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

Abstract

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/μl.

Results: After 1 year of virologic suppression, most (99%) children achieved a CD4(+) T-cell count of at least 200 cells/μl, but CD4(+) T-cell counts remained below 500 cells/μl after 1 and 2 years of virologic suppression in 14 and 8% of children, respectively. Median times to first CD4(+) T-cell count at least 500 cells/μl were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/μl 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 500 cells/μl 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.

Figure 1

Tempo of immune reconstitution during periods of virological suppression. A. CD4 count (cells/μL) means over follow-up, by CD4 count at the start of the virologic suppression periods. B. Kaplan-Meier survival curves for time to first CD4 count ≥500 cells/μL, by CD4 count at the start of the virologic suppression period.

Figure 2

Development of low CD4 counts and serious clinical events during virologic suppression. A. Kaplan-Meier survival curves for time to first sustained low CD4 count outcome, among subjects with CD4 ≥ 500 at the start of the virologic suppression period. B. New Clinical Events (CDC C and non-AIDS defining) during the first three years of study follow-up, by CD4 count at event. Only first clinical event for an individual is shown