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Introduction: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) globalproject. Methods: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if Results: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from 7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts Conclusions: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood. Keywords: adolescent; CD4; cohort studies; growth; HIV; perinatally acquired Additional information may be found under the Supporting Information tab of this article., 1 | INTRODUCTION In 2019, an estimated 1.7 million adolescents aged 10-19 years were living with HIV worldwide, with 90% of them in sub-Saharan Africa, and 8% in Asia and [...]

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 x 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., Author(s): Andrew R. Deathe [sup.1] , Eren Oyungu [sup.2] , Samuel O. Ayaya [sup.2] [sup.3] , Ananda R. Ombitsa [sup.3] , Carole I. McAteer [sup.3] [sup.4] , Rachel C. Vreeman [...]

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-levelcontexts may be criticalto adolescent HIV outcomes, but have often been overlooked. We investigated family-levelfactors 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 [greater than or equal to]60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Transcripts were analysed through thematic analysis. A conceptualmodelfor family-leveldomains 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 socialsupport to facilitate care. Others did not feelequipped 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-leveldomains 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-levelfactors are integralto retention in care for ALHIV The conceptualmodeldeveloped in this study for family-levelinfluences 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. Keywords: adherence; adolescents; HIV care continuum; retention; stigma; structuraldrivers, 1 | INTRODUCTION There are an estimated 1.7 million adolescents living with HIV (ALHIV, ages 10-19) globally [1]. Despite globalscale-up of antiretroviral therapy (ART), ALHIV experience poorer outcomes in the [...]

Introduction"Treat All" - the treatment of all people with HIV, irrespective of disease stage or CD4 cell count - represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub-Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation.MethodsThe Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision-makers, and HIV community representatives in East, Central, Southern and West Africa.Results and discussionThe process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders - groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub-national estimates of the size of key populations and describe those who remain underserved along the HIV-care continuum; (2) characterize the timeliness of HIV care and short- and long-term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV-drug resistance and regimen switching; and (4) identify cost-effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV-care continuum, particularly among underserved populations.ConclusionsReflecting consensus among a broad group of experts, researchers, policy- and decision-makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.

Introduction: The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (leDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV ( Methods: We analysed (i) leDEA observational data from CHIV in routine care globally, and (ii) novel data from an leDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). Results: Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions: Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated leDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics. Keywords: antiretroviral therapy; HIV; mortality; tracing; trends; under-ascertainment, 1 | INTRODUCTION Accurate estimates of the number of children living with HIV (CHIV) are essential for programme planning and resource allocation [1,2]. Further, the number of deaths among CHIV [...]

ObjectiveTo 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.MethodsThis 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.ResultsIn 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]).ConclusionsSelf-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.

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 [greater than or equal to]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 socia 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. Keywords: child; adolescent; retention in care; patient dropouts; psychological trauma; mental health, 1 | INTRODUCTION There are 1.7 million adolescents living with HIV (ALHIV, ages 10 to 19) globally, including approximately 110,000 in Kenya [1]. ALHIV experience higher rates of care disengagement [...]

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 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 puberta development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH. Keywords: HIV; adolescent; growth; stunting; cohort studies; developing countries, 1 | INTRODUCTION Adolescence, defined by the World Health Organization (WHO) as between 10 and 19 years of age [1], is a critical transition period in life, accompanied by significant [...]

Keywords: HIV; paediatrics; children; adolescents; antiretroviral therapy; resistance, Forty years ago, the first adult HIV cases were published, with infant cases following within a year [1]. As a few of these then-babies approach their 40th birthdays, both their [...]

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[R]) 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[R] dichotomized adherence (>90% of doses taken vs. 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[R] 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[R] 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 vira 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[R] 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. Keywords: HIV/AIDS; children; adherence; Kenya; Thailand; South Africa, 1 | INTRODUCTION In 2017, there were an estimated 1.8 million children under the age of 15 living with HIV, with 180,000 children newly infected, only 52% on life-saving antiretroviral [...]

Introduction: With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy (ART) on neurodevelopment. Methods: We systematically searched OVID Medline, PsycINFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results: The search yielded 3027 unique titles. Of the 255 critically reviewed full-text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV-exposed uninfected children compared to HIV-unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinica studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions: While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV-exposed uninfected and HIV-unexposed uninfected children and using exposures consistent with current clinical care. Keywords: antiretroviral therapy; brain; cognition; highly active; HIV; laboratory animal science; maternal exposure, 1 | INTRODUCTION For the 1.4 million children born annually to mothers living with HIV, there are concerns that HIV or antiretroviral therapy (ART) exposure may negatively impact neurodevelopment, including [...]

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 Results: Of the 61,242 ALHIV from 270 clinics in 34 countries included in the analysis, 69% (n = 42,138) entered care Conclusions: Both mortality and LTFU were worse among those entering care at [greater than or equal to]15 years. ALHIV should be evaluated apart from younger children and adults to identify population-specific reasons for death and LTFU. Keywords: adolescents; mortality; lost to follow-up; retention; global; HIV, 1 | INTRODUCTION UNAIDS estimates that there were 1.0 million female and 770,000 male adolescents living with HIV in 2017 (aidsinfo.unaids. org). The adolescent age group (10 to 19 years) [...]

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. Keywords: disclosure; adolescents; low- and middle-income countries; vertical HIV infection; counselling; site assessment, 1 | INTRODUCTION Disclosure of HIV serostatus to perinatally HIV-infected children and adolescents is an important part of paediatric HIV care. HIV is a highly stigmatized disease requiring lifelong treatment, [...]

Adolescents living with HIV (ALWH) are particularly susceptible to disruptions in care, which may lead to poor HIV-related health outcomes. Here, we report the results of a longitudinal phone-based study investigating impacts of the COVID-19 pandemic on ALWH in New York City. Participants (N = 10, mean age 21.2 years, 50% female) demonstrated substantial COVID-19 knowledge and identified Instagram as their primary source of COVID-19 information. Nearly all participants reported loss of income, and 50% reported experiencing food insecurity as a result of the pandemic. These findings highlight existing vulnerabilities among ALWH that may threaten the continuum of care. [ABSTRACT FROM AUTHOR]

HIV stigma is associated with delayed HIV disclosure and worse clinical outcomes for adolescents living with HIV (ALWH). Teachers critically influence school environments, but are understudied in terms of HIV stigma. We implemented a school-level, cluster-randomized trial to assess the impact of a one-day multi-media training on the knowledge, attitudes and beliefs (K/A/B) of school teachers in western Kenya. Teachers' K/A/B were evaluated at baseline and six months. Additionally, we assessed stigma with ALWH enrolled in the included schools to explore the impact of the training. Teachers (N = 311) and ALWH (N = 19) were enrolled from 10 primary and 10 secondary schools. The intervention and control groups did not significantly differ in overall stigma score (mean 1.83 vs. 1.84; adjusted difference, 0.18 [95% CI, −0.082 to 0.045]) at six months; however, we found a trend towards improvement in overall stigma score and a significant difference in the community discrimination sub-scale among secondary school teachers (mean 3.02 vs. 3.19; adjusted difference, −0.166 [95% CI, −0.310 to −0.022]). ALWH reported few experiences of discrimination, but emphasized keeping their HIV status secret (84%). The teacher-training reduced secondary school teacher perceptions of community-level stigma, but did not impact individual attitudes or beliefs.. [ABSTRACT FROM AUTHOR]

Abstract Introduction: Mental health is a critical and neglected global health challenge for adolescents infected with HIV. The prevalence of mental and behavioural health issues among HIV-infected adolescents may not [...]

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[R])-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[R]-defined adherence, CD4%, and spotcheck 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[R] adherence was 79%. The mean value of R was 1.11 (SD 0.37). R was positively associated with MEMS[R] 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. Keywords: pharmacokinetics; adherence; electronic dose monitoring; Nevirapine; measurement validation; pediatrics, Introduction Adherence to antiretroviral therapy (ART) is an essential component of successful management of HIV/AIDS [1]. Studies have consistently shown strong associations between poor ART adherence and adverse clinical outcomes, [...]

: Introduction: Limited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration. Methods: Patient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework. Results: Of the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm[sup.3] in SSA to 828 cells/mm[sup.3] in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was Conclusions: Children switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children., Introduction In 2018, there were an estimated 1.7 million children living with HIV globally and 160,000 new paediatric infections [1]. With the recommendation for immediate antiretroviral therapy (ART) [2], substantial [...]

: Introduction: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under‐resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV‐positive adults in antiretroviral therapy (ART) programmes in low‐ and middle‐income countries (LMIC). Methods: We collected data from HIV‐positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub‐Saharan Africa, Asia‐Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. Results and Discussion: We analysed 2695 HIV‐positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/μL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. Conclusions: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB., Introduction In low‐ and middle‐income countries (LMIC), tuberculosis (TB) accounts for approximately 40% of HIV/AIDS‐related deaths among adults, and half of those TB cases are undiagnosed at the time of [...]