"I have never talked to anyone to free my mind" - challenges surrounding status disclosure to adolescents contribute to their disengagement from HIV care: a qualitative study in western Kenya.

INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) experience complex barriers to care engagement. Challenges surrounding HIV status disclosure or non-disclosure to adolescents may contribute to adolescent disengagement from HIV care or non-adherence to ART. We performed a qualitative study to investigate the contribution of disclosure challenges to adolescent disengagement from HIV care. METHODS: This was a qualitative study performed with disengaged ALHIV and their caregivers, and with healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya. Inclusion criteria for ALHIV were ≥1 visit within the 18 months prior to data collection at one of two clinical sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Analysis was conducted by multiple independent coders, and narratives of disclosure and care disengagement were closely interrogated. Overarching themes were elucidated and summarized. RESULTS: Interviews were conducted with 42 disengaged ALHIV, 32 caregivers, and 28 HCW. ALHIV were average age 17.0 (range 12.9-20.9), and 95% indicated awareness of their HIV diagnosis. Issues surrounding disclosure to ALHIV presented important barriers to HIV care engagement. Themes centered on delays in HIV status disclosure; hesitancy and reluctance among caregivers to disclose; struggles for adolescents to cope with feelings of having been deceived prior to full disclosure; pervasive HIV stigma internalized in school and community settings prior to disclosure; and inadequate and unstructured support after disclosure, including for adolescent mental health burdens and for adolescent-caregiver relationships and communication. Both HCW and caregivers described feeling inadequately prepared to optimally handle disclosure and to manage challenges that may arise after disclosure. CONCLUSIONS: Complex challenges surrounding HIV status disclosure to adolescents contribute to care disengagement. There is need to enhance training and resources for HCW, and to empower caregivers to support children and adolescents before, during, and after HIV status disclosure. This should include counseling caregivers on how to provide children with developmentally-appropriate and accurate information about their health from an early age, and to support adolescent-caregiver communication and relationships. Optimally integrating peer support can further promote ALHIV wellbeing and retention in care.

Tablet-based disclosure counselling for HIV-infected children, adolescents, and their caregivers: a pilot study.

BACKGROUND: Overwhelmed, under-trained medical staff working in resource-limited settings need efficient resources for HIV disclosure counselling. The objective of this study was to describe providers' experiences using tablet computers for disclosure-related counselling with HIV-infected children and their caregivers in western Kenya, with additional perspectives from adolescents. METHODS: A qualitative study design was implemented at three HIV clinics in western Kenya (Bumala, Busia and Port Victoria) within the Academic Model Providing Access to Healthcare (AMPATH) partnership. Twenty-one healthcare providers involved with paediatric disclosure were recruited and enrolled in the study. Initial interviews focused on understanding current disclosure practices and barriers. Tablets containing disclosure-related resources were distributed. Resources included short narrative videos created in this context to highlight issues relevant to child HIV disclosure. RESULTS: Providers reported tablets improved disclosure, child participation, and medication adherence. All reported that reviewing materials increased their knowledge and comfort with disclosure. The most frequently used materials were the narrative videos and an animated video explaining the importance of medication adherence. Time was a major barrier for using the tablet. Clinician self-education persisted at one-year follow-up. Adolescents expressed enjoyment from viewing the tablet resources and had a better understanding of the importance of medication adherence. CONCLUSIONS: Tablet computers containing resources for disclosure are an acceptable and potentially effective resource to help providers support families with disclosure. Further work is needed to train the clinical providers in using the resources in a developmentally appropriate manner, and to develop new resources on adolescent-specific and HIV-related topics.

Comprehensive evaluation of caregiver-reported antiretroviral therapy adherence for HIV-infected children.

For HIV-infected children, adherence to antiretroviral therapy (ART) is often assessed by caregiver report but there are few data on their validity. We conducted prospective evaluations with 191 children ages 0-14 years and their caregivers over 6 months in western Kenya to identify questionnaire items that best predicted adherence to ART. Medication Event Monitoring Systems(®) (MEMS, MWV/AARDEX Ltd., Switzerland) electronic dose monitors were used as external criterion for adherence. We employed a novel variable selection tool using the LASSO technique with logistic regression to identify items best correlated with dichotomized MEMS adherence (≥90 or <90 % doses taken). Nine of 48 adherence items were identified as the best predictors of adherence, including missed or late doses in the past 7 days, problems giving the child medicines, and caregiver-level factors like not being present at medication taking. These items could be included in adherence assessment tools for pediatric patients.

Characteristics of HIV-infected adolescents enrolled in a disclosure intervention trial in western Kenya.

Knowledge of one's own HIV status is essential for long-term disease management, but there are few data on how disclosure of HIV status to infected children and adolescents in sub-Saharan Africa is associated with clinical and psychosocial health outcomes. We conducted a detailed baseline assessment of the disclosure status, medication adherence, HIV stigma, depression, emotional and behavioral difficulties, and quality of life among a cohort of Kenyan children enrolled in an intervention study to promote disclosure of HIV status. Among 285 caregiver-child dyads enrolled in the study, children's mean age was 12.3 years. Caregivers were more likely to report that the child knew his/her diagnosis (41%) compared to self-reported disclosure by children (31%). Caregivers of disclosed children reported significantly more positive views about disclosure compared to caregivers of non-disclosed children, who expressed fears of disclosure related to the child being too young to understand (75%), potential psychological trauma for the child (64%), and stigma and discrimination if the child told others (56%). Overall, the vast majority of children scored within normal ranges on screenings for behavioral and emotional difficulties, depression, and quality of life, and did not differ by whether or not the child knew his/her HIV status. A number of factors were associated with a child's knowledge of his/her HIV diagnosis in multivariate regression, including older age (OR 1.8, 95% CI 1.5-2.1), better WHO disease stage (OR 2.5, 95% CI 1.4-4.4), and fewer reported caregiver-level adherence barriers (OR 1.9, 95% CI 1.1-3.4). While a minority of children in this cohort knew their HIV status and caregivers reported significant barriers to disclosure including fears about negative emotional impacts, we found that disclosure was not associated with worse psychosocial outcomes.

Cognitive interviewing for cross-cultural adaptation of pediatric antiretroviral therapy adherence measurement items.

BACKGROUND: There are 2.3 million children living with HIV worldwide, almost 90 % of whom live in sub-Saharan Africa. Access to antiretroviral therapy (ART) for HIV treatment has dramatically increased in resource-limited settings in recent years and allows more HIV-infected children to survive into adolescence and adulthood. PURPOSE: Our objective was to improve the understandability of pediatric antiretroviral adherence measurement items for use in resource-limited settings through cognitive interviewing with pediatric caregivers and HIV-infected adolescents in Kenya. METHODS: We compiled adherence measurement items through a systematic literature review and qualitative work. We conducted cognitive interviews assessing the items with caregivers of HIV-infected children enrolled in HIV care in Kenya and conducted group cognitive assessments with HIV-infected adolescents. We used verbal probing and guided "thinking aloud" to evaluate relevance, comprehension, recall, and sensitivity/acceptability. Analysis followed a systematic sequence of review, compiling data by item, and coding responses. RESULTS: We interviewed 21 Kenyan parents and guardians and 10 adolescents (mean age 15 years, SD 1.8) on antiretroviral therapy for a mean of 3.6 years. Cognitive interviews optimized item-response options, wording, and content. Some participants demonstrated difficulty with "think aloud" processes, but verbal probes were easily answered. Comprehension problems were found for key language concepts such "missed doses" and "having side effects." Key findings for response options included differences among responses to various recall periods, with preferences for the shortest (one 24-h day) and longest recall periods (1 month); difficulty describing specific drug information; benefits for including normalizing statements before asking for sensitive information; and challenges processing categorical frequency scales. Important content areas for inclusion included dose timing, disclosure, stigma, and food insecurity. CONCLUSIONS: Cognitive interviewing is a productive strategy for increasing the face validity and understandability of adherence measurement items, particularly across cultures. Interviews in Kenya suggested adherence measurement modifications of relevance for other resource-limited settings.

Understanding Women's Preferences for Prevention of Mother-to-Child HIV Transmission Services in Kenya.

Background and Objective: Understanding the preferences of women living with HIV (WLH) for the prevention of mother-to-child HIV transmission (PMTCT) services is important to ensure such services are person-centered. Methods: From April to December 2022, we surveyed pregnant and postpartum WLH enrolled at five health facilities in western Kenya to understand their preferences for PMTCT services. WLH were stratified based on the timing of HIV diagnosis: known HIV-positive (KHP; before antenatal clinic [ANC] enrollment), newly HIV-positive (NHP; on/after ANC enrollment). Multivariable logistic regression was used to determine associations between various service preferences and NHP (vs. KHP) status, controlling for age, facility, gravidity, retention status, and pregnancy status. Results: Among 250 participants (median age 31 years, 31% NHP, 69% KHP), 93% preferred integrated versus non-integrated HIV and maternal-child health (MCH) services; 37% preferred male partners attend at least one ANC appointment (vs. no attendance/no preference); 54% preferred support groups (vs. no groups; 96% preferred facility - over community-based groups); and, preferences for groups was lower among NHP (42%) versus KHP (60%). NHP had lower odds of preferring support groups versus KHP (aOR 0.45, 95% CI 0.25-0.82), but not the other services. Conclusion and Global Health Implications: Integrated services were highly preferred by WLH, supporting the current PMTCT service model in Kenya. Further research is needed to explore the implementation of facility-based support groups for WLH as well as the reasons underlying women's preferences.

Population Pharmacokinetics of Pediatric Lopinavir/Ritonavir Oral Pellets in Children Living with HIV in Africa.

Antiretroviral therapy for children living with HIV (CLHIV) under 3 years of age commonly includes lopinavir/ritonavir (LPV/r). However, the original liquid LPV/r formulation has taste and cold storage difficulties. To address these challenges, LPV/r oral pellets have been developed. These pellets can be mixed with milk or food for administration and do not require refrigeration. We developed the population pharmacokinetic (PK) model and assessed drug exposure of LPV/r oral pellets administered twice daily to CLHIV per World Health Organization (WHO) weight bands. The PK analysis included Kenyan and Ugandan children participating in the LIVING studies (NCT02346487) receiving LPV/r pellets (40/10 mg) and ABC/3TC (60/30 mg) dispersible tablets. Population PK models were developed for lopinavir (LPV) and ritonavir (RTV) to evaluate the impact of RTV on the oral clearance (CL/F) of LPV. The data obtained from the study were analyzed using nonlinear mixed-effects modeling approach. Data from 514 children, comprising a total of 2,998 plasma concentrations of LPV/r were included in the analysis. The LPV and RTV concentrations were accurately represented by a one-compartment model with first-order absorption (incorporating a lag-time) and elimination. Body weight influenced LPV and RTV PK parameters. The impact of RTV concentrations on the CL/F of LPV was characterized using a maximum effect model. Simulation-predicted target LPV exposures were achieved in children with this pellet formulation across the WHO weight bands. The LPV/r pellets dosed in accordance with WHO weight bands provide adequate LPV exposures in Kenyan and Ugandan children weighing 3.0 to 24.9 kg.

Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands.

BACKGROUND: The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing <14 kg and receiving pediatric fixed dose combinations (FDC) according to WHO weight bands dosing are limited. An ABC population pharmacokinetic model was developed to evaluate ABC exposure across different World Health Organization (WHO) weight bands. METHODS: Children enrolled in the LIVING study in Kenya and Uganda receiving ABC/lamivudine (3TC) dispersible tablets (60/30 mg) according to WHO weight bands. A population approach was used to determine the pharmacokinetic parameters. Monte Carlo simulations were conducted using an in silico population with demographic characteristics associated with African CLHIV. ABC exposures (AUC0-24) of 6.4-50.4 mg h/L were used as targets. RESULTS: Plasma samples were obtained from 387 children. A 1-compartment model with allometric scaling of clearance (CL/F) and volume of distribution (V/F) according to body weight best characterized the pharmacokinetic data of ABC. The maturation of ABC CL/F was characterized using a sigmoidal Emax model dependent on postnatal age (50% of adult CL/F reached by 0.48 years of age). Exposures to ABC were within the target range for children weighing 6.0-24.9 kg, but children weighing 3-5.9 kg were predicted to be overexposed. CONCLUSIONS: Lowering the ABC dosage to 30 mg twice daily or 60 mg once daily for children weighing 3-5.9 kg increased the proportion of children within the target and provided comparable exposures. Further clinical study is required to investigate clinical implications and safety of the proposed alternative ABC doses.

Reciprocal innovation: A new approach to equitable and mutually beneficial global health partnerships.

Global health researchers often discount mutual learning and benefit to address shared health challenges across high and low- and middle-income settings. Drawing from a 30-year partnership called AMPATH that started between Indiana University in the US and Moi University in Kenya, we describe an innovative approach and program for mutual learning and benefit coined 'reciprocal innovation.' Reciprocal innovation harnesses a bidirectional, co-constituted, and iterative exchange of ideas, resources, and innovations to address shared health challenges across diverse global settings. The success of AMPATH in Kenya, particularly in HIV/AIDS and community health, resulted in several innovations being 'brought back' to the US. To promote the bidirectional flow of learning and innovations, the Indiana CTSI reciprocal innovation program hosts annual meetings of multinational researchers and practitioners to identify shared health challenges, supports pilot grants for projects with reciprocal exchange and benefit, and produces educational and training materials for investigators. The transformative power of global health to address systemic health inequities embraces equitable and reciprocal partnerships with mutual benefit across countries and communities of academics, practitioners, and policymakers. Leveraging a long-standing partnership, the Indiana CTSI has built a reciprocal innovation program with promise to redefine global health for shared wellbeing at a global scale.

"Who am I going to stay with? Who will accept me?": family-level domains influencing HIV care engagement among disengaged adolescents in Kenya.

INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) have developmentally specific needs in care, and have lower retention compared to other age groups. Family-level contexts may be critical to adolescent HIV outcomes, but have often been overlooked. We investigated family-level factors underlying disengagement and supporting re-engagement among adolescents disengaged from HIV care. METHODS: Semi-structured interviews were performed with 42 disengaged ALHIV, 32 of their caregivers and 28 healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya, from 2018 to 2020. Disengaged ALHIV had ≥1 visit within the 18 months prior to data collection at one of two sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Transcripts were analysed through thematic analysis. A conceptual model for family-level domains influencing adolescent HIV care engagement was developed from these themes. RESULTS: Family-level factors emerged as central to disengagement. ALHIV-particularly those orphaned by the loss of one or both parents-experienced challenges when new caregivers or unstable living situations limited support for HIV care. These challenges were compounded by anticipated stigma; resultant non-disclosure of HIV status to household members; enacted stigma in the household, with overwhelming effects on adolescents; or experiences of multiple forms of trauma, which undermined HIV care engagement. Some caregivers lacked finances or social support to facilitate care. Others did not feel equipped to support adolescent engagement or adherence. Regarding facilitators to re-engagement, participants described roles for household disclosure; and solidarity from caregivers, especially those also living with HIV. Family-level domains influencing HIV care engagement were conceptualized as follows: (1) adolescent living situation and contexts; (2) household material resources or poverty; (3) caregiver capacities and skills to support adolescent HIV care; and (4) HIV stigma or solidarity at the household level. CONCLUSIONS: Family-level factors are integral to retention in care for ALHIV. The conceptual model developed in this study for family-level influences on care engagement may inform holistic approaches to promote healthy outcomes for ALHIV. Developmentally appropriate interventions targeting household relationships, disclosure, HIV stigma reduction, HIV care skills and resources, and economic empowerment may promote adolescent engagement in HIV care.

Rooting inquiry in tradition: the health baraza as a tool for social research in Kenya.

The baraza is a customary form of community assembly in East Africa. We examined the use of the health baraza as a process that can improve data collection and deepen community understanding of sociocultural issues surrounding HIV/AIDS. In the evaluation of the United States Agency for International Development (USAID)-Academic Model for Prevention and Treatment of HIV/AIDS Partnership (USAID-AMPATH) in Kenya, investigators facilitated mabaraza (the plural of baraza) to gather information of relevance to program success, improvement, and community collaboration. Seven mabaraza were held at local health facilities. Mabaraza rapidly evoked essential information for the USAID-AMPATH program and facilitated vibrant discussion of themes that were of interest to local communities. Mabaraza combined individual and community outlooks, producing emic understanding of the program's meaning to local populations. The baraza assemblage is a promising technique for applied sociology, participatory research, and program evaluation.

"I just keep quiet about it and act as if everything is alright" - The cascade from trauma to disengagement among adolescents living with HIV in western Kenya.

INTRODUCTION: There are approximately 1.7 million adolescents living with HIV (ALHIV, ages 10 to 19) globally, including 110,000 in Kenya. While ALHIV experience poor retention in care, limited data exist on factors underlying disengagement. We investigated the burden of trauma among disengaged ALHIV in western Kenya, and its potential role in HIV care disengagement. METHODS: We performed in-depth qualitative interviews with ALHIV who had disengaged from care at two sites, their caregivers and healthcare workers (HCW) at 10 sites, from 2018 to 2020. Disengagement was defined as not attending clinic ≥60 days past a missed scheduled visit. ALHIV and their caregivers were traced through phone calls and home visits. Interviews ascertained barriers and facilitators to adolescent retention in HIV care. Dedicated questions elicited narratives surrounding traumatic experiences, and the ways in which these did or did not impact retention in care. Through thematic analysis, a conceptual model emerged for a cascade from adolescent experience of trauma to disengagement from HIV care. RESULTS: Interviews were conducted with 42 disengaged ALHIV, 34 caregivers and 28 HCW. ALHIV experienced a high burden of trauma from a range of stressors, including experiences at HIV disclosure or diagnosis, the loss of parents, enacted stigma and physical or sexual violence. A confluence of factors - trauma, stigma and isolation, and lack of social support - led to hopelessness and depression. These factors compounded each other, and resulted in complex mental health burdens, poor antiretroviral adherence and care disengagement. HCW approaches aligned with the factors in this model, suggesting that these areas represent targets for intervention and provision of trauma-informed care. CONCLUSIONS: Trauma is a major factor underlying disengagement from HIV care among Kenyan adolescents. We describe a cascade of factors representing areas for intervention to support mental health and retention in HIV care. These include not only the provision of mental healthcare, but also preventing or addressing violence, trauma and stigma, and reinforcing social and familial support surrounding vulnerable adolescents. In this conceptualization, supporting retention in HIV care requires a trauma-informed approach, both in the individualized care of ALHIV and in the development of strategies and policies to support adolescent health outcomes.

Early cardiac dysfunction in children and young adults with perinatally acquired HIV.

OBJECTIVE: To define the prevalence of early cardiac dysfunction in children and young adults with perinatally acquired HIV and predictors of cardiac function. DESIGN: Cross-sectional design. METHODS: Early cardiac dysfunction was defined as left ventricular (LV) global longitudinal strain z-score less than -2 or myocardial performance index at least 0.5 with normal LV ejection fraction. Regression models were fitted to assess the relationship between measures of cardiac function and HIV RNA levels, clinical variables, and markers of inflammation. RESULTS: Six hundred and forty-three individuals (mean age 14.1 ±â€Š5.2 years) were enrolled. The average time on combination antiretroviral treatment was 6.8 ±â€Š3.6 years. Nearly 28% of individuals met criteria for early cardiac dysfunction. Individuals with early cardiac dysfunction were older (15.3 vs. 13.5 years, P < 0.001), had more frequently detectable HIV RNA (52.5 vs. 41.7%, P = 0.018), were more likely exposed to azidothymidine or zidovudine (ZDV) (55.6 vs. 41.2%, P = 0.002), and had higher median level of plasma IL-6 concentrations (1.00 vs. 0.88 pg/ml, P = 0.011). Multivariable models show LV ejection fraction negatively associated with HIV RNA levels [ß -0.18; 95% confidence interval (CI) -0.33, -0.03] and ZDV exposure (ß -1.75; 95% CI -2.62, -0.88) and positively associated with proportion of life on combination antiretroviral treatment (ß 2.65; 95% CI 0.90, 4.41). Higher myocardial performance index was positively associated with serum inflammation marker (IL-6 ß 0.01; 95% CI 0.0001, 0.001). Left ventricular global longitudinal strain was not significantly associated with clinical and laboratory variables of interest. CONCLUSION: Over one-quarter of children and young adults living with HIV demonstrated evidence of cardiac dysfunction, which may be associated with increasing levels of systemic inflammation.

Factors sustaining pediatric adherence to antiretroviral therapy in western Kenya.

Antiretroviral therapy (ART) requires nearly perfect adherence to be effective. Although 90% of HIV-infected children live in Africa, there are limited data on pediatric adherence from this multicultural continent.We conducted a qualitative study to identify key factors contributing to pediatric ART adherence. Ten focus group discussions (N = 85) and 35 individual interviews were conducted with parents and guardians of HIV-infected children receiving ART in western Kenya. Interviews covered multiple aspects of the experience of having children take ART and factors that inhibited or facilitated medication adherence. Constant comparison, progressive coding, and triangulation methods were used to arrive at a culturally contextualized, conceptual model for pediatric ART adherence derived from the descriptions of the lived experience in this resource-limited setting. Child care, including sustained ART adherence, depends on interacting cultural and environmental determinants at the levels of the individual child, parent/caregiver, household, community, health care system, and society.

Evaluating a patient-centred intervention to increase disclosure and promote resilience for children living with HIV in Kenya.

OBJECTIVE: We evaluated the impact of a patient-centred, culturally and age-appropriate disclosure counselling intervention on HIV disclosure rates among Kenyan children living with HIV. DESIGN: A prospective, clinic-cluster randomized trial. METHODS: We followed 285 child-caregiver dyads (children ages 10-14 years) attending eight HIV clinics (randomized to intervention or control) in Kenya. Participants at intervention clinics received intensive counselling with trained disclosure counsellors and culturally tailored materials, compared with control clinics with standard care. Disclosure was treated as a time-to-event outcome, measured on a discrete time scale, with assessments at 0, 6, 12, 18 and 24 months. Mental health and behavioural outcomes were assessed using standardized questionnaires. RESULTS: Mean age was 12.3 years [standard deviation (SD) 1.5], 52% were girls, with average time-on-treatment of 4.5 years (SD 2.4). Between 0 and 6 months, disclosure prevalence increased from 47 to 58% in the control group and from 50 to 70% in the intervention group. Differences in disclosure were not sustained over the following 18 months. The prevalence of depression symptoms was significantly higher in the intervention than in the control group at 6 months (odds ratio 2.07, 95% confidence interval 1.01-4.25); however, there was no evidence that these differences were sustained after 6 months. CONCLUSION: The clinic-based intervention increased disclosure of HIV status to children living with HIV in the short-term, resulting in earlier disclosures, but had less clear impacts longer-term. Although well tailored interventions may support disclosure, children may still experience increased levels of depression symptoms immediately following disclosure.

Validation of a self-report adherence measurement tool among a multinational cohort of children living with HIV in Kenya, South Africa and Thailand.

INTRODUCTION: There are few data on adherence and low-cost measurement tools for children living with HIV. We collected prospective data on adherence to antiretroviral therapy (ART) among a multinational cohort of children to evaluate an adherence questionnaire. METHODS: We enrolled 319 children ages 0 to 16 years on ART in Kenya (n = 110), South Africa (n = 109) or Thailand (n = 100). Children were followed up for six months of adherence monitoring between March 2015 and August 2016 using Medication Event Monitoring Systems (MEMS® ) with at least one viral load measure. At month 3 and 6, children or their caregivers were administered a 10-item adherence questionnaire. Repeated measures analyses were used to compare responses on questionnaire items to external adherence criteria: MEMS® dichotomized adherence (≥90% of doses taken vs. <90%), 48-hour MEMS® treatment interruptions and viral suppression (<1000 copies/mL). Items associated with outcomes (p < 0.10) were coefficient-weighted to calculate a total adherence score, which was tested in multivariate regression against MEMS® and viral suppression outcomes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: Mean child age was 11 years and 54% were female. Children from Thailand (median age 14 years) were significantly older compared to Kenya (10 years) and South Africa (10 years). Prevalence of viral suppression was 97% in Thailand, 81% in South Africa and 69% in Kenya, while the prevalence of MEMS® adherence ≥90% was 57% in Thailand, 58% in South Africa and 40% in Kenya. Across sites, child-reported adherence using the questionnaire was significantly associated with dichotomized MEMS® adherence (OR 1.8, 95% CI 1.4 to 2.4), 48-hour treatment interruptions (OR 0.41, 95% CI 0.3 to 0.6), and viral suppression (OR 3.4, 95% CI 1.7 to 6.7). We did find, however, that different cut-points for the adherence score may be context-specific. For example, MEMS® non-adherent children in Kenya had a lower adherence score (0.98) compared to South Africa (1.77) or Thailand (1.58). CONCLUSIONS: We found suboptimal adherence to ART was common by multiple measures in this multi-country cohort of children. The short-form questionnaire demonstrated reasonable validity to screen for non-adherence in these diverse settings.

A systematic review of pediatric adherence to antiretroviral therapy in low- and middle-income countries.

BACKGROUND: Sustaining antiretroviral therapy (ART) adherence requires accurate, consistent monitoring, a particular challenge for low-income countries. The optimal strategy to measure pediatric adherence remains unclear. OBJECTIVE: To conduct a systematic review of pediatric ART adherence measurement techniques, adherence estimates, and clinical correlates in low- and middle-income countries to inform ART adherence monitoring. METHODS: We searched online bibliographic databases, including MEDLINE and EMBASE, using systematic criteria. Two reviewers selected all descriptive or interventional studies involving nonpregnant, HIV-positive individuals < or =18 years old that measured ART adherence in low- or middle-income countries as defined by World Bank criteria. Data were extracted regarding sample characteristics, study setting, measurement strategy, adherence estimate, and adherence correlates. RESULTS: The search yielded 1566 titles, of which 17 met selection criteria. Adherence measurement strategies included self- or proxy-report measures (14 studies), pill counts (4 studies), pharmacy records, drug levels, clinic adherence, and directly observed therapy (1 study each). The self- or proxy-report measures were heterogeneous, and few employed validation strategies. Caregiver-reported adherence was generally higher than self-report estimates. Pill counts revealed lower adherence estimates. Estimates of ART adherence ranged from 49% to 100%, with 76% of articles reporting >75% adherence. Factors related to family structure, socioeconomic status, disclosure, and medication regimen were all significantly associated with ART adherence. CONCLUSIONS: Pediatric HIV care programs in low- and middle-income countries use heterogeneous methods to measure ART adherence. Adherence estimates vary substantially, but most studies from low- and middle-income countries report >75% adherence, whereas most studies from high-income countries report <75% adherence.

The AMPATH medical record system: creating, implementing, and sustaining an electronic medical record system to support HIV/AIDS care in western Kenya.

Providing high-quality HIV/AIDS care requires high-quality, accessible data on individual patients and visits. These data can also drive strategic decision-making by health systems, national programs, and funding agencies. One major obstacle to HIV/AIDS care in developing countries is lack of electronic medical record systems (EMRs) to collect, manage, and report clinical data. In 2001, we implemented a simple primary care EMR at a rural health centre in western Kenya. This EMR evolved into a comprehensive, scalable system serving 19 urban and rural health centres. To date, the AMPATH Medical Record System contains 10 million observations from 400,000 visit records on 45,000 patients. Critical components include paper encounter forms for adults and children, technicians entering/managing data, and modules for patient registration, scheduling, encounters, clinical observations, setting user privileges, and a concept dictionary. Key outputs include patient summaries, care reminders, and reports for program management, operating ancillary services (e.g., tracing patients who fail to return for appointments), strategic planning (e.g., hiring health care providers and staff), reports to national AIDS programs and funding agencies, and research.

Pharmacokinetics-based adherence measures for antiretroviral therapy in HIV-infected Kenyan children.

BACKGROUND: Traditional medication adherence measures do not account for the pharmacokinetic (PK) properties of the drugs, potentially misrepresenting true therapeutic exposure. METHODS: In a population of HIV-infected Kenyan children on antiretroviral therapy including nevirapine (NVP), we used a one-compartment model with previously established PK parameters and Medication Event Monitoring Systems (MEMS®)-recorded dosing times to estimate the mean plasma concentration of NVP (Cp) in individual patients during 1 month of follow-up. Intended NVP concentration (Cp') was calculated under a perfectly followed dosing regimen and frequency. The ratio between the two (R = Cp/Cp') characterized the patient's NVP exposure as compared to intended level. Smaller R values indicated poorer adherence. We validated R by evaluating its association with MEMS®-defined adherence, CD4%, and spot-check NVP plasma concentrations assessed at 1 month. RESULTS: In data from 152 children (82 female), children were mean age 7.7 years (range 1.5-14.9) and on NVP an average of 2.2 years. Mean MEMS® adherence was 79%. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS® adherence (p < 0.0001), and lower-than-median R values were significantly associated with lower NVP drug concentrations (p = 0.0018) and lower CD4% (p = 0.0178), confirming a smaller R value showed poorer adherence. CONCLUSION: The proposed adherence measures, R, captured patient drug-taking behaviours and PK properties.

HIV Stigma: Perspectives from Kenyan Child Caregivers and Adolescents Living with HIV.

Stigma shapes all aspects of HIV prevention and treatment, yet there are limited data on how HIV-infected youth and their families are affected by stigma in sub-Saharan Africa. The authors conducted a qualitative study using focus group discussions among 39 HIV-infected adolescents receiving care at HIV clinics in western Kenya and 53 caregivers of HIV-infected children. Participants felt that while knowledge and access to treatment were increasing, many community members still held negative and inaccurate views about HIV, including associating it with immorality and believing in transmission by casual interactions. Stigma was closely related to a loss of social and economic support but also included internalized negative feelings about oneself. Participants identified treatment-related impacts of stigma, including nonadherence, nondisclosure of status to child or others, and increased mental health problems. Qualitative inquiry also provided insights into how to measure and reduce stigma among affected individuals and families.