HIV Preexposure Prophylaxis: A Review Riddell, James; Amico, K. Rivet; Mayer, Kenneth H
JAMA : the journal of the American Medical Association,
03/2018, Letnik:
319, Številka:
12
Journal Article
Recenzirano
IMPORTANCE: About 40 000 Americans and 2 million people worldwide are newly infected with HIV each year. The combination antiretroviral regimen, tenofovir disoproxil fumarate (TDF)/emtricitabine, ...taken as a single pill once daily, has been shown to prevent HIV transmission but is used by fewer than 20% of people who could benefit in the United States. OBSERVATIONS: PubMed was searched on February 15, 2018, using the search terms pre-exposure, prophylaxis, HIV, and PrEP to identify English-language articles published between 2010 and 2018. Four placebo-controlled randomized clinical trials have demonstrated that preexposure prophylaxis (PrEP) with daily dosing of TDF/emtricitabine significantly reduces HIV acquisition in men who have sex with men, high-risk heterosexuals, and injection drug users who share injection equipment. The efficacy of daily TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence. TDF/emtricitabine is safe and well-tolerated. Only 2% of people discontinue PrEP because of adverse effects. Sexually transmitted infections are common among those using PrEP. Resistance to TDF/emtricitabine when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection who have false-negative findings on HIV antibody/antigen testing due to HIV infection acquired within 7 to 10 days of testing. Effective methods are needed to identify individuals at high risk for acquiring HIV, ensure their access to PrEP, and maximize medication adherence. CONCLUSIONS AND RELEVANCE: TDF/emtricitabine is an effective and safe therapy for preventing HIV transmission. Increasing prescription of TDF/emtricitabine for patients at risk of acquiring HIV has the potential to reduce new HIV infections.
A study conducted in Tanzania aimed to improve the linkage to HIV care for hospitalized patients. The study compared the effectiveness of the Daraja intervention, which involved sessions conducted by ...social workers, with enhanced standard care. The primary outcome measured was 12-month all-cause mortality, with secondary outcomes including HIV clinic attendance, ART use, and viral load suppression. The intervention did not reduce mortality but did improve time to HIV clinic linkage, ART initiation, clinic retention, ART adherence, and viral load suppression. The study highlights the importance of selecting appropriate primary and secondary outcomes in clinical trials, focusing on the specific targets of the intervention. The Daraja intervention offers a cost-effective approach to improving engagement in clinical care and viral load suppression. The study also emphasizes the need for scalable interventions that address the complexities of HIV care and support overall well-being.
Despite considerable discussion and debate about adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV), scant data are available that characterize patterns of adherence ...to open-label PrEP. The current evidence base is instead dominated by research on adherence to placebo-controlled investigational drug by way of drug detection in active-arm participants of large randomized controlled trials (RCTs). Important differences between the context of blinded RCTs and open-label use suggest caution when generalizing from study product adherence to real-world PrEP use. Evidence specific to open-label PrEP adherence is presently sparse but will expand rapidly over the next few years as roll-out, demonstration projects, and more rigorous research collect and present findings. The current evidence bases established cannot yet predict uptake, adherence, or persistence with open-label effective PrEP. Emerging evidence suggests that some cohorts could execute better adherence in open-label use vs placebo-controlled research. Uptake of PrEP is presently slow in the United States; whether this changes as grassroots and community efforts increase awareness of PrEP as an effective HIV prevention option remains to be determined. As recommended by multiple guidelines for PrEP use, all current demonstration projects offer PrEP education and/or counseling. PrEP support approaches generally fall into community-based, technology, monitoring, and integrated sexual health promotion approaches. Developing and implementing research that moves beyond simple correlates of either study product use or open-label PrEP adherence toward more comprehensive models of sociobehavioral and socioecological adherence determinants would greatly accelerate progress. Intervention research is needed to identify effective models of support for open-label PrEP adherence.
Summary Background The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. We aimed to assess these factors in a cohort of HIV-negative people at risk of ...infection. Methods In our cohort study, men and transgender women who have sex with men previously enrolled in PrEP trials (ATN 082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension. We measured drug concentrations in plasma and dried blood spots in seroconverters and a random sample of seronegative participants. We assessed PrEP uptake, adherence, sexual practices, and HIV incidence. Statistical methods included Poisson models, comparison of proportions, and generalised estimating equations. Findings We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP. Uptake was higher among those reporting condomless receptive anal intercourse (416/519 81% vs 809/1084 75%, p=0·003) and having serological evidence of herpes (612/791 77% vs 613/812 75% p=0·03). Of those receiving PrEP, HIV incidence was 1·8 infections per 100 person-years, compared with 2·6 infections per 100 person-years in those who concurrently did not choose PrEP (HR 0·51, 95% CI 0·26–1·01, adjusted for sexual behaviours), and 3·9 infections per 100 person-years in the placebo group of the previous randomised phase (HR 0·49, 95% CI 0·31–0·77). Among those receiving PrEP, HIV incidence was 4·7 infections per 100 person-years if drug was not detected in dried blood spots, 2·3 infections per 100 person-years if drug concentrations suggested use of fewer than two tablets per week, 0·6 per 100 person-years for use of two to three tablets per week, and 0·0 per 100 person-years for use of four or more tablets per week (p<0·0001). PrEP drug concentrations were higher among people of older age, with more schooling, who reported non-condom receptive anal intercourse, who had more sexual partners, and who had a history of syphilis or herpes. Interpretation PrEP uptake was high when made available free of charge by experienced providers. The effect of PrEP is increased by greater uptake and adherence during periods of higher risk. Drug concentrations in dried blood spots are strongly correlated with protective benefit. Funding US National Institutes of Health.
After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). Adherence to ART is among the key ...determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV.
A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation.
Recommendations are provided for monitoring entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.
Medication adherence is an important but highly complex set of behaviors, which for life-threatening and infectious diseases such as HIV carry critical consequences for individual and public health. ...There is growing evidence that mobile phone text messaging interventions (mHealth) connecting providers with patients positively impact medication adherence, particularly two-way engagement platforms that require bidirectional communication versus one-way in which responses are not mandatory. However, mechanisms of action have not been well defined. The Behavior Change Wheel is a comprehensive framework for behavior change that includes an all-encompassing model of behavior known as Capability Opportunity Motivation-Behavior and is complemented by a taxonomy of behavior change techniques. Evaluating mHealth interventions for medication adherence using these tools could provide useful insights that may contribute to optimizing their integration into the healthcare system and successful scaling-up.
This study aimed to help address the current knowledge gap regarding how two-way mHealth interventions for medication adherence may work by applying the Behavior Change Wheel to characterize WelTel: an interactive digital health outreach platform with robust evidence for improving adherence to antiretroviral therapy.
To characterize how WelTel may promote medication adherence, we applied the Behavior Change Wheel to systematically (1) generate a behavioral diagnosis through mapping known antiretroviral therapy adherence barriers onto the Capability Opportunity Motivation-Behavior model of behavior, (2) specify the behavior change techniques that WelTel delivers, (3) link identified behavior change techniques to corresponding intervention functions of the Behavior Change Wheel, and (4) connect these behavior change techniques and intervention functions to respective Capability Opportunity Motivation-Behavior influences on behavior to determine potential mechanisms of action.
Our evaluation of WelTel using the Behavior Change Wheel suggests that most of its impact is delivered primarily through its personalized communication component, in which 8 different behavior change techniques were identified and linked with 5 intervention functions (environmental restructuring, enablement, education, persuasion, and training). Its mechanisms of action in promoting antiretroviral therapy adherence may involve addressing all Capability Opportunity Motivation-Behavior influences on behavior (physical and psychological capability, physical and social opportunity, reflective and automatic motivation).
Systematically unpacking the potential active ingredients of effective interventions facilitates the creation and implementation of more parsimonious, tailored, and targeted approaches. Evaluating WelTel using the Behavior Change Wheel has provided valuable insights into how and why such interactive two-way mHealth interventions may produce greater impact than one-way in addressing both nonintentional and intentional forms of nonadherence. The application of the Behavior Change Wheel for evidence synthesis across mHealth interventions targeting various conditions would contribute to strengthening the knowledge base regarding how they may work to impact medication adherence behavior.
INTRODUCTION:Youth living with HIV are highly under-represented in the evidence base for adherence interventions, despite their diverse and unique needs and barriers.
OBJECTIVE:This systematic review ...aimed to identify antiretroviral therapy (ART) adherence interventions specifically targeting adolescents and young adults (defined as ages 13–24) with the goal of characterizing the evidence base.
METHODS:Articles were identified using the PubMed database and cover work published through September 14, 2015. Inclusion criteria(1) average age 13 to 24, (2) HIV positive, (3) on or beginning ART, (4) intervention targeted ART adherence in full or in part, (5) reported adherence, viral load, and/or CD4 count outcomes. Strength of evidence was defined as level 1 randomized controlled trial (RCT) with significance testing on outcomes, 2 (within group studies with statistical testing on outcomes), 3 (RCTs with descriptive results), or 4 (within group studies with descriptive results).
RESULTS:Of 151 articles, 10 met inclusion criteria. Published between 2003 and 2014, these studies evaluated diverse intervention approaches. Most were conducted in the US and were small pilots that have yet to be replicated despite promising results. Only 3 studies met criteria for highest level strength of evidence; 2 supported a phone-based counseling approach with adherence monitors and 1 for weekly individual and family counseling.
CONCLUSIONS:Despite nearly 20 years passing since the wide-scale availability of ART, and clear recognition that adolescents and youth adults fair worse on the cascade of HIV care, the evidence base remains sparse and underdeveloped. Promising approaches need replication and more rigorous studies are desperately needed.
IMPORTANCE: Several randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about ...adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM). OBJECTIVE: To assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States. DESIGN, SETTING, AND PARTICIPANTS: Demonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015. INTERVENTIONS: A combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring. MAIN OUTCOMES AND MEASURES: Concentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition. RESULTS: Overall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P < .001) were less likely to have protective levels, whereas those with stable housing (86.8%; P = .02) and those reporting at least 2 condomless anal sex partners in the past 3 months (88.6%; P = .01) were more likely to have protective levels. The mean number of anal sex partners declined during follow-up from 10.9 to 9.3, whereas the proportion engaging in condomless receptive anal sex remained stable at 65.5% to 65.6%. Overall STI incidence was high (90 per 100 person-years) but did not increase over time. Two individuals became HIV infected during follow-up (HIV incidence, 0.43 95% CI, 0.05-1.54 infections per 100 person-years); both had tenofovir diphosphate levels consistent with fewer than 2 doses/wk at seroconversion. CONCLUSIONS AND RELEVANCE: The incidence of HIV acquisition was extremely low despite a high incidence of STIs in a large US PrEP demonstration project. Adherence was higher among those participants who reported more risk behaviors. Interventions that address racial and geographic disparities and housing instability may increase the impact of PrEP.
Antiretroviral therapy (ART) adherence is suboptimal among gay, bisexual, and other men who have sex with men (GBMSM). Online interventions that incorporate social support represent new opportunities ...to improve adherence. This study focused on how social support was provided and sought within a technology-based ART adherence intervention. We coded and analyzed 1,751 messages. Within the social support messages, half of the time participants sought social support and half of the time they provided social support. Emotional and informational support were the most frequently exchanged forms. The most frequent topic that participants sought support around was interpersonal relationships (29%), followed by HIV care and treatment (28%). Similarly, 31% and 27% of messages in which participants provided support was related to HIV treatment and care and interpersonal relationships, respectively. HIV treatment and care issues most salient were ART adherence, lab results and upcoming tests, ART side effects, changes in ART regimens, and relationships with healthcare providers. Participants used the messaging feature in this intervention to spontaneously discuss and exchange support around HIV treatment and care. This analysis provided an opportunity to understand how participants informally interact with one another, how they seek and provide social support online, and their salient personal issues.
The National HIV/AIDS Strategy and the promise of treatment as prevention have garnered considerable attention from the policy, practice, and scientific communities, with the treatment cascade ...becoming the sentinel image illustrating the domestic human immunodeficiency virus (HIV) epidemic. The cascade depicts prevalence estimates for sequential steps from HIV diagnosis through viral suppression, the most striking of which is that >50% of persons diagnosed with HIV are not in medical care. This heterogeneous group includes individuals not linked to medical care following HIV diagnosis and those entering care who are not retained, requiring reengagement from a range of community settings. This review synthesizes the state of engagement in HIV care in the United States, focusing on research, practice, and policy considerations. Included are conceptual frameworks, a review of health implications, measurement, monitoring, and evidence-based intervention approaches, and a look to the future in addressing the greatest challenge and opportunity facing our domestic HIV epidemic.
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