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

Abstract

IntroductionThe 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 >80% of children aged <5 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.MethodsWe included children aged <16 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.ResultsWe 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).ConclusionsBy 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, >40% of children in low‐ and middle‐income countries started cART with severe immunodeficiency compared to <20% in high‐income countries.

Effectiveness of symptom-based diagnostic HIV testing versus targeted and blanket provider-initiated testing and counseling among children and adolescents in Cameroon

“…The better ART linkage rates could be the results of the longer exposure to the “test and treat” policy in these 2 health facilities. This is an indication of the positive impact of policy change for early ART initiation as evidenced by previous studies [29,30].…”

CD4 Trends With Evolving Treatment Initiation Policies Among Children Living With HIV in Zambézia Province, Mozambique, 2012–2018

“…Regardless, it is notable that we observed a decrease in severe immunodeficiency at ART initiation from 33% in 2013 to 15% in 2018. Similar LMIC cohorts reported 58%–66% of children starting ART with severe immunodeficiency in 2010, 22 and 42%–64% in 2013 21 ; however, inclusion of children younger than 5 years in these cohorts limits comparability.…”

“…By contrast, it is expected that HIV-related immunodeficiency should be less severe among CLHIV initiating ART in the Test and Start era, wherein universal and immediate treatment is recommended, regardless of immunologic or clinical status. However, previous studies of HIV-related immunodeficiency among children relative to ART program maturation included only children starting ART before 2013, 21,22 and more recent studies focused solely on adults, 23,24 so less is known about CLHIV receiving HIV care and treatment in Mozambique in recent years. Therefore, the objectives of this evaluation were to describe the degree of immunodeficiency and to identify risk factors for enrolling in HIV care and starting ART with severe immunodeficiency among children during the period of evolving ART initiation policies in Zambézia Province, Mozambique.…”

Cohort profile: The International epidemiology Databases to Evaluate AIDS (IeDEA) in sub-Saharan Africa, 2012-2019

“…The African regions of IeDEA have collaborated and continue to encourage collaborations with other consortia, cohort collaborations, the HIV modelling community and public health agencies as well as individuals wishing to use IeDEA data. Examples include work with COHERE [50,58,67,68], the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) collaboration [36,69] or the Measurement & Surveillance of HIV Epidemics (MeSH) consortium [22] as well as UNAIDS [22,23] and WHO [21]. Furher collaborations are welcome.…”