<p>Adolescents with suboptimal medication taking may deceive caregivers about non-adherence. We conducted a 5-year longitudinal study of adolescents monitored simultaneously with both easily manipulated (e.g., self-report) and hard to manipulate (e.g., microelectronic data) strategies. Adolescents with repeatedly high adherence on the former and low adherence on the latter were invited along with their parental figures ("parents") to participate. We conducted focus groups and semi-structured interviews, separately for adolescents and parents, to elucidate drivers of discordant measures. Forty-seven adolescents and 26 parents participated in focus groups and 4 adolescents were interviewed. Adolescents described hiding pills, discarding pills, and lying. Their motivations included fear of disappointing those who care about them, desire to avoid admonishment by parents and clinic staff, and desire to avoid remedial adherence counseling. Both adolescents and parents considered negative feedback for prior poor adherence to be key motivation to hide current poor adherence from clinic staff. Providing positive feedback for truth-telling, rather than for "evidence" of excellent adherence, might help adolescent patients and their parents to develop stronger treatment alliances with each other and with clinic staff. Such alliances would allow adherence interventions to be better targeted and more fruitful in increasing adherence.</p>

<p>Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.</p>

<p><strong>PURPOSE: </strong>This study aimed to determine if disclosure of HIV status to adolescents impacted their medication adherence and how medication autonomy might explain observed effects.</p>

<p><strong>METHODS: </strong>Three hundred adolescents on HIV treatment using electronic medication monitors were followed for 24&nbsp;months while undergoing routine care. One hundred six of the adolescents were HIV disclosure-naïve and HIV status disclosure in this group was assessed quarterly. Analyses included data from the 75 adolescents who experienced disclosure during the study providing adherence and autonomy data both predisclosure and postdisclosure. Segmented generalized estimating equations were used to examine the trend of adherence and autonomy predisclosure and postdisclosure. Covariates assessed include age at disclosure, sex, and orphan status.</p>

<p><strong>RESULTS: </strong>Median age at study entry was 12.2&nbsp;years (interquartile range 11.6-12.9). Incident disclosure occurred in 75 (71%) of the adolescents at a median age of 13.1&nbsp;years (interquartile range 12.5-13.9). Adherence decreased by 11% (95% confidence interval [CI] 7-15, p &lt; .001) during the predisclosure period and by 22% (95% CI 9-36, p&nbsp;= .001) during the postdisclosure period. Adolescents' autonomy over their medication-taking increased over time, but disclosure did not impact the rate of increase in measured medication-taking autonomy. On a scale of 1-4 assessing autonomy (1&nbsp;= receiving directly observed therapy and 4&nbsp;= taking medicines mostly without supervision), autonomy increased by an average of .03 units/month (95% CI .02-.03, p &lt; .001) predisclosure and by .05 units/month (95% CI&nbsp;-.01 to .11, p&nbsp;= .42) postdisclosure.</p>

<p><strong>CONCLUSIONS: </strong>The findings suggest that, among perinatally HIV infected adolescents, HIV status disclosure may adversely impact treatment adherence. Postdisclosure support to HIV infected adolescents should be intensified.</p>

<p>In adults living with HIV, pharmacy refill data are good predictors of virologic failure (VF). The utility of pharmacy refill data for predicting VF in adolescents has not been reported. We evaluated data from 291 adolescents on antiretroviral therapy. The main outcome measure was VF, defined as two consecutive HIV viral load measurements ≥ 400 copies/mL during 24-months of follow-up. Pharmacy refill non-adherence was defined as two consecutive refill adherence measurements &lt; 95% during the same period. Fifty-three (18%) adolescents experienced VF. One hundred twenty-eight (44%) adolescents had refill non-adherence. Refill non-adherence had poor discriminative ability for indicating VF (receiver operating characteristic AUC = 0.60). Sensitivity and specificity for predicting VF was poor (60% (95% CI 46-74%) and 60% (95% CI 53-66%), respectively). The lack of a viable surrogate for VF in adolescents highlights the urgent need for more access to virologic testing and novel methods of monitoring adolescent treatment adherence.</p>

<p>Levels of adherence to HIV treatment are lower among adolescents compared with older and younger individuals receiving similar therapies. We purposely sampled the most and least adherent adolescents from a 300-adolescent longitudinal HIV treatment adherence study in Gaborone, Botswana. Multiple objective and subjective measures of adherence were available and study participants were selected based on sustained patterns of either excellent or poor adherence over a one-year period. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with the adolescents and a subset of their caregivers with the goal of revealing barriers and facilitators of adherence. Focus groups were segregated by adherence classification of the participants. Following coding of transcripts, matrices were developed based on participants' adherence classifications in order to clarify differences in themes generated by individuals with different adherence characteristics. 47 adolescents and 25 adults were included. The non-adherent adolescents were older than the adherent adolescents (median age 18 years (IQR 16-19) vs. 14 years (IQR 12-15 years)), with median time on treatment near 10 years in both groups. Interference with daily activities, concerns about stigma and discrimination, side effects, denial of HIV status, and food insecurity arose as challenges to adherence among both those who were consistently adherent and those who were poorly-adherent to their medications. Low outcome expectancy, treatment fatigue, mental health and substance use problems, and mismatches between desired and received social support were discussed only among poorly adherent adolescents and their caregivers. Challenges raised only among adolescents and caregivers in the non-adherent groups are hypothesis-generating, identifying areas that may have a greater contribution to poor outcomes than challenges faced by both adherent and non-adherent adolescents. The contribution of these factors to poor outcomes should be explored in future studies.</p>

<p>We hypothesized that longer and more frequent dosing gaps among boys in Botswana taking antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection compared to girls could account for previously seen gender-specific differences in outcomes. We monitored 154 male and 134 female adolescents for 2&nbsp;years with medication event monitoring systems (MEMS). Median adherence was 95.6&nbsp;% for males and 95.7&nbsp;% for females (p&nbsp;=&nbsp;0.40). There were no significant gender differences in the number of ≥7&nbsp;day (p&nbsp;=&nbsp;0.55) and ≥14&nbsp;day (p&nbsp;=&nbsp;0.48) dosing gaps. The median maximal gap was 7.7&nbsp;days for males and 8.0&nbsp;days for females (p&nbsp;=&nbsp;0.47). These findings are not consistent with clinically meaningful gender differences in adherence.</p>

<p><strong>STUDY OBJECTIVES: </strong>Psychosocial factors such as outcome expectancy, perceived stigma, socio-emotional support, consideration of future consequences, and psychological reactance likely influence adolescent adherence to antiretroviral treatments. Culturally-adapted and validated tools for measuring these factors in African adolescents are lacking. We aimed to identify culturally-specific factors of importance to establishing local construct validity in Botswana.</p>

<p><strong>METHODS: </strong>Using in-depth interviews of 34 HIV+ adolescents, we explored how the psychosocial factors listed above are perceived in this cultural context. We evaluated six scales that have been validated in other contexts. We also probed for additional factors that the adolescents considered important to their HIV medication adherence. Analyses were conducted with an analytic framework approach using NVivo9 software.</p>

<p><strong>RESULTS: </strong>While the construct validity of some Western-derived assessment tools was confirmed, other tools were poorly representative of their constructs in this cultural context. Tools chosen to evaluate HIV-related outcome expectancy and perceived stigma were well-understood and relevant to the adolescents. Feedback from the adolescents suggested that tools to measure all other constructs need major modifications to obtain construct validity in Botswana. The scale regarding future consequences was poorly understood and contained several items that lacked relevance for the Batswana adolescents. They thought psychological reactance played an important role in adherence, but did not relate well to many components of the reactance scale. Measurement of socio-emotional support needs to focus on the adolescent-parent relationship, rather than peer-support in this cultural context. Denial of being HIV-infected was an unexpectedly common theme. Ambivalence about taking medicines was also expressed.</p>

<p><strong>DISCUSSION: </strong>In-depth interviews of Batswana adolescents confirmed the construct validity of some Western-developed psychosocial assessment tools, but demonstrated limitations in others. Previously underappreciated factors related to HIV medication adherence, such as denial and ambivalence, should be further explored.</p>

<p><strong>PURPOSE: </strong>The purpose of this study was to determine whether diary-driven adjustment of Medication Event Monitoring System (MEMS) data based on Supporting Information strengthens the relationship between measured antiretroviral medication adherence and plasma HIV viral load (VL).</p>

<p><strong>METHODS: </strong>HIV+ adolescents on antiretroviral treatment were monitored with MEMS for 30 days preceding a VL measurement. The primary outcome was VL ≥ 400 copies/mL. Handwritten diaries were used to comprehensively record deviations from recommended use (bottle opened but dose not taken or bottle not opened and dose taken). Data were adjusted ("cleaned") based on diary events. Data were "capped" at the prescribed number of doses/day. Receiver operator characteristic analysis compared the relationships between (i) raw MEMS data, (ii) diary-cleaned, (iii) capped, or (iv) cleaned and capped MEMS data and VL.</p>

<p><strong>RESULTS: </strong>Over 30 days preceding VL measurements, 273 adolescents had 465 diary events. Capping resulted in fewer patients classified as 95% adherent (65.2%) compared with raw data (71.4%), p &lt; 0.001. Adherence was highly associated with VL (OR 1.05, p &lt; 0.001). The area under the receiver operating characteristic curve for continuous adherence compared with VL was 0.89 (95%CI: 0.82-0.95). Neither diary-cleaning, capping, nor cleaning and capping MEMS data significantly altered the association between adherence and VL (p = 0.14, 0.40, and 0.19, respectively).</p>

<p><strong>CONCLUSION: </strong>Medication Event Monitoring System data-cleaning based on diary entries did not affect the adherence-VL relationship. Copyright © 2015 John Wiley &amp; Sons, Ltd.</p>

<p>Pill counts with calculated adherence percentages are used in many settings to monitor adherence, but can be undermined by patients discarding pills to hide non-adherence. Pill counts suggesting that &gt;100% of prescribed doses were taken can signal "pill dumping." We defined "over-adherence" (OA) among a cohort of 300 HIV-infected adolescents as having &gt;1/3 of pill counts with &gt;100% adherence during a year of follow-up. Apparent over-adherence was more common in those with virologic failure than those with suppressed viral loads (33% vs 13%, chi p=0.001). Pill count adherence repeatedly &gt;100% may identify HIV-infected adolescents at increased risk of treatment failure.</p>

<p>Psychosocial dysfunction is a risk factor for treatment non-adherence among children and adolescents. A previous study showed that high scores on the Pediatric Symptom Checklist (PSC) were associated with a history of HIV virologic failure. We assessed whether high scores on the PSC could predict virologic failure in HIV-infected youth. Caregivers of 234 adolescents between the ages of 10 and 16&nbsp;years were asked to complete a PSC at baseline. Elevated PSC scores were associated with virologic failure in the subsequent 6&nbsp;months. PSC scores may help guide resource utilization when viral load monitoring is limited.</p>