A decade after widespread recognition that adherence to medication regimens is key to antiretroviral (ARV) effectiveness, considerable controversy remains regarding a “gold standard” for adherence measurement. Each adherence measurement approach has strengths and weaknesses and each rests on specific assumptions. The range of assumptions regarding adherence measurement and the diversity with which each approach is implemented strongly suggest that the evaluation of a particular measure outside of the context in which it was used (e.g. the study’s operational protocol) may result in undeserved confidence or lack of confidence in study results. The purpose of this paper is to propose a set of best practices across commonly used measurement methods. Recommendations regarding what information should be included in published reports regarding how adherence was measured are provided to promote improvement in the quality of measurement of medication adherence in research.
Adherence measurement; Adherence self-report; Electronic monitoring devices; Pill-count; Pharmacy refill
Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior.
Design and methods
Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy.
Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12).
There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.
In the past 25 years, a tremendous amount of time and resources have been committed to developing evidence-based HIV prevention interventions. More recently, there have been noteworthy efforts to develop an infrastructure and related policies to promote the dissemination (i.e., “the targeted distribution of information and intervention materials to a specific public health or clinical practice audience”) of evidence-based interventions. Despite these advances, however, we have had comparatively little success in the effective implementation (i.e., “the use of strategies to adopt and integrate evidence-based health interventions and change practice patterns within specific settings”) of such interventions in everyday practice or community settings. The objective of the current paper is to highlight select and initial areas of research that are critically needed to advance the state-of-the-science of implementation of HIV prevention interventions in our broader efforts to curb the epidemic worldwide.
Implementation; HIV/AIDS; Prevention; Intervention; Dissemination
Aims of this study were to assess the associations between stimulant use and attitudes toward and engagement in HIV medical care and to examine technology use among stimulant-using and nonstimulant-using men who have sex with men (MSM). HIV-positive MSM (n = 276; mean age = 42 years; 71% white, non-Hispanic; 43% with college degree) completed an online survey in 2009. Most men (69%) had not missed any scheduled HIV medical appointments in the past year, while 23% had missed at least one, and 9% had not attended any appointments. Stimulant use was significantly associated with not attending any HIV medical appointments in the unadjusted model (relative risk ratio (RRR) = 2.84, 95% CI [1.07, 7.58]), as well as in models adjusted for demographic (RRR = 3.16, 95% CI [1.13, 8.84]) and psychosocial (RRR = 3.44, 95% CI [1.17, 10.15]) factors (Ps < 0.05). Fewer stimulant-using than non-stimulant-using men rated HIV medical care a high priority (57% versus 85%; P < 0.01). Few significant differences were found in online social networking or mobile phone use between stimulant-using and non-stimulant-using MSM, even when stratified by engagement in HIV care. Findings indicate that stimulant use is uniquely associated with nonengagement in HIV medical care in this sample, and that it may be possible to reach stimulant-using MSM using online social networking and mobile technologies.
The current study provides a qualitative test of a recently proposed application of an Information, Motivation, Behavioral Skills (IMB) model of health behavior situated to the social-environmental, structural, cognitive-affective, and behavioral demands of retention in HIV care. Mixed-methods qualitative analysis was used to identify the content and context of critical theory-based determinants of retention in HIV care, and to evaluate the relative fit of the model to the qualitative data collected via in-depth semi-structured interviews with a sample of inner-city patients accessing traditional and nontraditional HIV care services in the Bronx, NY. The sample reflected a diverse marginalized patient population who commonly experienced comorbid chronic conditions (e.g., psychiatric disorders, substance abuse disorders, diabetes, hepatitis C). Through deductive content coding, situated IMB model-based content was identified in all but 7.1% of statements discussing facilitators or barriers to retention in HIV care. Inductive emergent theme identification yielded a number of important themes influencing retention in HIV care (e.g., acceptance of diagnosis, stigma, HIV cognitive/physical impairments, and global constructs of self-care). Multiple elements of these themes strongly aligned with the model's IMB constructs. The convergence of the results from both sets of analysis demonstrate that participants' experiences map well onto the content and structure of the situated IMB model, providing a systematic classification of important theoretical and contextual determinants of retention in care. Future intervention efforts to enhance retention in HIV care should address these multiple determinants (i.e., information, motivation, behavioral skills) of self-directed retention in HIV care.
It is unknown if online social networking technologies are already highly integrated among some people living with HIV (PLWH) or have yet to be adopted. To fill this gap in understanding, 312 PLWH (84% male, 69% white) residing in the US completed on online survey in 2009 of their patterns of social networking and mobile phone use. Twenty-two persons also participated in one of two online focus groups. Results showed that 76% of participants with lower adherence to HIV medication used social networking websites/features at least once a week. Their ideal online social networking health websites included one that facilitated socializing with others (45% of participants) and relevant informational content (22%), although privacy was a barrier to use (26%). Texting (81%), and to a lesser extent mobile web-access (51%), was widely used among participants. Results support the potential reach of online social networking and text messaging intervention approaches.
Online social network; mobile phone; online survey; online focus group; people living with 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.
vaginal microbicides; HIV prevention; clinical trial adherence
The success of potent combination antiretroviral therapy (ART) for HIV infection is compromised primarily by failure to maintain optimal levels of adherence over the long term. Recent reviews suggest behavioral interventions to promote ART adherence can have significant effects, but these tend to be small and to diminish over time; sustained improvements in biomarkers are particularly elusive. In this article, we update current reviews, focusing specifically on the 13 studies evaluating behavioral interventions to promote ART adherence published since September 2007. We describe the range of intervention strategies employed and qualitatively summarize findings of their efficacy. In conclusion, we consider implications and offer strategies for enhancing adherence in clinic-based HIV care prior to ART initiation, at initiation, and over the course of treatment.
HIV/AIDS; ART; Adherence; Interventions; Review
Adherence is a critical component of the success of antiretroviral-based pre-exposure prophylaxis (PrEP) in averting new HIV-infections. Ensuring drug availability at the time of potential HIV exposure relies on self-directed product use. A deeper understanding of how to best support sustained PrEP adherence remains critical to current and future PrEP efforts. This paper provides a succinct synthesis of the adherence support experiences from four pivotal PrEP trials—Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, FEM-PrEP, Iniciativa Prophylaxis (iPrEx), and Vaginal and Oral Interventions to Control the Epidemic (VOICE). Notwithstanding variability in the design, population/cohort, formulation, drug, dosing strategy, and operationalization of adherence approaches utilized in each trial, the theoretical basis and experiences in implementation and monitoring of the approaches used by these trials provide key lessons for optimizing adherence in future research and programmatic scale-up of PrEP. Recommendations from across these trials include participant-centered approaches, separating measurement of adherence from adherence counseling, incorporating tailored strategies that go beyond education, fostering motivation, and addressing the specific context in which an individual incorporates and negotiates PrEP use.
PrEP; Microbicides; Adherence; Intervention; Counseling; Clinical trials; HIV prevention
Diabetes education for ethnic minorities should address variations in values underlying motivations, preferences, and behaviors of individuals within an ethnic group. This paper describes the development and implementation of a culturally tailored diabetes intervention for Puerto Rican Americans that can be delivered by a health care paraprofessional and implemented in routine clinical care. We describe a formative process, including interviews with providers, focus groups with patients and a series of multidisciplinary collaborative workshops used to inform intervention content. We highlight the intervention components and link them to a well-validated health behavior change model. Finally, we present support for the intervention’s clinical effects, feasibility, and acceptability and conclude with implications and recommendations for practice. Lessons learned from this process should guide future educational efforts in routine clinical care.
Culturally tailored; diabetes; behavior change; primary care; Puerto Rican
Following HIV diagnosis and linkage to care, achieving and sustaining viral load (VL) suppression has implications for patient outcomes and secondary HIV prevention. We evaluated factors associated with expeditious VL suppression and cumulative VL burden among patients establishing outpatient HIV care.
Patients initiating HIV medical care from January 2007-October 2010 at the University of Alabama at Birmingham and University of Washington were included. Multivariable Cox proportional hazards and linear regression models were used to evaluate factors associated with time to VL suppression (<50 copies/mL) and cumulative VL burden, respectively. Viremia copy-years (VCY), a novel area under the longitudinal VL curve measure, was used to estimate 2-year cumulative VL burden from clinic enrollment.
Among 676 patients, 63% achieved VL<50 copies/mL in a median 308 days. In multivariable analysis, patients with more time-updated “no show” visits experienced delayed VL suppression (HR=0.83 per “no show” visit, 95%CI=0.76,0.91). In multivariable linear regression, visit non-adherence was independently associated with greater cumulative VL burden (log10VCY) during the first two years in care (Beta coefficient=0.11 per 10% visit non-adherence, 95%CI=0.04-0.17). Across increasing visit adherence categories, lower cumulative VL burden was observed (mean ± standard deviation log10 copy × years/mL); 0-79% adherence: 4.6 ± 0.8; 80-99% adherence: 4.3 ± 0.7; and 100% adherence: 4.1 ± 0.8 log10 copy × years/mL, respectively (P<0.01).
Higher rates of early retention in HIV care are associated with achieving VL suppression and lower cumulative VL burden. These findings are germane for a test and treat approach to HIV prevention.
HIV; Viral load; Retention in care; Adherence; Engagement in care
Deep South; engagement in care; HIV infection; qualitative research
Delayed entry into HIV clinical care and poor retention in care has been associated with increased morbidity and mortality. To characterize the reasons for patients who eventually did enter HIV care after a delay and/or returned to care after a gap of 6 or more months, 130 semi-structured interviews about barriers to and facilitators for prompt entry into and sustained HIV clinical care were conducted in a clinic setting in the Deep South; responses were coded and analyzed quantitatively. Barriers/facilitators were positioned within superordinate categories of personal and structural barriers/facilitators and denial. Personal barriers to entry into care outweighed structural barriers, with denial reported by 74% of the sample. Barriers to retention in care were more evenly distributed between personal and structural barriers, with denial a barrier for 24%. Because of the high incidence of denial-based barriers, the role of this barrier and its resolution should be explored further.
barriers; Deep South; engagement in care; facilitators; HIV
Diabetes education for ethnic minorities should address variations in values underlying motivations, preferences, and behaviors of individuals within an ethnic group. This paper describes the development and implementation of a culturally tailored diabetes intervention for Puerto Ricans that can be delivered by a health care paraprofessional and implemented in routine clinical care. We describe a formative process, including interviews with providers, focus groups with patients and a series of multidisciplinary collaborative workshops used to inform intervention content. We highlight the intervention components and link them to a well-validated health behavior change model. Finally, we present support for the intervention’s clinical effects, feasibility, and acceptability and conclude with implications and recommendations for practice. Lessons learned from this process should guide future educational efforts in routine clinical care.
Culturally tailored; Diabetes; Behavior change; Primary care; Puerto Rican
Frameworks are needed to inform diabetes self-care programs for diverse populations. We tested the Information-Motivation-Behavioral Skills (IMB) model among Puerto Ricans with Type 2 diabetes (N=118). Structural equation models evaluated model fit and interrelations among constructs. For diet behavior, information and motivation related to behavioral skills (r=0.19, p<0.05 and r=0.39, p<0.01, respectively); behavioral skills related to behavior (r=0.42, p<0.01 and r=0.32, p<0.05); and behavior was related to glycemic control (r=−0.26, p<0.05). For exercise, personal motivation related to behavioral skills (r=0.53, p<0.001), and behavioral skills related to behavior (r=0.45, p<0.001). The IMB model could inform interventions targeting these behaviors in diabetes.
Information; motivation; behavioral skills (IMB) model; glycemic control; Puerto Rican; diabetes; behavior
The Information-Motivation-Behavioral Skills (IMB) model of health behavior change informed the design of a brief, culturally-tailored diabetes self-care intervention for Puerto Ricans with Type 2 diabetes. Participants (n = 118) were recruited from an outpatient, primary care clinic at an urban hospital in the northeast U.S. ANCOVA models evaluated intervention effects on food label reading, diet adherence, physical activity, and glycemic control (HbA1c). At follow-up, the intervention group was reading food labels and adhering to diet recommendations significantly more than the control group. While the mean HbA1c values decreased in both groups (Intervention: 0.48% vs. Control: 0.27% absolute decrease), only the intervention group showed a significant improvement from baseline to follow-up (p < .008) corroborating improvements in self-care behaviors. Findings support the use of the IMB model to culturally tailor diabetes interventions and to enhance patients’ knowledge, motivation, and behavior skills needed for self-care.
information motivation behavioral skills model; Puerto Rican; culture; tailored; diabetes self-care; behavior change
HIV prevalence in the American Deep South has reached crisis proportions and greater numbers of patients are enrolling in clinical care and beginning antiretroviral therapy (ART). In order to gain maximum benefit from ART, patients must sustain high levels of adherence to demanding regimens over extended periods of time. Many patients are unable to maintain high rates of adherence and may need assistance to do so, which may be based upon an understanding of barriers to adherence for a given population. The current study sought to gain understanding of barriers to adherence for a mixed urban/rural HIV-positive patient population in Mississippi and to determine whether barriers to adherence may be specific to gender, employment, depressive symptoms or educational attainment status. Seventy-two patients who missed a dose of ART medication over the last three days endorsed the top five reasons for missing a dose as: (1) not having the medication with them, (2) sleeping through the dose time, (3) running out of the medication, (4) being busy with other things and (5) other. Reported barriers were fairly consistent across different groups, although women and those classified as having moderate to severe depressive symptoms reported different patterns of adherence barriers. Results suggest that adherence interventions implemented in the Deep South must take into account specific barriers faced by individuals within this region, where stigma, gender disparities and limited resources are prevalent.
High levels of adherence to antiretroviral therapy (ART) are critical to the management of HIV, yet many people living with HIV do not achieve these levels. There is a substantial body of literature regarding correlates of adherence to ART, and theory-based multivariate models of ART adherence are emerging. The current study assessed the determinants of adherence behavior postulated by the Information–Motivation–Behavioral Skills model of ART adherence in a sample of 149 HIV-positive patients in Mississippi. Structural equation modeling indicated that ART-related information correlated with personal and social motivation, and the two sub-areas of motivation were not intercorrelated. In this Deep South sample, being better informed, socially supported, and perceiving fewer negative consequences of adherence were independently related to stronger behavioral skills for taking medications, which in turn associated with self-reported adherence. The IMB model of ART adherence appeared to well characterize the complexities of adherence for this sample.
Information; Motivation; Behavioral skills; ART adherence; Mississippi
Population-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.
To characterize the HIV sexual risk behaviors of patients with and without drug-resistant HIV in the clinical care setting over time.
393 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.
In 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.
In 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.
Although peer interventionists have been successful in medication treatment-adherence interventions, their role in complex behavior-change approaches to promote entry and reentry into HIV care requires further investigation. The current study sought to describe and test the feasibility of a standardized peer-mentor training program used for MAPPS (Mentor Approach for Promoting Patient Self-Care), a study designed to increase engagement and attendance at HIV outpatient visits among high-risk HIV inpatients using HIV-positive peer interventionists to deliver a comprehensive behavioral change intervention. Development of MAPPS and its corresponding training program included collaborations with mentors from a standing outpatient mentor program. The final training program included (1) a half-day workshop; (2) practice role-plays; and (3) formal, standardized patient role-plays, using trained actors with “real-time” video observation (and ratings from trainers). Mentor training occurred over a 6-week period and required demonstration of adherence and skill, as rated by MAPPS trainers. Although time intensive, ultimate certification of mentors suggested the program was both feasible and effective. Survey data indicated mentors thought highly of the training program, while objective rating data from trainers indicated mentors were able to understand and display standards associated with intervention fidelity. Data from the MAPPS training program provide preliminary evidence that peer mentors can be trained to levels necessary to ensure intervention fidelity, even within moderately complex behavioral-change interventions. Although additional research is needed due to limitations of the current study (e.g., limited generalizability due to sample size and limited breadth of clinical training opportunities), data from the current trial suggest that training programs such as MAPPS appear both feasible and effective.
Greater understanding of barriers to risk reduction among incarcerated HIV+ persons reentering the community is needed to inform culturally tailored interventions. This qualitative study elicited HIV prevention-related information, motivation and behavioral skills (IMB) needs of 30 incarcerated HIV+ men and women awaiting release from state prison. Unmet information needs included risk questions about viral loads, positive sexual partners, and transmission through casual contact. Social motivational barriers to risk reduction included partner perceptions that prison release increases sexual desirability, partners’ negative condom attitudes, and HIV disclosure-related fears of rejection. Personal motivational barriers included depression and strong desires for sex or substance use upon release. Behavioral skills needs included initiating safer behaviors with partners with whom condoms had not been used prior to incarceration, disclosing HIV status, and acquiring clean needles or condoms upon release. Stigma and privacy concerns were prominent prison context barriers to delivering HIV prevention services during incarceration.
Prison; Incarceration; HIV prevention; HIV-positive; Qualitative
Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.
We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC–TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.
The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57).
Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.)