Measure Of Antiretroviral Therapy Adherence Research Articles

Site-Level Comprehensiveness of Care Is Associated with Individual Clinical Retention Among Adults Living with HIV in International Epidemiology Databases to Evaluate AIDS, a Global HIV Cohort Collaboration, 2000-2016.

Retention in care (RIC) reduces HIV transmission and associated morbidity and mortality. We examined whether delivery of comprehensive services influenced individual RIC within the International epidemiology Databases to Evaluate AIDS (IeDEA) network. We collected site data through IeDEA assessments 1.0 (2000-2009) and 2.0 (2010-2016). Each site received a comprehensiveness score for service availability (1 = present, 0 = absent), with tallies ranging from 0 to 7. We obtained individual-level cohort data for adults with at least one visit from 2000 to 2016 at sites responding to either assessment. Person-time was recorded annually, with RIC defined as completing two visits at least 90 days apart in each calendar year. Multivariable modified Poisson regression clustered by site yielded risk ratios and predicted probabilities for individual RIC by comprehensiveness. Among 347,060 individuals in care at 122 sites with 1,619,558 person-years of follow-up, 69.8% of person-time was retained in care, varying by region from 53.8% (Asia-Pacific) to 82.7% (East Africa); RIC improved by about 2% per year from 2000 to 2016 (p = 0.012). Every site provided CD4+ count testing, and >90% of individuals received care at sites that provided combination antiretroviral therapy adherence measures, prevention of mother-to-child transmission, tuberculosis screening, HIV-related prevention, and community tracing services. In adjusted models, individuals at sites with more comprehensive services had higher probabilities of RIC (0.71, 0.74, and 0.83 for scores 5, 6, and 7, respectively; p = 0.019). Within IeDEA, greater site-level comprehensiveness of services was associated with improved individual RIC. Much work remains in exploring this relationship, which may inform HIV clinical practice and health systems planning.

A Single-Blind, Parallel Design RCT to Assess the Effectiveness of SMS Reminders in Improving ART Adherence Among Adolescents Living with HIV (STARTA Trial)

PurposeThe study evaluated the feasibility, acceptability, and efficacy of interactive and tailored short message reminders on antiretroviral therapy adherence among adolescents (15–19 years) living with HIV in southwest Nigeria. MethodsThe study was a single-blind, parallel-design (ratio 1:1), and multicenter RCT of 209 medication-non-adherent adolescents living with HIV at HIV clinics in two states in southwest Nigeria. The research assessed ART adherence using the visual analog scale, viral suppression, pill count, and ACTG scores; the feasibility of the intervention by the SMS delivery and response (overall and individual) rates; and acceptability using self-report, willingness to continue receiving the intervention, and desire for its scale-up. ResultsA total of 17,690 text messages were sent while 10,119 (57.2%) got delivered to the participants. Out of 9,216 responses that were received from the study participants, 8,781 (95.3%) indicated acceptability of the intervention.The end-of-study log10 of viral load values between control and intervention groups had a mean difference of 0.66 (95% CI 0.26–1.06) and p-value of .001. Also, the unadjusted odds ratio of undetected viral load (≤20 copies/ml) was 1.356 (1.039–1.771) with a p-value of .002. However, the intervention had no effect on subjective measures of antiretroviral therapy adherence. ConclusionsThe use of interactive and tailored short message reminders to enhance antiretroviral therapy adherence among adolescents has good potential. It seems feasible, highly acceptable, and possibly leads to improved viral load count. It is likely that the associated antiretroviral therapy adherence enhances viral suppression and, therefore, improves outcomes in adolescent HIV.

Using an Electronic Medication Event-Monitoring System for Antiretroviral Therapy Self-Management Among African American Women Living With HIV in Rural Florida: Cohort Study.

BackgroundHIV remains a significant health issue in the United States and disproportionately affects African Americans. African American women living with HIV (AAWH) experience a particularly high number of barriers when attempting to manage their HIV care, including antiretroviral therapy (ART) adherence. To enable the development and assessment of effective interventions that address these barriers to support ART adherence, there is a critical need to understand more fully the use of objective measures of ART adherence among AAWH, including electronic medication dispensers for real-time surveillance.ObjectiveThis study aimed to evaluate the use of the Wisepill medication event–monitoring system (MEMS) and compare the objective and subjective measures of ART adherence.MethodsWe conducted a 30-day exploratory pilot study of the MEMS among a convenience sample of community-dwelling AAWH (N=14) in rural Florida. AAWH were trained on the use of the MEMS to determine the feasibility of collecting, capturing, and manipulating the MEMS data for an objective measure of ART adherence. Self-reported sociodemographic information, including a self-reported measure of ART adherence, was also collected from AAWH.ResultsWe found that the majority of participants were successful at using the electronic MEMS. Daily use of the MEMS tended to be outside of the usual time participants took their medication. Three 30-day medication event patterns were found that characterized ART adherence, specifically uniform and nonuniform medication adherence and nonuniform medication nonadherence. There were relatively few MEMS disruptions among study participants. Overall, adjusted daily ART adherence was 81.08% and subjective ART adherence was 77.78%.ConclusionsThis pilot study on the use and evaluation of the Wisepill MEMS among AAWH in rural Florida is the first such study in the United States. The findings of this study are encouraging because 10 out of 12 participants consistently used the MEMS, there were relatively few failures, and objective adjusted daily and overall subjective ART adherence were very similar. On the basis of these findings, we think researchers should consider using the Wisepill MEMS in future studies of AAWH and people living with HIV in the United States after taking into account our practical suggestions. The following practical considerations are suggested when measuring objective medication adherence: (1) before using an MEMS, be familiar with the targeted populations’ characteristics; (2) choose an MEMS that aligns with the participants’ day-to-day activities; (3) ensure the MEMS’ features and resulting data support the research goals; (4) assess the match among the user’s ability, wireless features of the MEMS, and the geographic location of the participants; and (5) consider the cost of MEMS and the research budget.

Preliminary Validation of an Unannounced Telephone Pill Count Protocol to Measure Medication Adherence Among Young Adults With Perinatal HIV Infection.

Unannounced telephone pill counts are an objective antiretroviral therapy adherence measurement tool, but this method has not been validated in young adults (YA) living with perinatal HIV infection. Perinatally infected YA, recruited from the Child and Adolescent Self-Awareness and Health Study, agreed to unannounced telephone pill counts to measure medication adherence over 4 months and phlebotomy to measure viral load (VL). Differences in pill count adherence scores among YA with a VL of ≤20 versus >20, and demographic differences were assessed. Participants (N = 62) were, on average, 24 years old; 57% were African American, and 40% were Latino. Participants with VL of ≤20 (60%) had significantly higher adherence scores (85% versus 62%; p = .004). Associations were not significant among older YA (range, 25-28 years) or Latinos. Unannounced telephone pill counts are a valid measure of antiretroviral therapy adherence in YA with perinatal HIV infection. Studies with larger samples are needed.

Detecting Disengagement From HIV Care Before It Is Too Late: Development and Preliminary Validation of a Novel Index of Engagement in HIV Care.

Engagement in care is critical to achieving and sustaining optimal benefits of efficacious antiretroviral therapies for HIV infection. Current metrics of engagement in care, including problematic patterns of retention in care, adherence to treatment, and viral suppression, are often detected late in the disengagement process. We sought to develop and validate a patient-centered screener of engagement in care that can be used to identify deficits in patient perceptions of engagement before the development of poor outcomes, including loss to follow-up, treatment nonadherence, virologic failure, and the resulting increased likelihood of HIV-associated morbidity and mortality and onward transmission of HIV. Using input from patients, providers, and researchers through in-person focus groups and an online Delphi process, we developed a self-report measure of engagement in care that was validated with 3296 patients from 7 clinics across the United States. Results supported a single dimension of engagement in care measured by 10 items. Lower scores on the HIV Index were related to higher depression and anxiety symptoms, greater use of alcohol and stimulants, and increased likelihood of reporting internalized HIV stigma. Higher Index scores were positively associated with self-report measures of antiretroviral therapy adherence, corroborative clinic records documenting appointment attendance, and increased likelihood of recent viral load suppression. The HIV Index offers promise as a patient-centered diagnostic and prognostic screener for engagement in care that can be used to trigger interventions to promote better clinical outcomes for persons living with HIV.

If You Build It, Will They Use It? Preferences for Antiretroviral Therapy (ART) Adherence Monitoring Among People Who Inject Drugs (PWID) in Kazakhstan.

Adherence to antiretroviral therapy (ART) is an important predictor of long-term treatment success and is associated with optimal individual and public health outcomes. Novel technologies, such as electronic monitoring devices (EMDs) or pharmacokinetic testing, provide more objective measures of ART adherence than traditional measures of adherence (e.g., self-report) and may facilitate improved adherence through the provision of patient feedback. This study examines preferences for ART adherence monitoring among people who inject drugs (PWID) in Kazakhstan. In-depth interviews were conducted with 20 HIV-positive PWID, 18 of their intimate partners, and 7 AIDS Center healthcare providers in Almaty, Kazakhstan. Results indicated that patients varied in their preferences of which strategies would be most effective and acceptable to use in monitoring their adherence. Overall, patients were highly enthusiastic about the potential use of pharmacokinetic testing. Many participants supported the use of EMDs, though some were concerned about having their adherence tracked. Other participants thought reminders through text messaging or smart phone applications would be helpful, though several had concerns about confidentiality and others worried about technological difficulties operating a smart phone. Future studies should evaluate the feasibility and impact of providing quantitative drug levels as feedback for ART adherence using biomarkers of longer-term ART exposure, (i.e., hair sampling or dried blood spot testing).

What Can Urine Tell Us About Medication Adherence?

What Can Urine Tell Us About Medication Adherence?

Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable’ viral load (<400copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as “never” for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

BackgroundThe adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.MethodsAmong adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.ResultsAmong 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01). When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.ConclusionsPharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

6.0 Supporting patients on therapy

6.0 Supporting patients on therapy

Evaluation of an affordable HIV-1 virological failure assay and antiretroviral drug resistance genotyping protocol

HIV-1 RNA viral load is the preferred tool to monitor virological failure during antiretroviral therapy (ART) exposure. Timely detection of virological failure can reduce the prevalence and complexity of HIV-1 drug resistance. This field evaluation further characterizes a two-step approach to identify virological failure, as a measure of ART adherence, and detect HIVDR mutations in the reverse transcriptase (RT) gene of HIV-1. Two hundred and forty-eight (248) samples were tested; 225 from South African HIV-1 participants enrolled in the PharmAccess African Studies to Evaluate Resistance (PASER) cohort, forty of which had paired dried blood spot (DBS) samples and 23 HIV-1 negative samples. A newly developed virological failure assay (ARTA-VFA) was used on all samples, and those with a viral load >5000 RNA copies/ml were genotyped with a shortened RT protocol to detect HIVDR (ARTA-HIVDRultralight). The ARTA-VFA showed good precision and linearity as compared to a commercial reference assay (NucliSENS® EasyQ v1.2, Roche) with an R2 of 0.99. Accuracy studies illustrated standard deviations of <1 log RNA copies/ml for plasma and DBS ARTA-VFA results compared to the reference method. The ARTA-VFA's intended use was to deliver qualitative results either < or >5000 RNA copies/ml. No significant differences in the proportion of results < or > either the 5000 RNA copies/ml or 1000 RNA copies/ml cut-off were noted for plasma indicating either cut-off to be useful. Significant differences were noted in these proportions when DBS were used (P=0.0002), where a 5000 RNA copies/ml cut-off was deemed more appropriate. The sensitivity and specificity of the ARTA-VFA with plasma were 95% and 93% and 91% and 95% for DBS using a 5000 RNA copies/ml cut-off. The ARTA HIVDRultralight assay was reliable for plasma and DBS samples with a viral load >5000 RNA copies/ml, with amplification and sequencing success rates of 91% and 92% respectively for plasma, and 95% and 80% respectively for DBS. HIVDR profiles for plasma and DBS were 100% concordant with the reference assay. This study evaluated a previously described combination of two assays potentially useful in assessing HIV-1 virological failure and resistance, showing good concordance with reference assays. These assays are simple to perform and are affordable, viable options to detect virological failures in certain resource limited settings. The assays’ compatibility with DBS sampling extends the access of HIV-1 virological monitoring to more remote settings.

Does Antiretroviral Therapy Interfere With the Treatment of Trichomonas vaginalis Among HIV+ Women?

Does Antiretroviral Therapy Interfere With the Treatment of Trichomonas vaginalis Among HIV+ Women?

Developing Useful Highly Active Antiretroviral Therapy Adherence Measures for India: The Prerana Study

This letter to the editor focuses on a study that was designed to address the impact of adherence on viral load the predictive validity of combined measures and the relationship between multiple adherence measures. The study addresses this gap by assessing the relationship between multiple self-reported adherence measures and HIV viral suppression in a longitudinal cohort of HIV-infected patients in Bangalore India.

Use of a prescription‐based measure of antiretroviral therapy adherence to predict viral rebound in HIV‐infected individuals with viral suppression

The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients. The analysis was performed on the Royal Free HIV Cohort, London, UK. Each 'drug coverage-viral load episode' (DCVL episode) was defined as a 6-month period immediately prior to a VL < or =50 HIV-1 RNA copies/mL (time-zero), during which the patient had been continuously on HAART, with all measured VLs < or =50 copies/mL. The next VL after time-zero was used to assess whether VL rebound (defined as >200 copies/mL) had occurred. Drug coverage, our measure of adherence, was calculated as the proportion of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs. A total of 376 (2.4%) VL rebounds occurred in 15 660 DCVL episodes among 1632 patients. Drug coverage was 100% for 32% of episodes, 95-99% for 16% of episodes and < or =60% for 10% of episodes. The risk ratio of rebound associated with a 10% increase in drug coverage, adjusted for potential confounding variables, was 0.93 (95% confidence interval 0.88-0.98). Antiretroviral drug coverage assessed at the time of VL measurement in patients with undetectable VL is potentially clinically useful for predicting VL rebound at the next VL measurement.

Preventing HIV Antiretroviral Resistance through Better Monitoring of Treatment Adherence

Suboptimal adherence to antiretroviral therapy (ART) is the most common cause of viral rebound. Accurate and reliable measures of ART adherence will be needed in the transition from reactive response to proactive prevention of viral rebound in the era of chronic human immunodeficiency virus (HIV) disease management. Such tools could define individual "signature adherence patterns," which could inform regimen choice and guide behavioral intervention. Upcoming advances in adherence monitoring present opportunities to better match HIV-disease treatment strategies with individual adherence behavior.

A Simple, Dynamic Measure of Antiretroviral Therapy Adherence Predicts Failure to Maintain HIV‐1 Suppression

High levels of antiretroviral therapy adherence are important for human immunodeficiency virus type 1 (HIV-1) suppression, yet the magnitude of adherence required to maintain it is less well characterized. Furthermore, methods to accommodate changes in adherence over time are lacking. In the present study, our objective was to determine the magnitude of antiretroviral therapy adherence needed to maintain HIV-1 suppression by use of a time-updated adherence measure that has the potential to be of use in a clinical setting. We examined a population-based cohort of HIV-1-infected subjects > or =18 years of age, residing in British Columbia, Canada, who started receiving antiretroviral therapy between 1 August 1996 and 30 September 2003, who had at least 2 consecutive viral loads <500 copies/mL and who had prescriptions filled at least 3 times during a follow-up period ending 30 September 2004. Virological failure was defined as the second of 2 consecutive viral loads >1000 copies/mL. Cox proportional hazards model was used to determine the relationship between virological failure and refill-based, time-updated surrogate measure of adherence. Among the 1634 participants > or =18 years of age who initiated triple combination therapy during the study, 606 virological failure events were identified. In multivariate analyses, subjects with < or =95% adherence were 1.66 (95% confidence interval, 1.38-2.01) times more likely to experience virological failure than those with >95% adherence. The highest levels of antiretroviral therapy adherence are associated with higher rates of maintained virological suppression. This simple, dynamic surrogate measure of adherence overcomes the limitation of single-point-in-time calculations of adherence and may be useful in real time to determine whether an individual is exhibiting incomplete adherence.

Self-Report Measures of Antiretroviral Therapy Adherence: A Review with Recommendations for HIV Research and Clinical Management

A review of 77 studies employing self-report measures of antiretroviral adherence published 1/1996 through 8/2004 revealed great variety in adherence assessment item content, format, and response options. Recall periods ranged from 2 to 365 days (mode = 7 days). The most common cutoff for optimal adherence was 100% (21/48 studies, or 44%). In 27 of 34 recall periods (79%), self-reported adherence was associated with adherence as assessed with other indirect measures. Data from 57 of 67 recall periods (84%) indicated self-reported adherence was significantly associated with HIV-1 RNA viral load; in 16 of 26 (62%), it was associated with CD4 count. Clearly, the field would benefit from item standardization and a priori definitions and operationalizations of adherence. We conclude that even brief self-report measures of antiretroviral adherence can be robust, and recommend items and strategies for HIV research and clinical management.

A time-to-prescription-refill measure of antiretroviral adherence predicted changes in viral load in HIV

Objective The goal of this study was to determine the validity and utility of a pharmacy-based time-to-refill measure of antiretroviral therapy adherence. Methods We performed an observational cohort study of 110 HIV-infected subjects on a stable, highly active antiretroviral regimen for at least 3 months at a Veterans' Affairs Medical Center in Philadelphia, Pennsylvania. Results The viral load decreased by 0.12 log c/mL (95% confidence interval [CI] 0.01–0.23 log c/mL) for each 10% increase in pharmacy-based time-to-refill defined adherence as compared with 0.05 log c/mL (95% CI −0.14–0.25 log c/mL) for the self-reported adherence measure. Thus, only the refill-defined measure was statistically significantly associated with viral load change. When adherence was classified as good (≥85%) versus poor (<85%), both measures demonstrated a significant difference in outcome between groups. Yet, in individuals self-reporting 100% adherence, those classified as good adherers using the pharmacy-based measure had greater viral load reductions than poor adherers (2.4 log c/mL [interquartile range 1.4–3.4] vs. 1.5 log c/mL [interquartile range 0.8–2.4, P = .03). Conclusions The pharmacy-based technique is a valid measure of antiretroviral therapy adherence. Because it provides clinically relevant information in subjects who self-report 100% adherence, it should be incorporated into clinical practice and adherence research.