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Long-term trends in mortality and AIDS-defining events among perinatally
HIV-infected children across Europe and Thailand
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There were 94 deaths and 174 first AIDS-defining events, of which 43(46%) and 79(45%) occurred within 6 months of cART initiation
Most common events were encephalopathy (n=38, 18%), TB (n=34, 16%) and wasting syndrome (n=31, 14%)
The raised mortality risk in those age≥14 and in middle-income countries raises concern.
A. Judd1, E. Chappell1, K. Doerholt2, L. Galli3, C. Giaquinto4, D. Gibb1, T. Goetghebuer5, S. Le Coeur6, A. Noguera Julian7, A. Turkova1, R. Goodall1, European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC)
Institutions
1University College London (UCL), MRC Clinical Trials Unit, London, United Kingdom, 2St George's Hospital NHS Trust, London, United Kingdom, 3University of Florence, Florence, Italy, 4PENTA Foundation, Padova, Italy, 5Hopital St Pierre, Brussels, Belgium, 6IRD 174 - PHPT, Chiang Mai, Thailand, 7Hospital Sant Joan de Deu Barcelona, Barcelona, Spain
Abstract
Background: There are limited data on the prognostic effects of time-updated covariates on long-term mortality rates of perinatally HIV-infected children after starting ART. We analysed individual patient data from 19 cohorts in 16 European countries and Thailand in EPPICC.
Methods: Perinatally HIV-infected children aged < 18yrs starting cART were followed until death, loss to follow-up (LTFU), transfer to adult care, their 21st birthday or last visit to 31/12/2013. Crude rates of death and first AIDS-defining events were calculated.
Baseline and time-updated risk factors for death ≤/>6 months of cART and progression to AIDS were assessed using inverse-probability-censoring-weighted Cox models to account for informative censoring of LTFU.
Results: Of 3527 children, 32%, 20%, 18% and 30% were from the UK/Ireland, Thailand, Russia/Ukraine, and the rest of Europe respectively. At cART initiation, median (IQR) age was 5.2(1.4-9.3) years and 42% had severe WHO immunological stage. Median follow-up was 5.6(2.9-8.7) years.
There were 94 deaths and 174 first AIDS-defining events, of which 43(46%) and 79(45%) occurred within 6 months of cART initiation. The crude mortality rate was 2.50[95%CI 1.86-3.38]/100 person-years (PY) in the ≤6 month period, and 0.27[0.21-0.36] thereafter. 59(63%) {31≤6 months} deaths were from HIV-related infections, 19(20%) {9} HIV-related non-infectious conditions, 12(13%) {1} HIV-unrelated, and 4(4%) {2} unknown. The rate of first AIDS-defining event was 0.88[0.76-1.02]/100PY, including 31(18%) HIV encephalopathy, 29(17%) tuberculosis and 25(14%) HIV wasting syndrome. The Table shows multivariable predictors of increased risk of death >6 months of cART. Predictors for death ≤6 months (baseline only) and progression to AIDS (baseline and time-updated) were broadly similar.
Conclusions: Almost half of deaths occurred ≤6 months of cART, after which current severe WHO immune stage, low BMI-for-age z-score, and fewer VL copy-years suppressed were the strongest predictors for mortality. The raised mortality risk in those age≥14 and in middle-income countries raises concern.
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