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

Abstract

The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). MethodsData 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. ResultsIn 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%. ConclusionsAfter 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.Parameters were estimated using multilevel asymptotic regression models. The intercept represents the CD4% at restart of ART, with b representing the difference in mean CD4% in patients with specific characteristics and the reference group. Similarly, the asymptote represents the longer term CD4% (up to 24 months after restart) and b represents longer term differences in mean CD4%. C is a rate parameter; negative values indicate a slower increase in CD4% and positive values indicate a faster increase. The intercept, asymptote and C constants represent the mean CD4% at restart and in the long term and the rate parameter for patients in the reference groups. Time to half the total CD4% recovery can be estimated as In(2)/c. CI, confidence interval; VL, viral load.

Evolution of CD4 T-Cell Count With Age in a Cohort of Young People Growing Up With Perinatally Acquired Human Immunodeficiency Virus

“…However, the reasons for this decline remain unclear, including how much is part of the natural decline in CD4 count seen after infancy in the general population [ 12 ]. Previous studies have predicted that children who start ART at an early age are likely to follow a trajectory of CD4 that is expected in the general population [ 13 , 14 ], and higher CD4 counts before/at ART initiation have been associated with higher long-term CD4 [ 13–16 ] and a better CD4 response after treatment interruptions [ 17 ].…”