motivation to exercise. Under the cover of a marketing study, older adults (n = 120; age = 65-70 years) participated in a newly created exercise activity, 'Pattern Stepping'. This activity was framed as an activity that was descriptively normative either for older adults, for younger adults, for both groups, or for none. Repeated measures ANOVAs revealed that participants felt greater satisfaction of their basic psychological needs and were more autonomously motivated to exercise if Pattern Stepping was framed as an activity popular among the young, rather than among older adults. These findings suggest that framing an exercise as descriptively normative for the elderly can thwart older adults' autonomous motivation if they do not identify as an older adult.
Subject(s)
Exercise/psychology , Health Promotion , Motivation , Social Identification , Aged , Female , Humans , MaleABSTRACT
PURPOSE: Grounded in the Cognitive Evaluation Theory, the present experiment aimed to compare the relative impact of competence support provided by coaches versus athlete leaders on players' competence satisfaction, intrinsic motivation, and performance. METHODS: We recruited 18 existing competitive male basketball teams (ie, 126 players) to participate in the experiment. Each team was randomly assigned to one of three conditions: (a) the coach provided competence support (ie, by encouraging, providing positive feedback, and expressing team confidence); (b) the athlete leader provided competence support; or (c) neither the coach, nor the athlete leader provided competence support (ie, control condition). RESULTS: Teams in which the athlete leader provided competence support reported higher levels of competence satisfaction and intrinsic motivation than teams in the control condition, a difference that did not emerge when the coach provided competence support. Furthermore, teams in which either the coach or the athlete leader supported team members' competence performed better compared to teams in the control group. CONCLUSION: Our findings highlight the importance of providing competence support to enhance team performance. Given athlete leaders' unique impact on teammates' competence satisfaction and motivation, instructing athlete leaders how to provide competence support constitutes an important motivational pathway for coaches to optimize team functioning.
Subject(s)
Athletes/psychology , Athletic Performance/psychology , Leadership , Motivation , Adolescent , Basketball , Belgium , Humans , Male , Personal Satisfaction , Random AllocationABSTRACT
In Flanders the term flandrien refers to cyclists who display a strong work ethic, great perseverance, are powerful and who perform best in adverse weather conditions. Until the 1960s, only leading cyclists originating from the province of West- and East-Flanders were considered as flandriens. After 1960, the media extended the use of this term to Belgian cyclists in general and even to international cyclists. The present study examined whether Flemish citizens agree with this generalization considering that the term flandrien still plays a highly symbolical role in the public discourse on Flemish identity. First, the main aim was to investigate whether having an ethno-cultural identity representation of the Flemish identity is positively related to perceived regional exclusivity of the term flandrien. Second, this study explored whether Flemish identification moderates this relation (i.e. this relation is only expected for high identifiers) and also predicts Flemings' regional exclusivity of the term. Results revealed that the more Flemings endorse an ethno-cultural identity representation the more they consider a flandrien as an exclusively Flemish cyclist, and the less they will include international cyclists in their consideration of a flandrien. Flemish identification did not moderate this relation but did predict the consideration of a flandrien as a Flemish cyclist. These findings indicate that the current interpretation of the historical cycling term flandrien is influenced by cultural conceptualizations of Flemish identity.
ABSTRACT
Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.
Subject(s)
Algorithms , Diagnostic Tests, Routine/methods , Enzyme-Linked Immunosorbent Assay/methods , HIV Infections/diagnosis , Mass Screening/methods , Africa South of the Sahara , Guidelines as Topic , Humans , Sensitivity and Specificity , World Health OrganizationABSTRACT
BACKGROUND: There is today no gold standard method to accurately define the time passed since infection at HIV diagnosis. Infection timing and incidence measurement is however essential to better monitor the dynamics of local epidemics and the effect of prevention initiatives. METHODS: Three methods for infection timing were evaluated using 237 serial samples from documented seroconversions and 566 cross sectional samples from newly diagnosed patients: identification of antibodies against the HIV p31 protein in INNO-LIA, SediaTM BED CEIA and SediaTM LAg-Avidity EIA. A multi-assay decision tree for infection timing was developed. RESULTS: Clear differences in recency window between BED CEIA, LAg-Avidity EIA and p31 antibody presence were observed with a switch from recent to long term infection a median of 169.5, 108.0 and 64.5Ā days after collection of the pre-seroconversion sample respectively. BED showed high reliability for identification of long term infections while LAg-Avidity is highly accurate for identification of recent infections. Using BED as initial assay to identify the long term infections and LAg-Avidity as a confirmatory assay for those classified as recent infection by BED, explores the strengths of both while reduces the workload. The short recency window of p31 antibodies allows to discriminate very early from early infections based on this marker. BED recent infection results not confirmed by LAg-Avidity are considered to reflect a period more distant from the infection time. False recency predictions in this group can be minimized by elimination of patients with a CD4 count of less than 100 cells/mm3 or without no p31 antibodies. For 566 cross sectional sample the outcome of the decision tree confirmed the infection timing based on the results of all 3 markers but reduced the overall cost from 13.2 USD to 5.2 USD per sample. CONCLUSIONS: A step-wise multi assay decision tree allows accurate timing of the HIV infection at diagnosis at affordable effort and cost and can be an important new tool in studies analyzing the dynamics of local epidemics or the effects of prevention strategies.
Subject(s)
Decision Trees , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Seropositivity/diagnosis , Adult , Belgium/epidemiology , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Antigens/immunology , HIV Infections/drug therapy , HIV-1/immunology , HIV-1/pathogenicity , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Reproducibility of Results , Time FactorsABSTRACT
Two studies investigated the structure of different athlete leadership networks and its relationship to cohesion using social network analysis. In Study 1, we examined the relationship between a general leadership quality network and task and social cohesion as measured by the Group Environment Questionnaire (GEQ). In Study 2, we investigated the leadership networks for four different athlete leadership roles (task, motivational, social and external) and their association with task and social cohesion networks. In Study 1, the results demonstrated that the general leadership quality network was positively related to task and social cohesion. The results from Study 2 indicated positive correlations between the four leadership networks and task and social cohesion networks. Further, the motivational leadership network emerged as the strongest predictor of the task cohesion network, while the social leadership network was the strongest predictor of the social cohesion network. The results complement a growing body of research indicating that athlete leadership has a positive association with cohesion.
Subject(s)
Group Processes , Interpersonal Relations , Leadership , Motivation , Social Behavior , Sports , Adolescent , Adult , Basketball , Female , Humans , Male , Soccer , Social Support , Surveys and Questionnaires , Volleyball , Young AdultABSTRACT
BACKGROUND: Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety. RESULTS: HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS: Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).
Subject(s)
Adenine/analogs & derivatives , Anti-Retroviral Agents/therapeutic use , Deoxycytidine/analogs & derivatives , HIV Infections/prevention & control , HIV-1 , Organophosphonates/therapeutic use , Adenine/adverse effects , Adenine/therapeutic use , Adolescent , Adult , Alanine Transaminase/blood , Anti-Retroviral Agents/adverse effects , Case-Control Studies , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Double-Blind Method , Drug Combinations , Drug Resistance, Viral , Emtricitabine , Female , HIV Infections/epidemiology , HIV Seropositivity , HIV-1/genetics , HIV-1/isolation & purification , Humans , Incidence , Kaplan-Meier Estimate , Medication Adherence , Organophosphonates/adverse effects , RNA, Viral/blood , Risk-Taking , Sexual Behavior/statistics & numerical data , Tenofovir , Treatment Failure , Viral Load , Young AdultABSTRACT
BACKGROUND: Non-B subtypes account for at least 50 % of HIV-1 infections diagnosed in Belgium and Luxembourg. They are considered to be acquired through heterosexual contacts and infect primarily individuals of foreign origin. Information on the extent to which non-B subtypes spread to the local population is incomplete. METHODS: Pol and env gene sequences were collected from 410 non-subtype B infections. Profound subtyping was performed using 5 subtyping tools and sequences of both pol and env. Demographic information, disease markers (viral load, CD4 count) and viral characteristics (co-receptor tropism) were compared between subtypes. Maximum likelihood phylogenetic trees were constructed and examined for clustering. RESULTS: The majority of non-B infections were diagnosed in patients originating from Africa (55.8 %), individuals born in Western Europe represented 30.5 %. Heterosexual transmission was the most frequently reported transmission route (79.9 %), MSM transmission accounted for 12.2 % and was significantly more frequently reported for Western Europeans (25.7 % versus 4.3 % for individuals originating from other regions; p < 0.001). Subtypes A and C and the circulating recombinant forms CRF01_AE and CRF02_AG were the most represented and were included in the comparative analysis. Native Western Europeans were underrepresented for subtype A (14.5 %) and overrepresented for CRF01_AE (38.6 %). The frequency of MSM transmission was the highest for CRF01_AE (18.2 %) and the lowest for subtype A (0 %). No differences in age, gender, viral load or CD4 count were observed. Prevalence of CXCR4-use differed between subtypes but largely depended on the tropism prediction algorithm applied. Indications for novel intersubtype recombinants were found in 20 patients (6.3 %). Phylogenetic analysis revealed only few and small clusters of local transmission but could document one cluster of CRF02_AG transmission among Belgian MSM. CONCLUSIONS: The extent to which non-B subtypes spread in the native Belgian-Luxembourg population is higher than expected, with 30.5 % of the non-B infections diagnosed in native Western Europeans. These infections resulted from hetero- as well as homosexual transmission. Introduction of non-B variants in the local high at risk population of MSM may lead to new sub-epidemics and/or increased genetic variability and is an evolution that needs to be closely monitored.
Subject(s)
HIV Infections/epidemiology , HIV Infections/transmission , HIV-1/genetics , Transients and Migrants , Adult , Africa , Belgium/epidemiology , CD4 Lymphocyte Count , Cluster Analysis , Europe , Female , HIV-1/pathogenicity , Heterosexuality , Humans , Luxembourg/epidemiology , Male , Phylogeny , Receptors, CXCR4 , Retrospective Studies , env Gene Products, Human Immunodeficiency Virus/genetics , pol Gene Products, Human Immunodeficiency Virus/geneticsABSTRACT
BACKGROUND: As HIV remains a public health concern, increased testing among those at risk for HIV acquisition is important. Men who have sex with men (MSM) are the most important group for targeted HIV testing in Europe. Several new strategies have been developed and implemented to increase HIV-testing uptake in this group, among them the Swab2know project. OBJECTIVE: In this project, we aim to assess the acceptability and feasibility of outreach and online HIV testing using oral fluid samples as well as Web-based delivery of test results. METHODS: Sample collection happened between December 2012 and April 2014 via outreach and online sampling among MSM. Test results were communicated through a secured website. HIV tests were executed in the laboratory. Each reactive sample needed to be confirmed using state-of-the-art confirmation procedures on a blood sample. Close follow-up of participants who did not pick up their results, and those with reactive results, was included in the protocol. Participants were asked to provide feedback on the methodology using a short survey. RESULTS: During 17 months, 1071 tests were conducted on samples collected from 898 men. Over half of the samples (553/1071, 51.63%) were collected during 23 outreach sessions. During an 8-month period, 430 samples out of 1071 (40.15%) were collected from online sampling. Additionally, 88 samples out of 1071 (8.22%) were collected by two partner organizations during face-to-face consultations with MSM and male sex workers. Results of 983 out of 1071 tests (91.78%) had been collected from the website. The pickup rate was higher among participants who ordered their kit online (421/430, 97.9%) compared to those participating during outreach activities (559/641, 87.2%; P<.001). MSM participating during outreach activities versus online participants were more likely to have never been tested before (17.3% vs 10.0%; P=.001) and reported more sexual partners in the 6 months prior to participation in the project (mean 7.18 vs 3.23; P<.001). A total of 20 participants out of 898 (2.2%) were confirmed HIV positive and were linked to care. Out of 1071 tests, 28 (2.61%) with a weak reactive result could not be confirmed, and were thereby classified as false reactive results. Most of the 388 participants who completed posttest surveys (388/983, 39.5%) were very positive about their experience. The vast majority (371/388, 95.6%) were very satisfied, while 17 out of 388 (4.4%) reported mixed feelings. CONCLUSIONS: Despite a high yield and a considerable number of false reactive results, satisfaction was high among participants. The project helped us to reach the target population, both in numbers of tests executed and in newly diagnosed HIV infections. Further optimization should be considered in the accuracy of the test, the functionalities of the website (including an online counseling tool), and in studying the cost effectiveness of the methodology.