Incomplete immune reconstitution despite virologic suppression in HIV-1 infected children and adolescents

Objectives: Some perinatally infected children do not regain normal CD4⁺ T-cell counts despite suppression of HIV-1 plasma viremia by antiretroviral therapy (ART). The frequency, severity and significance of these discordant treatment responses remain unclear. Design: We examined the persistence of CD4⁺ lymphocytopenia despite virologic suppression in 933 children (-5 years of age) in the USA, Latin America and the Caribbean. Methods: CD4⁺ T-cell trajectories were examined and Kaplan-Meier methods used to estimate median time to CD4⁺ T-cell count at least 500 cells/ml. Results: After 1 year of virologic suppression, most (99%) children achieved a CD4⁺ T-cell count of at least 200 cells/ml, but CD4⁺ T-cell counts remained below 500 cells/ml after 1 and 2 years of virologic suppression in 14 and8%of children, respectively.Median times to first CD4⁺ T-cell count at least 500 cells/ml were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/ml at the start of virologic suppression. New AIDS-defining events occurred in nine children, including four in the first 6 months of virologic suppression. Other infectious and HIV-related diagnoses occurred more frequently and across a wide range of CD4⁺ cell counts. Conclusion: ART improved CD4⁺ cell counts in most children, but the time to CD4⁺ cell count of at least 500 cells was highly dependent upon baseline immunological status. Some children did not reach a CD4⁺ T-cell count of 500cells/ml despite 2 years of virologic suppression. AIDS-defining events occurred in 1% of the population, including children in whom virologic suppression and improved CD4⁺ T-cell counts were achieved.