Dual analysis of loss to follow-up for perinatally HIV-infected adolescents receiving combination antiretroviral therapy in Asia

Background: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions. Setting: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries. Methods: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method. Results: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation = 5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria. Conclusions: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care

Use and outcomes of antiretroviral monotherapy and treatment interruption in adolescents with perinatal HIV infection in Asia

Purpose: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. Methods: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced >= 2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. Results: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to >= 2 combination ART regimens. Treatment interruption was associated with CD4 count = 1,000 copies/mL, ART adverse event, and commencing ART age >= 10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. Conclusions: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes

Early and late virologic failure after virologic suppression in HIV-infected Asian children and adolescents

Background: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving. Setting: An Asian cohort in 16 pediatric HIV services across 6 countries. Methods: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA >= 1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA >= 1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure. Results: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure. Conclusions: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required

Kaposi sarcoma risk in HIV-infected children and adolescents on combination antiretroviral therapy from sub-Saharan Africa, Europe, and Asia

BACKGROUND  The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS  We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. RESULTS  We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS  HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk

Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that &gt;80% of children aged &lt;5&nbsp;years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low-, middle- and high-income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease. Methods: We included children aged &lt;16&nbsp;years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia-Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines. Results: We included 52,153 children from fourteen low-, eight lower middle-, five upper middle- and five high-income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low-income), 67% to 64% (lower middle-income) and 61% to 43% (upper middle-income countries). In high-income countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at cART initiation after the WHO guidelines revisions in 2006 (low-, lower middle- and upper middle-income countries) and 2010 (all countries). Conclusions: By 2013, less than half of children initiating cART had severe immunodeficiency worldwide. WHO treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, &gt;40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to &lt;20% in high-income countries