Immunodeficiency in Children Starting Antiretroviral Therapy in Low-, Middle-, and High-Income Countries

Abstract

Background The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) are important prognostic factors in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle- and high-income countries. Methods We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America and the United States of America (USA). Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country and calendar year. Results 34,706 children from nine low-income, six lower middle-income, four upper middle-income countries and one high-income country (United States of America, USA) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the USA, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. Conclusions Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

“…Before treatment, the ESC and the LSC both had a high proportion (47% vs. 56%) (p=0.56) of children with severe immunosuppression (<15% CD4 + %). This is consistent with a review from Koller et al who reported 70% of severe immunosuppression in children <2 years of age who started treatment in low and middle-income countries in 2010 [22]. Surprisingly, patients included in the present study had comparable mean CD4 + % independently of age at HAART initiation.…”

Living and dying to be counted: What we know about the epidemiology of the global adolescent HIV epidemic

“…Based on an updated review (produced by Lynne Mofenson and commissioned by UNAIDS, and detailed in Annex 2 of reference [21]), on the probability of HIV transmission during pregnancy, delivery and breastfeeding, the number of children estimated to have become HIV infected was revised downward for current and historical years. Based on multiregional analyses performed by the International Epidemiologic Database to Evaluate AIDS (IeDEA), improvements were also made to more accurately reflect at what age children initiate ART [23,24]. Rather than assuming that a constant proportion of children less than age 15 years initiate ART as they become eligible as done in previous models, the current model uses age‐specific assumptions of the proportion of children starting on ART [3,20].…”

An update on the HIV treatment cascade in children and adolescents

“…The Paediatric Research in Emergency Departments International Collaborative (PRE-DICT) trial showed no difference in AIDS-free survival in children >1 year; however, the median age of patients in the study was 6.4 years [35]. In lowerto middle-income countries, ART initiation in children still occurred at advanced stages of immunodeficiency, highlighting the need for improved ART access [36]. Despite evidence from the PREDICT trial, several countries in sub-Saharan Africa have recommended immediate initiation of ART irrespective of CD4 count or clinical stage, in the 5-10 year age group, because of barriers in maintaining patients in non-ART programs [36].…”