Short-Term Risk of HIV Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy

Abstract

Background Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population. Methods In a cohort of HIV-infected ART-naive and -ineligible Ugandan children >1 year old, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan–Meier survival analysis and multivariate Cox proportional-hazards modeling. Results Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by WHO-stage 3/4 event(n=22), death (n=3), or WHO-defined CD4 threshold for ART-initiation(n=12). Significant univariate predictors were CD4%(HR=2.0 per 10% decrease, p=0.005), HIV-RNA level(HR=2.4 per log10 increase, p=0.002), male gender (HR:2.0, p=0.04), age < 3 years (HR=3.7, p=0.001), CD4-activation [%CD4+CD38+HLADR+] (HR=1.6 per 10% increase, p=0.05) and CD8-activation [%CD8+CD38+HLADR+](HR=1.3 per 10% increase, p=0.05] (HR=1.3, p=0.5). In multivariate analysis, CD4%(HR=2.0, p=0.034), HIV-RNA level(HR=1.8, p=0.013) and age < 3 years (HR:3.0, p=0.008) were independently predictive. Children with HIV-RNA >105 copies/ml and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years). Conclusions Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART. Alternate strategies for monitoring or ART-initiation may be needed to improve outcomes.

Factors Determining Survival and Retention among HIV-Infected Children and Adolescents in a Community Home-Based Care and a Facility-Based Family-Centred Approach in Kampala, Uganda: A Cohort Study

“…As shown by the literature, significant clinical events do occur in HIV-infected children and adolescents even before meeting the previous guidelines [19, 20]. Our data therefore support the 2013 WHO consolidated guidelines recommending early ART initiation for children less than five years old regardless of CD4 cell count [41].…”

“…As an illustration, retention varied from 71% to 95% and 62% to 93% at 12 and 24 months, respectively, among children and adolescents in ART programmes in several countries of SSA [ 18 ]. A prior study in Uganda showed that even with frequent CD4 monitoring, HIV-infected children experienced significant clinical events while ineligible for ART according to the 2006 WHO guidelines [ 19 ]. Another study in Uganda showed that mortality was highest among HIV-infected children under two years [ 20 ].…”

Paediatric HIV care in sub‐Saharan Africa: clinical presentation and 2‐year outcomes stratified by age group

“…These 'longterm survivors' have particular needs that are usually not adequately met in resource-limited settings. Whilst they do not have the same mortality risk as younger children as shown by this study and others (Charlebois et al 2010;Fenner et al 2010), they face significant morbidities, including risk of poor physical and neurodevelopmental growth, poor sexual maturation and risk of chronic lung disease (Smith et al 2012). Furthermore, from a social perspective, this group of children has a higher likelihood of being orphaned and often struggles with challenges in their home life as well as at school, which has implications for their adherence to treatment (Williams et al 2006).…”

“…Whilst they do not have the same mortality risk as younger children as shown by this study and others (Charlebois et al . ; Fenner et al . ), they face significant morbidities, including risk of poor physical and neurodevelopmental growth, poor sexual maturation and risk of chronic lung disease (Smith et al .…”

They are likely to be there: using a family-centered index testing approach to identify children living with HIV in Kenya

“…2–4 A delay in antiretroviral therapy (ART) initiation also increases the risk of morbidity and mortality among children. 5–8…”