CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

HIV Med. 2019 Aug;20(7):456-472. doi: 10.1111/hiv.12745. Epub 2019 May 16.

Abstract

Objectives: The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART).

Methods: Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression.

Results: In 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%.

Conclusions: After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.

Keywords: antiretroviral therapy; paediatric; treatment interruption.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Europe
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Infant
  • Male
  • Regression Analysis
  • Thailand
  • Treatment Outcome

Substances

  • Anti-HIV Agents