Growth Anthropometrics as a Metric of Malnutrition Disparities Among Young Children Affected by HIV who are Orphaned Maternally, Paternally, or Totally in Western Kenya: A Retrospective Chart Review.

This retrospective study investigated growth outcomes of Kenyan children born to women living with HIV, comparing children who were orphaned maternally, paternally, and totally (both parents deceased) to those who were non-orphaned. We reviewed HIV clinic visits performed in Kenya from January 2011 to August 2016 in children 0 to 4 years of age. Malnutrition was assessed using stunting, underweight status, and wasting (z-scores of ≤-2). Descriptive statistics, Chi-square, t-tests, multivariable logistic regression, and ANCOVA models were performed. Of 15 027 total children in the study population, 3.5% (n = 520) were orphaned maternally, 8.1% (n = 1222) were orphaned paternally, and 2.2% (n = 336) were orphaned totally. Children who were orphans had higher rates of malnutrition compared to non-orphans (P < .001). Children who were orphaned maternally and totally had lower anthropometric mean scores, presented to clinic later, and were more likely to be living with HIV. Children who are orphaned maternally or totally should be targeted in interventional strategies.

Prevalence, incidence and chronicity of child abuse among orphaned, separated, and street-connected children and adolescents in western Kenya: What is the impact of care environment?

BACKGROUND: The effect of different types of care environment on orphaned and separated children and adolescents' (OSCA) experiences of abuse in sub-Saharan Africa is uncertain. OBJECTIVE: Our two primary objectives were 1) to compare recent child abuse (physical, emotional, and sexual) between OSCA living in institutional environments and those in family-based care; and 2) to understand how recent child abuse among street-connected children and youth compared to these other vulnerable youth populations. PARTICIPANTS AND SETTING: This project followed a cohort of OSCA in Uasin Gishu County, Kenya (2009-2019). This analysis includes 2393 participants aged 18 years and below, 1017 from institutional environments, 1227 from family-based care, and 95 street-connected participants. METHODS: The primary outcome of interest was recent abuse. Multiple logistic regression was used to estimate the odds of recent abuse at baseline, follow-up, and chronically for each abuse domain and adjusted odds ratios (AOR) between care environments, controlling for multiple factors. RESULTS: In total, 47 % of OSCA reported ever experiencing any kind of recent abuse at baseline and 54 % in follow-up. Compared to those in family-based care, street-connected participants had a much higher reported prevalence of all types of recent abuse at baseline (AOR: 5.01, 95 % CI: 2.89, 9.35), in follow-up (AOR: 5.22, 95 % CI: 2.41, 13.98), and over time (AOR: 3.44, 95 % CI: 1.93, 6.45). OSCA in institutional care were no more likely than those in family-based care of reporting any recent abuse at baseline (AOR: 0.85 95 % CI: 0.59-1.17) or incident abuse at follow-up (AOR: 0.91, 95 % CI: 0.61-1.47). CONCLUSION: OSCA, irrespective of care environment, reported high levels of recent physical, emotional, and sexual abuse. Street-connected participants had the highest prevalence of all kinds of abuse. OSCA living in institutional care did not experience more child abuse than those living in family-based care.

HIV-1 Treatment Failure, Drug Resistance, and Clinical Outcomes in Perinatally Infected Children and Adolescents Failing First-Line Antiretroviral Therapy in Western Kenya.

BACKGROUND: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART). SETTING: Academic Model Providing Access to Healthcare, western Kenya. METHODS: Participants were enrolled in 2010-2013 (timepoint 1) and a subsample re-enrolled after 4-7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables. RESULTS: The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3). CONCLUSION: Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.

Preventive Health Service Coverage Among Infants and Children at Six Maternal-Child Health Clinics in Western Kenya: A Cross-Sectional Assessment.

OBJECTIVES: Despite the substantial reduction of child mortality in recent decades, Kenya still strives to provide universal healthcare access and to meet other international benchmarks for child health. This study aimed to describe child health service coverage among children visiting six maternal and child health (MCH) clinics in western Kenya. METHODS: In a cross-sectional study of Kenyan children who are under the age of 5 years presenting to MCH clinics, child health records were reviewed to determine coverage of immunizations, growth monitoring, vitamin A supplementation, and deworming. Among 78 children and their caregivers, nearly 70% of children were fully vaccinated for their age. RESULTS: We found a significant disparity in full vaccination coverage by gender (p = 0.017), as males had 3.5 × higher odds of being fully vaccinated compared to females. Further, full vaccination coverage also varied across MCH clinic sites ranging from 43.8 to 92.9%. CONCLUSIONS FOR PRACTICE: Health service coverage for Kenyan children in this study is consistent with national and sub-national findings; however, our study found a significant gender equity gap in coverage at these six clinics that warrants further investigation to ensure that all children receive critical preventative services.

FIRST- LINE ANTIRETROVIRAL TREATMENT FAILURE IN EAST AFRICAN CHILDREN.

Objectives: To describe the incidence of antiretroviral treatment failure and associated factors in a pediatric clinical cohort within the East African International epidemiology Databases to Evaluate AIDS (EA-IeDEA) consortium. Design: A retrospective cohort study. Clinical treatment failure was defined as advancement in clinical WHO stage, or CDC class at least 24 weeks after initiation of treatment. Immunological failure was defined as developing or returning to the following age-related immunological thresholds after at least 24 weeks on treatment; CD4 count of <200 or CD4%<10% for children aged 2-5 years and CD4 count of < 100 for a child aged > 5years. Setting: The study utilized the electronic medical records of HIV-infected pediatric patients enrolled into the EA-IeDEA consortium clinics from January 2005 to August 2012. Results: A total of 5927 children were included in the analysis. The estimated cumulative incidence of clinical ART treatment failure at one year and four years post ART initiation was11.5% and 31% respectively, while that of immunological treatment failure was at 3% and 22.5% respectively. The main factors associated with clinical failure were advanced clinical stage at ART-initiation, year started ART and residing in a rural area. Factors associated with immunological failure were male gender and age of the child at ART-initiation. Only 6% of those identified as having clinical treatment failure were switched to second line treatment during the four years of follow-up. Conclusion: The probability of clinical and immunologic failure was relatively high and increased with time.

Growth of young HIV-infected and HIV-exposed children in western Kenya: A retrospective chart review.

INTRODUCTION: The objective of this study was to determine the growth patterns, rates of malnutrition, and factors associated with malnutrition in children born to HIV-infected mothers in western Kenya using data from an electronic medical record system. METHODS: This study was a retrospective chart review of HIV-infected (HIV+) and-exposed (HEU) children (<5 years) using data collected prospectively in the course of routine clinical care and stored in the electronic medical record system in western Kenya between January 2011 and August 2016. Demographics and anthropometrics were described, with Chi-square testing to compare proportions. Multiple variable logistic regression analysis was used to identify correlates of children being stunted, underweight, and wasted. We also examined growth curves, using a resampling method to compare the areas under the fitted growth curves to compare males/females and HIV+/HEU. RESULTS: Data from 15,428 children were analyzed. The children were 51.6% (n = 7,955) female, 5.2% (n = 809) orphans, 83.3% (n = 12,851) were HEU, and 16.7% (n = 2,577) were HIV+. For HIV+ children assessed at 24 months, 50.9% (n = 217) were stunted, 26.5% (n = 145) were underweight, and 13.6% (n = 58) were wasted, while 45.0% (n = 577) of HEU children were stunted, 14.8% (n = 255) were underweight, and 5.1% (n = 65) were wasted. When comparing mean z-scores, HIV+ children tended to have larger and earlier dips in z-scores compared to HIV-exposed children, with significant differences found between the two groups (p<0.001). Factors associated with an increased risk of malnutrition included being male, HIV+, and attending an urban clinic. Maternal antiretroviral treatment during pregnancy and mixed feeding at 3 months of age decreased the risk of malnutrition. CONCLUSIONS: HIV+ and HEU children differ in their anthropometrics, with HIV+ children having overall lower z-scores. Continued efforts to develop and implement sustainable and effective interventions for malnutrition are needed for children born to HIV+ mothers.

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration.

INTRODUCTION: Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). METHODS: We included data from sub-Saharan Africa, the Asia-Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height-for-age z-scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. RESULTS: Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ<-2 SD) at ART initiation. Males and females did not differ by age and stunting at ART initiation, CD4 count over time or retention in care. At 10 years of age, 34% of males were stunted versus 39% of females (p < 0.001). Females had better subsequent growth, resulting in a higher prevalence of stunting for males compared to females by age 15 (48% vs. 25%) and 18 years (31% vs. 15%). In linear mixed models, older age at ART initiation and low CD4 count were associated with poor growth over time (p < 0.001). Those stunted at 10 years of age or at ART initiation had the greatest growth improvement during adolescence. CONCLUSIONS: Prevalence of stunting is high among APH worldwide. Substantial sex-based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in pubertal development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH.

Validation of an HIV/AIDS Stigma Measure for Children Living with HIV and Their Families.

BACKGROUND: There are few validated tools to measure stigma, particularly among children living with HIV and their families. METHODS: This study was nested within a larger study that followed 240 child-caregiver dyads (children aged 10-15 years) at 8 clinics in western Kenya. The stigma instrument was administered to all child-caregiver dyads at 2 time points 6 months apart. The primary end point was to construct validity assessed by comparison to criterion constructs using generalized estimating equation models. RESULTS: Mean age of child participants was 12.3 years and 52% were female. Generally, caregivers reported experiencing higher levels of HIV stigma compared to their children. Children (9%) and caregivers (14%) reported that HIV stigma made them feel stressed, anxious, and depressed. Child and caregiver stigma items showed high construct validity by emotional and behavioral outcomes. CONCLUSIONS: The stigma instrument showed high validity when compared to emotional and behavioral outcomes.

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.

Mortality and losses to follow-up among adolescents living with HIV in the IeDEA global cohort collaboration.

INTRODUCTION: We assessed mortality and losses to follow-up (LTFU) during adolescence in routine care settings in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS: Cohorts in the Asia-Pacific, the Caribbean, Central, and South America, and sub-Saharan Africa (Central, East, Southern, West) contributed data, and included adolescents living with HIV (ALHIV) enrolled from January 2003 and aged 10 to 19 years (period of adolescence) while under care up to database closure (June 2016). Follow-up started at age 10 years or the first clinic visit, whichever was later. Entering care at <15 years was a proxy for perinatal infection, while entering care ≥15 years represented infection acquired during adolescence. Competing risk regression was used to assess associations with death and LTFU among those ever receiving triple-drug antiretroviral therapy (triple-ART). RESULTS: Of the 61,242 ALHIV from 270 clinics in 34 countries included in the analysis, 69% (n = 42,138) entered care <15 years of age (53% female), and 31% (n = 19,104) entered care ≥15 years (81% female). During adolescence, 3.9% died, 30% were LTFU and 8.1% were transferred. For those with infection acquired perinatally versus during adolescence, the four-year cumulative incidences of mortality were 3.9% versus 5.4% and of LTFU were 26% versus 69% respectively (both p < 0.001). Overall, there were higher hazards of death for females (adjusted sub-hazard ratio (asHR) 1.19, 95% confidence interval (CI) 1.07 to 1.33), and those starting treatment at ≥5 years of age (highest asHR for age ≥15: 8.72, 95% CI 5.85 to 13.02), and in care in mostly urban (asHR 1.40, 95% CI 1.13 to 1.75) and mostly rural settings (asHR 1.39, 95% CI 1.03 to 1.87) compared to urban settings. Overall, higher hazards of LTFU were observed among females (asHR 1.12, 95% CI 1.07 to 1.17), and those starting treatment at age ≥5 years (highest asHR for age ≥15: 11.11, 95% CI 9.86 to 12.53), in care at district hospitals (asHR 1.27, 95% CI 1.18 to 1.37) or in rural settings (asHR 1.21, 95% CI 1.13 to 1.29), and starting triple-ART after 2006 (highest asHR for 2011 to 2016 1.84, 95% CI 1.71 to 1.99). CONCLUSIONS: Both mortality and LTFU were worse among those entering care at ≥15 years. ALHIV should be evaluated apart from younger children and adults to identify population-specific reasons for death and LTFU.

Early Childhood Development in Children Born to HIV-Infected Mothers: Perspectives From Kenyan Clinical Providers and Caregivers.

Objective. To understand the perspectives of clinical providers and caregivers regarding early childhood development (ECD) in children born to HIV-infected mothers in Kenya. Methods. This was a qualitative study of provider and caregiver perspectives on ECD at 5 Kenyan HIV clinics, using semistructured interviews and focus group discussions. Constant comparison and triangulation methods were employed to elucidate the concepts of ECD. Results. Twenty-five providers and 67 caregivers participated. While providers understood ECD in terms of milestones, caregivers strongly equated ECD with physical growth. Factors affecting ECD, such as nutrition, perinatal effects, and illness, were perceived differently by providers and caregivers. Both groups generally believed that HIV-infected children would have typical ECD if adherent to their HIV treatment. Conclusions. Important considerations regarding ECD in this population were uncovered. Understanding provider and caregiver perspectives' on ECD in HIV-exposed children is critical for promoting ECD in this community.

Adolescent pregnancy at antiretroviral therapy (ART) initiation: a critical barrier to retention on ART.

INTRODUCTION: Adolescence and pregnancy are potential risk factors for loss to follow-up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site-level factors on LTFU. METHODS: We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site-level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups. RESULTS: A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site-level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary-care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67). CONCLUSIONS: Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.

Models of support for disclosure of HIV status to HIV-infected children and adolescents in resource-limited settings.

INTRODUCTION: Disclosure of HIV status to HIV-infected children and adolescents is a major care challenge. We describe current site characteristics related to disclosure of HIV status in resource-limited paediatric HIV care settings within the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS: An online site assessment survey was conducted across the paediatric HIV care sites within six global regions of IeDEA. A standardized questionnaire was administered to the sites through the REDCap platform. RESULTS: From June 2014 to March 2015, all 180 sites of the IeDEA consortium in 31 countries completed the online survey: 57% were urban, 43% were health centres and 86% were integrated clinics (serving both adults and children). Almost all the sites (98%) reported offering disclosure counselling services. Disclosure counselling was most often provided by counsellors (87% of sites), but also by nurses (77%), physicians (74%), social workers (68%), or other clinicians (65%). It was offered to both caregivers and children in 92% of 177 sites with disclosure counselling. Disclosure resources and procedures varied across geographical regions. Most sites in each region reported performing staff members' training on disclosure (72% to 96% of sites per region), routinely collecting HIV disclosure status (50% to 91%) and involving caregivers in the disclosure process (71% to 100%). A disclosure protocol was available in 14% to 71% of sites. Among the 143 sites (79%) routinely collecting disclosure status process, the main collection method was by asking the caregiver or child (85%) about the child's knowledge of his/her HIV status. Frequency of disclosure status assessment was every three months in 63% of the sites, and 71% stored disclosure status data electronically. CONCLUSION: The majority of the sites reported offering disclosure counselling services, but educational and social support resources and capacities for data collection varied across regions. Paediatric HIV care sites worldwide still need specific staff members' training on disclosure, development and implementation of guidelines for HIV disclosure, and standardized data collection on this key issue to ensure the long-term health and wellbeing of HIV-infected youth.

Trends Over Time for Adolescents Enrolling in HIV Care in Kenya, Tanzania, and Uganda From 2001-2014.

BACKGROUND: The data needed to understand the characteristics and outcomes, over time, of adolescents enrolling in HIV care in East Africa are limited. SETTING: Six HIV care programs in Kenya, Tanzania, and Uganda. METHODS: This retrospective cohort study included individuals enrolling in HIV care as younger adolescents (10-14 years) and older adolescents (15-19 years) from 2001-2014. Descriptive statistics were used to compare groups at enrollment and antiretroviral therapy (ART) initiation over time. The proportion of adolescents was compared with the total number of individuals aged 10 years and older enrolling over time. Competing-risk analysis was used to estimate 12-month attrition after enrollment/pre-ART initiation; post-ART attrition was estimated by Kaplan-Meier method. RESULTS: A total of 6344 adolescents enrolled between 2001 and 2014. The proportion of adolescents enrolling among all individuals increased from 2.5% (2001-2004) to 3.9% (2013-2014, P < 0.0001). At enrollment, median CD4 counts in 2001-2004 compared with 2013-2014 increased for younger (188 vs. 379 cells/mm, P < 0.0001) and older (225 vs. 427 cells/mm, P < 0.0001) adolescents. At ART initiation, CD4 counts increased for younger (140 vs. 233 cells/mm, P < 0.0001) and older (64 vs. 323 cells/mm, P < 0.0001) adolescents. Twelve-month attrition also increased for all adolescents both after enrollment/pre-ART initiation (4.7% vs. 12.0%, P < 0.001) and post-ART initiation (18.7% vs. 31.2%, P < 0.001). CONCLUSIONS: Expanding HIV services and ART coverage was likely associated with earlier adolescent enrollment and ART initiation but also with higher attrition rates before and after ART initiation. Interventions are needed to promote retention in care among adolescents.

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort.

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years.

Adherence to antiretroviral therapy in a clinical cohort of HIV-infected children in East Africa.

OBJECTIVE: To describe antiretroviral therapy (ART) adherence and associated factors for a large HIV-infected pediatric cohort followed by sites of the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium. METHODS: This study utilized prospectively collected clinical data from HIV-infected children less than 13 years of age who initiated ART within 4 clinical care programs (with 26 clinical sites) in Kenya, Uganda, and Tanzania and were followed for up to 6 years. Programs used one of 3 adherence measures, including 7-day quantitative recall, 7-day categorical recall, and clinician pill assessments. We fit a hierarchical, three-level, logistic-regression model to examine adherence, with observations nested within patient, and patients within the 26 sites providing pediatric HIV data to this analysis. RESULTS: In East Africa, 3,304 children, 52.0% male, were enrolled in care and were subsequently observed for a median of 92 weeks (inter-quartile range [IQR] 50.3-145.0 weeks). Median age at ART initiation was 5.5 years ([IQR] 3.0-8.5 years). "Good" adherence, as reported by each clinic's measures, was extremely high, remaining on average above 90% throughout all years of follow-up. Longer time on ART was associated with higher adherence (adjusted Odds Ratio-aOR-per log-transformed week on ART: 1.095, 95% Confidence Interval-CI-[1.052-1.150].) Patients enrolled in higher-volume programs exhibited higher rates of clinician-assessed adherence (aOR per log-500 patients: 1.174, 95% CI [1.108-1.245]). Significant site-level variability in reported adherence was observed (0.28), with even higher variability among patients (0.71). In a sub-analysis, being an orphan at the start of ART was strongly associated with lower ART adherence rates (aOR: 0.919, 95% CI [0.864-0.976]). CONCLUSIONS: Self-reported adherence remained high over a median of 1.8 years in HIV care, but varied according to patient-level and site-level factors. Consistent adherence monitoring with validated measures and attention to vulnerable groups is recommended.

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.

Transition from paediatric to adult care of adolescents living with HIV in sub-Saharan Africa: challenges, youth-friendly models, and outcomes.

INTRODUCTION: The number of adolescents with perinatally or behaviourally acquired HIV is increasing in low-income countries, and especially in sub-Saharan Africa where HIV prevalence and incidence are the highest. As they survive into adulthood in the era of antiretroviral therapy, there is a pressing need to transfer them from paediatric to adult care, known as the transition of care. We conducted a narrative review of recent evidence on their transition outcomes in Africa, highlighting the specific needs and challenges in these populations and settings, and the different models of care for transition. AREAS COVERED: We searched PubMed bibliographic database, HIV conference content, and grey literature from January 2000 to August 2016 with the following keywords: HIV infections AND (adolescents or youth) AND transition AND Africa. All qualitative and quantitative, experimental and observational studies including HIV-infected patients aged 10-24 years with information on transition were eligible. RESULTS: Few data on transition outcomes for HIV-infected adolescents are available from Africa settings. Studies mainly from Southern and East Africa reported on the barriers to successful transition, highlighting several gaps. These included lack of adequate infrastructure, staff training and communication between paediatric and adult clinicians as well as the fear of stigma of adolescents and youth living with HIV. Most countries have no specific national guidelines on when to disclose HIV status or when and how to transition to adult care. Several models of care adapted to the adolescent transition question have been implemented in specific settings. These models include teen clinics, peer educators or the use of social media. However, regardless of the model, services are increasingly overburdened and have insufficient human resources. Furthermore, very high attrition has been observed among adolescents and youth compared to younger children or older adults. There is a need to identify sub-groups at higher risk of loss to follow-up for targeted care and peer support. EXPERT COMMENTARY: Although the available HIV-related data on adolescent transition outcomes are limited, there is evidence of their increased vulnerability during this period. Standardized data gathering, analysis, and reporting systems specific to adolescent transition are essential to improve understanding and adolescent outcomes in Africa.

Sexual Behavior Among Orphaned Adolescents in Western Kenya: A Comparison of Institutional- and Family-Based Care Settings.

PURPOSE: This study sought to assess whether risky sexual behaviors and sexual exploitation of orphaned adolescents differed between family-based and institutional care environments in Uasin Gishu County, Kenya. METHODS: We analyzed baseline data from a cohort of orphaned adolescents aged 10-18 years living in 300 randomly selected households and 19 charitable children's institutions. The primary outcomes were having ever had consensual sex, number of sex partners, transactional sex, and forced sex. Multivariate logistic regression compared these between participants in institutional care and family-based care while adjusting for age, sex, orphan status, importance of religion, caregiver support and supervision, school attendance, and alcohol and drug use. RESULTS: This analysis included 1,365 participants aged ≥10 years: 712 (52%) living in institutional environments and 653 (48%) in family-based care. Participants in institutional care were significantly less likely to report engaging in transactional sex (adjusted odds ratio, .46; 95% confidence interval, .3-.72) or to have experienced forced sex (adjusted odds ratio, .57; 95% confidence interval, .38-.88) when controlling for age, sex, and orphan status. These associations remained when adjusting for additional variables. CONCLUSIONS: Orphaned adolescents living in family-based care in Uasin Gishu, Kenya, may be at increased risk of transactional sex and sexual violence compared to those in institutional care. Institutional care may reduce vulnerabilities through the provision of basic material needs and adequate standards of living that influence adolescents' sexual risk-taking behaviors. The use of single items to assess outcomes and nonexplicit definition of sex suggest the findings should be interpreted with caution.

Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds.