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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 [...], 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. more...

1 | INTRODUCTION Access to and uptake of antiretroviral therapy (ART) have improved the health of pregnant women living with HIV (WLHIV) and decreased new paediatric HIV infections [1-3], but [...], Introduction: Young pregnant and postpartum women living with HIV (WLHIV) are at high risk of poor outcomes in prevention of mother-to-child transmission services. The aim of this systematic review was to collate evidence on strategies to improve retention in antenatal and/or postpartum care in this population. We also conducted a secondary review of strategies to increase attendance at antenatal care (ANC) and/or facility delivery among pregnant adolescents, regardless of HIV status, to identify approaches that could be adapted for adolescents and young WLHIV. Methods: Selected databases were searched on 1 December 2020, for studies published between January 2006 and November 2020, with screening and data abstraction by two independent reviewers. We identified papers that reported age-disaggregated results for adolescents and young WLHIV aged Results and discussion: Of 37 papers examining approaches to increase retention among pregnant and postpartum WLHIV, only two reported age-disaggregated results: one showed that integrated care during the postpartum period increased retention in HIV care among women aged 18 to 24 years; and another showed that a lay counsellor-led combination intervention did not reduce attrition among women aged 16 to 24 years; one further study noted that age did not modify the effectiveness of a combination intervention. Mobile health technologies, enhanced support, active follow-up and tracing and integrated services were commonly examined as standalone interventions or as part of combination approaches, with mixed evidence for each strategy. Of 10 papers identified in the secondary search, adolescent-focused services and continuity of care with the same provider appeared to be effective in improving attendance at ANC and/or facility delivery, while home visits and group ANC had mixed results. Conclusions: This review highlights the lack of evidence regarding effective strategies to improve retention in antenatal and/or postpartum care among adolescents and young WLHIV specifically, as well as a distinct lack of age-disaggregated results in studies examining retention interventions for pregnant WLHIV of all ages. Identifying and prioritizing approaches to improve retention of adolescents and young WLHIV are critical for improving maternal and child health. Keywords: prevention of mother-to-child transmission; adolescents living with HIV; retention; adolescent pregnancy; antenata care; HIV cascade more...

1 | INTRODUCTION Sustained engagement in antiretroviral therapy (ART) services during and after pregnancy is critical for the prevention of mother-to-child transmission (PMTCT) of HIV and to optimize maternal health. [...], Introduction: Women living with HIV are required to transition into the prevention of mother-to-child transmission of HIV (PMTCT) services when they become pregnant and back to ART services after delivery. Transition can be a vulnerable time when many women are lost from HIV care yet there is little guidance on the optimal transition approaches to ensure continuity of care. We reviewed the available evidence on existing approaches to transitioning women into and out of PMTCT, outcomes following transition and factors influencing successful transition. Methods: We searched PubMed and SCOPUS, as well as abstracts from international HIV-focused meetings, from January 2006 to July 2020. Studies were included that examined three points of transition: pregnant women already on ART into PMTCT (transition 1), pregnant women living with HIV not yet on ART into treatment services (transition 2) and postpartum women from PMTCT into general ART services after delivery (transition 3). Results were grouped and reported as descriptions of transition approach, comparison of outcomes following transition and factors influencing successful transition. Results & discussion: Out of 1809 abstracts located, 36 studies (39 papers) were included in this review. Three studies included transition 1, 26 transition 2 and 17 transition 3. Approaches to transition were described in 26 studies and could be grouped into the provision of information at the point of transition (n = 8), strengthened communication or linkage of data between services (n = 4), use of transition navigators (n = 12), and combination approaches (n = 4). Few studies were designed to directly assess transition and only nine compared outcomes between transition approaches, with substantia heterogeneity in study design, setting and outcomes. Four themes were identified in 25 studies reporting on factors influencing successful transition: fear, knowledge and preparedness, clinic characteristics and the transition requirements and process. Conclusions: This review highlights that, despite the need for women to transition into and out of PMTCT services for continued ART in many settings, there is very limited evidence on optimal transition approaches. Ongoing operational research is required to identify sustainable and acceptable transition approaches and service delivery models that support continuity of HIV care during and after pregnancy. Keywords: transition; transfer; prevention of mother-to-child transmission; linkage; continuity of care; antiretroviral therapy more...

1 | INTRODUCTION In 2015, World Health Organization (WHO) guidelines recommended treatment for all persons living with HIV (PLHIV) [1] in order to maximize the benefits of treatment for individuals [...], Introduction: Despite increasing focus on test and treat strategies for people living with HIV (PLHIV), many continue to enrol late in care and initiate antiretroviral therapy (ART) when they have advanced HIV disease. Methods: We analyzed PLHIV [greater than or equal to]15 years of age starting ART in Ethiopia, Kenya, Mozambique and Tanzania from 2005 to 2015 based on CD4+ groups at ART initiation ([greater than or equal to]200, 100 to 199, 50 to 99 and 6 months; deaths were ascertained from medical records. Results and discussion: A total of 305,443 PLHIV were included in the analysis: 118,580 (38.8%) CD4+ [greater than or equal to]200, 91,788 (30.1%) CD4+ 100 to 199, 44,029 (14.4%) CD4+ 50 to 99 and 51,046 (16.7%) CD4+ Conclusions: Greater efforts, including the identification of effective differentiated service delivery models, are needed to ensure that all PLHIV starting treatment can garner the benefits from ART and achieve favourable outcomes. Keywords: CD4 cell count; late ART initiation; loss to follow-up; mortality; attrition; differentiated service delivery models more...

1 | INTRODUCTION Access to early testing for HIV-exposed infants and to antiretroviral therapy (ART) for children living with HIV has expanded globally; however, significant gaps exist across the testing [...], Introduction: There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low-resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa. Methods: The Pediatric Enhanced Surveillance Study enrolled HIV-infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result 30 days after the VS date. Results: Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age 1 million copies/mL at ART initiation were half as likely to achieve VS 1000 copies/mL. Children 1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds. Conclusions: We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes. Keywords: viral load; viral load suppression; paediatric HIV; antiretroviral therapy; viral load rebound; late ART initiation more...

Introduction Access to and uptake of antiretroviral therapy (ART) have improved the health of pregnant women living with HIV (WLHIV) and decreased new paediatric HIV infections [1?3], but retaining women [...], : Introduction: Young pregnant and postpartum women living with HIV (WLHIV) are at high risk of poor outcomes in prevention of mother?to?child transmission services. The aim of this systematic review was to collate evidence on strategies to improve retention in antenatal and/or postpartum care in this population. We also conducted a secondary review of strategies to increase attendance at antenatal care (ANC) and/or facility delivery among pregnant adolescents, regardless of HIV status, to identify approaches that could be adapted for adolescents and young WLHIV. Methods: Selected databases were searched on 1 December 2020, for studies published between January 2006 and November 2020, with screening and data abstraction by two independent reviewers. We identified papers that reported age?disaggregated results for adolescents and young WLHIV aged Results and discussion: Of 37 papers examining approaches to increase retention among pregnant and postpartum WLHIV, only two reported age?disaggregated results: one showed that integrated care during the postpartum period increased retention in HIV care among women aged 18 to 24 years; and another showed that a lay counsellor?led combination intervention did not reduce attrition among women aged 16 to 24 years; one further study noted that age did not modify the effectiveness of a combination intervention. Mobile health technologies, enhanced support, active follow?up and tracing and integrated services were commonly examined as standalone interventions or as part of combination approaches, with mixed evidence for each strategy. Of 10 papers identified in the secondary search, adolescent?focused services and continuity of care with the same provider appeared to be effective in improving attendance at ANC and/or facility delivery, while home visits and group ANC had mixed results. Conclusions: This review highlights the lack of evidence regarding effective strategies to improve retention in antenatal and/or postpartum care among adolescents and young WLHIV specifically, as well as a distinct lack of age?disaggregated results in studies examining retention interventions for pregnant WLHIV of all ages. Identifying and prioritizing approaches to improve retention of adolescents and young WLHIV are critical for improving maternal and child health. more...

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 [...] more...

Introduction UNAIDS estimated that as of 2015, 1.8 million children Scale up of HIV treatment in rural areas and decentralization of paediatric care to lower-level health facilities have been critical [...], Introduction: Decentralization of HIV care for children has been recommended to improve paediatric outcomes by making antiretroviral treatment (ART) more accessible. We documented outcomes of children transferred after initiating ART at a large tertiary hospital in the Eastern Cape of South Africa. Methods: Electronic medical records for all children 0-15 years initiating ART at Dora Nginza Hospital (DNH) in Port Elizabeth, South Africa January 2004 to September 2015 were examined. Records for children transferred to primary and community clinics were searched at 16 health facilities to identify children with successful (at least one recorded visit) and unsuccessful transfer (no visits). We identified all children lost to follow-up (LTF) after ART initiation: those LTF at DNH (no visit >6 months), children with unsuccessful transfer, and children LTF after successful transfer (no visit >6 months). Community tracing was conducted to locate caregivers of children LTF and electronic laboratory data were searched to measure reengagement in care, including silent transfers. Results: 1,582 children initiated ART at median age of 4 years [interquartile range (IQR): 1-8] and median CD4+ of 278 cells/m[m.sup.3] [IQR: 119-526]. A total of 901 (57.0%) children were transferred, 644 (71.5%) to study facilities; 433 (67.2%) children had successful transfer and 211 (32.8%) had unsuccessful transfer. In total, 399 children were LTF: 105 (26.3%) from DNH, 211 (52.9%) through unsuccessful transfer and 83 (20.8%) following successful transfer. Community tracing was conducted for 120 (30.1%) of 399 children LTF and 66 (55.0%) caregivers were located and interviewed. Four children had died. Among 62 children still alive, 8 (12.9%) were reported to not be in care or taking ART and 18 (29.0%) were also not taking ART. Overall, 65 (16.3%) of 399 children LTF had a laboratory result within 18 months of their last visit indicating silent transfer and 112 (28.1%) had lab results from 2015 to 2016 indicating current care. Conclusion: We found that only two-thirds of children on ART transferred to primary and community health clinics had successful transfer. These findings suggest that transfer is a particularly vulnerable step in the paediatric HIV care cascade. Keywords: loss to follow-up; paediatric HIV; ART; decentralization; referral; retention more...

INTRODUCTION Sustained engagement in antiretroviral therapy (ART) services during and after pregnancy is critical for the prevention of mother?to?child transmission (PMTCT) of HIV and to optimize maternal health. High rates [...], : Introduction: Women living with HIV are required to transition into the prevention of mother?to?child transmission of HIV (PMTCT) services when they become pregnant and back to ART services after delivery. Transition can be a vulnerable time when many women are lost from HIV care yet there is little guidance on the optimal transition approaches to ensure continuity of care. We reviewed the available evidence on existing approaches to transitioning women into and out of PMTCT, outcomes following transition and factors influencing successful transition. Methods: We searched PubMed and SCOPUS, as well as abstracts from international HIV?focused meetings, from January 2006 to July 2020. Studies were included that examined three points of transition: pregnant women already on ART into PMTCT (transition 1), pregnant women living with HIV not yet on ART into treatment services (transition 2) and postpartum women from PMTCT into general ART services after delivery (transition 3). Results were grouped and reported as descriptions of transition approach, comparison of outcomes following transition and factors influencing successful transition. Results & discussion: Out of 1809 abstracts located, 36 studies (39 papers) were included in this review. Three studies included transition 1, 26 transition 2 and 17 transition 3. Approaches to transition were described in 26 studies and could be grouped into the provision of information at the point of transition (n = 8), strengthened communication or linkage of data between services (n = 4), use of transition navigators (n = 12), and combination approaches (n = 4). Few studies were designed to directly assess transition and only nine compared outcomes between transition approaches, with substantial heterogeneity in study design, setting and outcomes. Four themes were identified in 25 studies reporting on factors influencing successful transition: fear, knowledge and preparedness, clinic characteristics and the transition requirements and process. Conclusions: This review highlights that, despite the need for women to transition into and out of PMTCT services for continued ART in many settings, there is very limited evidence on optimal transition approaches. Ongoing operational research is required to identify sustainable and acceptable transition approaches and service delivery models that support continuity of HIV care during and after pregnancy. more...

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: 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. more...

Introduction In 2015, World Health Organization (WHO) guidelines recommended treatment for all persons living with HIV (PLHIV) in order to maximize the benefits of treatment for individuals with HIV and [...], : Introduction: Despite increasing focus on test and treat strategies for people living with HIV (PLHIV), many continue to enrol late in care and initiate antiretroviral therapy (ART) when they have advanced HIV disease. Methods: We analyzed PLHIV ?15 years of age starting ART in Ethiopia, Kenya, Mozambique and Tanzania from 2005 to 2015 based on CD4+ groups at ART initiation (?200, 100 to 199, 50 to 99 and 6 months; deaths were ascertained from medical records. Results and discussion: A total of 305,443 PLHIV were included in the analysis: 118,580 (38.8%) CD4+ ?200, 91,788 (30.1%) CD4+ 100 to 199, 44,029 (14.4%) CD4+ 50 to 99 and 51,046 (16.7%) CD4+ Conclusions: Greater efforts, including the identification of effective differentiated service delivery models, are needed to ensure that all PLHIV starting treatment can garner the benefits from ART and achieve favourable outcomes. more...

Introduction Access to early testing for HIV?exposed infants and to antiretroviral therapy (ART) for children living with HIV has expanded globally; however, significant gaps exist across the testing to treatment [...], : Introduction: There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low?resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa. Methods: The Pediatric Enhanced Surveillance Study enrolled HIV?infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result 30 days after the VS date. Results: Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age 1 million copies/mL at ART initiation were half as likely to achieve VS 1000 copies/mL. Children 1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds. Conclusions: We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes. more...

Author(s): The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, Amy L. Slogrove 1, Michael Schomaker 1, Mary-Ann Davies 1, Paige Williams 2, Suna Balkan 3, [...], Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses. more...