Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration

Abstract

Introduction The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow‐up (LTFU). We therefore estimated all‐cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. Methods We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia‐Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data ( n = 221). Results Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person‐years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.

High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study

“…To the best of our knowledge, this is the first multicountry tracing study among CAYHIV considered LTFU. The high rates of unreported mortality are consistent with results from a systematic review, 4 and a multiregional tracing study, 16 although mortality in our study was lower than a Zambian tracing study in which 26% of children had died. 17 The children in the Zambian study were younger (0–15 years) compared with those in our study (0–24 years) and as reported, younger children have a higher risk of mortality compared with older children.…”

Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi‐country tracing study and linkage to a health information exchange

“…Although mortality was higher among CAYHIV reported as LTFU and traced compared with those retained [16, 17, 25–28], previous studies have reported even higher mortality estimates in those LTFU [1, 3, 29]. In rural Tanzania, 40% of adults living with HIV who were reported LTFU and traced, had died [27].…”

Mortality Among Children Aged <5 Years Living with HIV Who Are Receiving Antiretroviral Treatment — U.S. President’s Emergency Plan for AIDS Relief, 28 Supported Countries and Regions, October 2020–September 2022

“…Among approximately 18 million persons living with HIV receiving ART through PEPFAR during October 2020-September 2022, prevalences of reported death were higher among children aged <5 years than among persons in older age groups, consistent with previously published findings (3). The additional finding that interruptions in treatment were also more common among children aged <5 years living with HIV might suggest that mortality is disproportionately underreported in this age group, because patients with interruptions in treatment or who are lost to follow-up might have died (3).…”