Standardised method for reporting exercise programmes : protocol for a modified Delphi study

Introduction Exercise is integral to health across the lifespan and important for people with chronic health conditions. A systematic review of exercise trials for chronic conditions reported suboptimal descriptions of the evaluated interventions and concluded that this hinders interpretation and replication. The aim of this project is to develop a standardised method for reporting essential exercise programme details being evaluated in clinical trials. Methods and analysis A modified Delphi technique will be used to gain consensus among international exercise experts. We will use three sequential rounds of anonymous online questionnaires to refine a standardised checklist. A draft checklist of potentially relevant items was developed based on the results of a systematic review of exercise systematic reviews. An international panel of experts was identified by exercise systematic review authorship, established international profile in exercise research and practice and by peer referral. In round 1, the international panel of experts will be asked to rate the importance of each draft item and provide additional suggestions for revisions or new items. Consensus will be considered reached if at least 70% of the panel strongly agree/disagree that an item should be included or excluded. Where agreement is not reached or there are suggestions for altered or new items, these will be taken to round 2 together with an aggregated summary of round 1 responses. Following the second round, a ranking of item importance will be made to rationalise the number of items. The final template will be distributed to panel members for approval. Ethics and dissemination Ethics approval was received from The Cabrini Institute Ethics Committee, Melbourne, Australia (HREC 02-07-04-14). We plan to use a stepwise process to develop and refine a standardised and internationally agreed template for explicit reporting of exercise programmes. The template will be generalisable across all types of exercise interventions. The findings will be disseminated through peer-reviewed publications and conference presentations

Pre-Exposure Prophylaxis and the Promise of Combination Prevention Approaches

Pre-exposure prophylaxis (PrEP) for HIV prevention is a promising experimental approach currently being tested globally. A number of PrEP trials are evaluating the safety and effectiveness of PrEP in men who have sex with men (MSM) and other populations at risk for HIV, and results will be available from this first generation of efficacy trials over the next few years. Here we review the rationale for orally-administered antiretrovirals for prevention, and outline issues the first generation trials will address as well as questions that may be addressed in future studies. We also describe the rationale for combination prevention approaches that may combine PrEP with other prevention modalities as part of a larger prevention package

Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors.

IntroductionDeveloping guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings.MethodsWe use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies.ResultsA policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%).ConclusionsThese findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings

Can Male Circumcision Have an Impact on the HIV Epidemic in Men Who Have Sex with Men?

Background: Three trials have demonstrated the prophylactic effect of male circumcision (MC) for HIV acquisition among heterosexuals, and MC interventions are underway throughout sub-Saharan Africa. Similar efforts for men who have sex with men (MSM) are stymied by the potential for circumcised MSM to acquire HIV easily through receptive sex and transmit easily through insertive sex. Existing work suggests that MC for MSM should reach its maximum potential in settings where sexual role segregation is historically high and relatively stable across the lifecourse; HIV incidence among MSM is high; reported willingness for prophylactic circumcision is high; and pre-existing circumcision rates are low. We aim to identify the likely public health impact that MC interventions among MSM would have in one setting that fulfills these conditions—Peru—as a theoretical upper bound for their effectiveness among MSM generally. Methods and Findings: We use a dynamic, stochastic sexual network model based in exponential-family random graph modeling and parameterized from multiple behavioral surveys of Peruvian MSM. We consider three enrollment criteria (insertive during 100%, >80% or >60% of UAI) and two levels of uptake (25% and 50% of eligible men); we explore sexual role proportions from two studies and different frequencies of switching among role categories. Each scenario is simulated 10 times. We estimate that efficiency could reach one case averted per 6 circumcisions. However, the population-level impact of an optimistic MSM-MC intervention in this setting would likely be at most ∼5–10% incidence and prevalence reductions over 25 years. Conclusions: Roll-out of MC for MSM in Peru would not result in a substantial reduction in new HIV infections, despite characteristics in this population that could maximize such effects. Additional studies are needed to confirm these results for other MSM populations, and providers may consider the individual health benefits of offering MC to their MSM patients

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

What Drives the US and Peruvian HIV Epidemics in Men Who Have Sex with Men (MSM)?

In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru

Infrequent HIV Testing and Late HIV Diagnosis Are Common Among a Cohort of Black Men Who Have Sex With Men in 6 US Cities

Objective: US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM). Methods: HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count <200 cells per cubic millimeter or <350 cells per cubic millimeter at diagnosis. Results: HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no previous HIV diagnosis; 272 (21.2%) reported no HIV test in previous 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the previous 6 months (relative risk [RR]: 1.08, 95% confidence interval [CI]: 1.03 to 1.13), being unemployed (RR: 1.04, CI: 1.01 to 1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0 to 1.05). New HIV diagnoses were more likely among infrequent testers compared with men tested in the previous year (18.4% vs. 4.4%; odds ratio: 4.8, 95% CI: 3.2 to 7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells per cubic millimeter including 17 (20.2%) with CD4 <200 cells per cubic millimeter. Conclusions: Infrequent HIV testing, undiagnosed infection, and late diagnosis were common among BMSM in this study. New HIV diagnoses were more common among infrequent testers, underscoring the need for additional HIV testing and prevention efforts among US BMSM. Infrequent HIV Testing and Late HIV Diagnosis Are Common Among a Cohort of Black Men Who Have Sex With Men in 6 US Cities. Available from: https://www.researchgate.net/publication/265419180_Infrequent_HIV_Testing_and_Late_HIV_Diagnosis_Are_Common_Among_a_Cohort_of_Black_Men_Who_Have_Sex_With_Men_in_6_US_Cities [accessed Feb 4, 2016]

KIR/HLA Pleiotropism: Protection against Both HIV and Opportunistic Infections

The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS

Serosorting Is Associated with a Decreased Risk of HIV Seroconversion in the EXPLORE Study Cohort

Background: Seroadaptation strategies such as serosorting and seropositioning originated within communities of men who have sex with men (MSM), but there are limited data about their effectiveness in preventing HIV transmission when utilized by HIV-negative men. Methodology/Principal Findings: Data from the EXPLORE cohort of HIV-negative MSM who reported both seroconcordant and serodiscordant partners were used to evaluate serosorting and seropositioning. The association of serosorting and seropositioning with HIV seroconversion was evaluated in this cohort of high risk MSM from six U.S. cities. Serosorting was independently associated with a small decrease in risk of HIV seroconversion (OR = 0.88; 95%CI, 0.81–0.95), even among participants reporting $10 partners. Those who more consistently practiced serosorting were more likely to be white (p = 0.01), have completed college (p =,0.0002) and to have had 10 or more partners in the six months before the baseline visit (p = 0.01) but did not differ in age, reporting HIV-infected partners, or drug use. There was no evidence of a seroconversion effect with seropositioning (OR 1.02, 95%CI, 0.92–1.14). Significance: In high risk HIV uninfected MSM who report unprotected anal intercourse with both seroconcordant and serodiscordant partners, serosorting was associated with a modest decreased risk of HIV infection. To maximize any potential benefit, it will be important to increase accurate knowledge of HIV status, through increased testing frequency

Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS

Background From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLAB* 35 subtypes with different peptide-binding specificities. Results HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLAB* 3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLAB* 35-Px alleles, some of which differ from HLA-B*35- PY alleles by only one amino acid residue. Conclusions This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1