<p><strong>INTRODUCTION: </strong>Neurodevelopmental delays and cognitive impairments are common in youth living with HIV. Unfortunately, in resource-limited settings, where HIV infection impacts millions of children, cognitive and neurodevelopmental disorders commonly go undetected because of a lack of appropriate assessment instruments and local expertise. Here, we present a protocol to culturally adapt and validate the Penn Computerized Neurocognitive Battery (PennCNB) and examine its validity for detecting both advanced and subtle neurodevelopmental problems among school-aged children affected by HIV in resource-limited settings.</p>

<p><strong>METHODS AND ANALYSIS: </strong>This is a prospective, observational cohort study. The venue for this study is Gaborone, Botswana, a resource-limited setting with high rates of perinatal exposure to HIV and limited neurocognitive assessment tools and expertise. We aim to validate the PennCNB in this setting by culturally adapting and then administering the adapted version of the battery to 200 HIV-infected, 200 HIV-exposed uninfected and 240 HIV-unexposed uninfected children. A series of analyses will be conducted to examine the reliability and construct validity of the PennCNB in these populations.</p>

<p><strong>ETHICS AND DISSEMINATION: </strong>This project received ethical approval from local and university Institutional Review Boards and involved extensive input from local stakeholders. If successful, the proposed tools will provide practical screening and streamlined, comprehensive assessments that could be implemented in resource-limited settings to identify children with cognitive deficits within programmes focused on the care and treatment of children affected by HIV. The utility of such assessments could also extend beyond children affected by HIV, increasing general access to paediatric cognitive assessments in resource-limited settings.</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><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>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>