Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with HIV in Europe and Thailand: cohort study
Authors: Collins IJ; European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord
Published in: Clin Infect Dis. 2019; 28. pii: ciz253. doi: 10.1093/cid/ciz253. [Epub ahead of print]
Background In HIV-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children on suppressive ART.
Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children aged<18 years at ART initiation, with sustained viral suppression (VS) (≤400copies/mL) for ≥1 year were included. The prevalence of PIR (defined as WHO advanced/severe immunosuppression for age: CD4%<30% in children aged<12 months, CD4%<25% in 12-35 months, CD4%<20% in 36-59 months; CD4%<15%/CD4<350 cells/mm3 in ≥5-years) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of AIDS or death on suppressive ART were calculated by PIR status.
Results Of 2318 children included, median age was 6.4 [IQR, 2.1, 10.4] years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis-B coinfection and residing in Thailand (all p≤0.03). Rates of AIDS/death (95% CI) per 100,000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92), p<0.001.
Conclusions One in eight children in our cohort experienced PIR despite sustained viral suppression. While the overall rate of AIDS/death was low, children with PIR had four-fold increase in risk of event as compared to immune responders.