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BackgroundPopulation‐based and longitudinal information regarding sexual risk behavior among patients with multidrug resistant (MDR) HIV and their sexual partners is of great public health and clinical importance.ObjectiveTo characterize the HIV sexual risk behaviors of patients with and without drug‐resistant HIV in the clinical care setting over time.Measurements393 HIV‐positive patients completed questionnaires of self‐reported sexual risk behaviors at approximate 6‐month intervals extending over 24 months. HIV viral load and genotypic drug resistance obtained during the same time points were matched to the behavioral data. Multidrug resistance was defined as having resistance to 2 or 3 antiretroviral (ARV) drug classes.ResultsIn serial cross‐sectional analyses, 393 patients (44% female and 79% heterosexual) contributed 919 matched behavioral and virologic results over the 24 months of data collection. Of these, 250 patients (64%) reported having sex during at least 1 survey period resulting in greater than 10,000 sexual events with more than 1000 partners. Unprotected sexual behavior was reported by 45% of sexually active patients, resulting in 34% of all sex events that exposed 29% of all partners. Of these patients with unprotected sexual events, 31% had HIV drug resistance 11.6% with resistance to 2 classes of ARVs (2‐class), and 1.8% with 3‐class ARV resistance at the time of a sexual risk event. Close to 1000 or 28% of all unprotected sexual events involved resistant strains (11% of these with resistance to 2 classes and 0.2% with 3‐class resistance, exposing 20% of unprotected sexual partners to resistant HIV (8% to 2‐class and 0.6% to 3‐class resistance).In longitudinal analysis among the 78 patients who reported a cumulative total of 12 months of sexual history and had resistance testing, 38% reported engaging in unprotected sexual behavior. There was substantial and complex variation in the distribution of unprotected sexual events and in the detection of resistance over time.ConclusionIn this study of HIV sexual risk and resistance over time among HIV‐infected patients in clinical care, a substantial proportion engaged in unprotected sex and had drug‐resistant HIV, frequently exposing partners to 1‐ or 2‐class resistant HIV strains. However, relatively few exposures involved 3‐class resistance. The dynamics of sexual risk behavior and HIV drug resistance are complex and vary over time and urgently require both general and targeted interventions to reduce transmission of resistant HIV.

After two decades of microbicide clinical trials it remains uncertain if vaginally‐ delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre‐licensure implementation trials, Phase IV post‐marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large‐scale microbicide efficacy trials completed to‐date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post‐marketing research, and microbicide introduction and delivery programs.

AbstractIntroductionStimulant and heavy alcohol use are prevalent and associated with elevated risk for HIV seroconversion among men who have sex with men (MSM) and transgender women. In addition, each can pose difficulties for antiretroviral adherence among people living with HIV. Scant research has examined the associations of stimulant and heavy alcohol use with adherence to daily oral pre‐exposure prophylaxis (PrEP) among MSM and transgender women. To address this gap in the literature, we evaluated the hypothesis that stimulant use and binge drinking are prospectively associated with sub‐optimal PrEP adherence.MethodsWe analysed data from participants in a nested case‐cohort in the iPrEx open label extension. Stimulant use (i.e. powder cocaine, crack‐cocaine, cocaine paste, methamphetamine, cathinone) and binge drinking (i.e. ≥5 drinks in a single day) in the last 30 days were assessed. Baseline urine was tested for stimulants using immunoassays to reduce misclassification. Sub‐optimal adherence was defined as tenofovir drug concentrations in dried blood spots less than 700 fmol per punch, indicative of less than four doses per week. We tested the prospective association of stimulant use and binge drinking with sub‐optimal adherence at the 4‐week follow‐up visit.Results and DiscussionData from 330 participants were analysed. The majority of the participants were MSM (89%) with a median age at baseline of 29 years (interquartile range 24 to 39). Approximately 16% (52/330) used stimulants and 22% (72/330) reported binge drinking in the last 30 days. Stimulant users had fivefold greater odds of sub‐optimal PrEP adherence compared to non‐users in adjusted analysis (adjusted odds ratio [aOR] 5.04; [95% CI 1.35 to 18.78]). Self‐reported binge drinking was not significantly associated with sub‐optimal adherence after adjusting for stimulant use and baseline confounders (aOR 1.16 [0.49 to 2.73]). Depressive symptoms, being transgender, and number of sex partners were also not significantly associated with sub‐optimal PrEP adherence (p > 0.05).ConclusionsStimulant use is a risk factor for sub‐optimal PrEP adherence in the month following PrEP initiation. Comprehensive prevention approaches that reduce stimulant use may optimize PrEP adherence. Creating adherence plans that specifically address PrEP dosing in the context of ongoing stimulant use should also be considered.

IntroductionProduct adherence and its measurement have emerged as a critical challenge in the evaluation of new HIV prevention technologies. Long‐acting ARV‐based vaginal rings may simplify use instructions and require less user behaviour, thereby facilitating adherence. One ARV‐based ring is in efficacy trials and others, including multipurpose rings, are in the pipeline. Participant motivations, counselling support and measurement challenges during ring trials must still be addressed. In previous HIV prevention trials, this has been done largely using descriptive and post‐hoc methods that are highly variable and minimally evaluated. We outline an interdisciplinary framework for systematically investigating promising strategies to support product uptake and adherence, and to measure adherence in the context of randomized, blinded clinical trials.DiscussionThe interdisciplinary framework highlights the dual use of adherence measurement (i.e. to provide feedback during trial implementation and to inform interpretation of trial findings) and underscores the complex pathways that connect measurement, adherence support and enacted adherence behaviour. Three inter‐related approaches are highlighted: 1) adherence support – sequential efforts to define motivators of study product adherence and to develop, test, refine and evaluate adherence support messages; 2) self‐reported psychometric measures – creation of valid and generalizable measures based in easily administered scales that capture vaginal ring use with improved predictive ability at screening, baseline and follow‐up that better engage participants in reporting adherence; and 3) more objective measurement of adherence – real‐time adherence monitoring and cumulative measurement to correlate adherence with overall product effectiveness through innovative designs, models and prototypes using electronic and biometric technologies to detect ring insertion and/or removal or expulsion. Coordinating research along these three pathways will result in a comprehensive approach to product adherence within clinical trials.ConclusionsBetter measurement of adherence will not, by itself, ensure that future effectiveness trials will be able to address the most basic question: if the product is used per instructions, will it prevent HIV transmission? The challenges to adherence measurement must be addressed as one component of a more integrated system that has as its central focus adherence as a behaviour emerging from the social context of the user.

AbstractIntroductionCOVID‐19 parallels HIV in many ways. Socio‐behavioural science has been critical in elucidating the context and factors surrounding individual levels of engagement with known effective prevention and treatment tools for HIV, thus offering important lessons for ongoing efforts to combat the COVID‐19 pandemic.DiscussionNon‐adherence to effective disease mitigation strategies (e.g. condoms for HIV and masks for COVID‐19) can be attributed in part to prioritizing comfort, convenience and individual autonomy over public health. Importantly, misinformation can fuel denialism and conspiracies that discredit scientific knowledge and motivate nonadherence. These preferences and the extent to which individuals can act on their preferences may be constrained by the structures and culture in which they live. Both HIV and COVID‐19 have been politicized and influenced by evolving recommendations from scientists, clinicians, policymakers and politically motivated organizations. While vaccines are vital for ending both pandemics, their impact will depend on availability and uptake. Four decades of experience with the HIV epidemic have shown that information alone is insufficient to overcome these challenges; interventions must address the underlying, often complex factors that influence human behaviour. This article builds from socio‐behavioural science theory and describes practical and successful approaches to enable and support adherence to prevention and treatment strategies, including vaccine adoption. Key methods include reframing tools to enhance motivation, promoting centralized sources of trusted information, strategic development and messaging with and within key populations (e.g. through social media) and appealing to self‐empowerment, altruism and informed decision making. Orchestrated evidence‐based activism is needed to overcome manipulative politicization, while consistent transparent messaging around scientific discoveries and clinical recommendations are critical for public acceptance and support. Ultimately, the effectiveness of COVID‐19 vaccines will depend on our ability to engender trust in the communities most affected.ConclusionsMany lessons learned from socio‐behavioural science in the HIV pandemic are applicable to the COVID‐19 pandemic. Individual behaviour must be understood within its interpersonal and societal context to address the current barriers to adherence to disease‐mitigating strategies and promote an effective response to the COVID‐19 pandemic, which is likely to be endured for the foreseeable future.

IntroductionCOVID-19 parallels HIV in many ways. Socio-behavioural science has been critical in elucidating the context and factors surrounding individual levels of engagement with known effective prevention and treatment tools for HIV, thus offering important lessons for ongoing efforts to combat the COVID-19 pandemic.DiscussionNon-adherence to effective disease mitigation strategies (e.g. condoms for HIV and masks for COVID-19) can be attributed in part to prioritizing comfort, convenience and individual autonomy over public health. Importantly, misinformation can fuel denialism and conspiracies that discredit scientific knowledge and motivate nonadherence. These preferences and the extent to which individuals can act on their preferences may be constrained by the structures and culture in which they live. Both HIV and COVID-19 have been politicized and influenced by evolving recommendations from scientists, clinicians, policymakers and politically motivated organizations. While vaccines are vital for ending both pandemics, their impact will depend on availability and uptake. Four decades of experience with the HIV epidemic have shown that information alone is insufficient to overcome these challenges; interventions must address the underlying, often complex factors that influence human behaviour. This article builds from socio-behavioural science theory and describes practical and successful approaches to enable and support adherence to prevention and treatment strategies, including vaccine adoption. Key methods include reframing tools to enhance motivation, promoting centralized sources of trusted information, strategic development and messaging with and within key populations (e.g. through social media) and appealing to self-empowerment, altruism and informed decision making. Orchestrated evidence-based activism is needed to overcome manipulative politicization, while consistent transparent messaging around scientific discoveries and clinical recommendations are critical for public acceptance and support. Ultimately, the effectiveness of COVID-19 vaccines will depend on our ability to engender trust in the communities most affected.ConclusionsMany lessons learned from socio-behavioural science in the HIV pandemic are applicable to the COVID-19 pandemic. Individual behaviour must be understood within its interpersonal and societal context to address the current barriers to adherence to disease-mitigating strategies and promote an effective response to the COVID-19 pandemic, which is likely to be endured for the foreseeable future.

AbstractIntroductionLimited data exist on acceptability of candidate pre‐exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the US‐based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study.MethodsWomen participated in the study between March 2013 and November 2015. We analysed computer‐assisted self‐interview (CASI) surveys among 130 women and conducted in‐depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/late‐2015.ResultsMost women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged over‐reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included "simply forgetting" and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partners') low‐risk behaviour and concerns about affordability – but not because of side effects or other characteristics of the regimens.ConclusionsImproving HIV prevention options for US women will require access to affordable PrEP as well as expanding women's understanding of relationship‐ and community‐level factors that increase their risk of acquiring HIV.

AbstractIntroduction: Successful population‐level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale‐up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource‐limited settings.Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource‐limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta‐analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low‐ and middle‐income countries. Interventions are categorized broadly as education and counselling; information and communication technology‐enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described.Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource‐limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi‐media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement.Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS.