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Published on: January 7, 2019
Incomplete immune reconstitution despite virologic suppression in HIV-1 infected children and adolescents
Paul Krogstad1, Kunjal Patel, Brad Karalius
1aDepartment of Pediatrics (Infectious Diseases) bDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California cDepartment of Epidemiology, Center for Biostatistics in AIDS Research (CBAR), Harvard School of Public Health, Boston, Massachusetts dEunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda, Maryland eUniversity of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado fDepartment of Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey gNew York University School of Medicine hAlbert Einstein College of Medicine, New York City, New York, USA iDepartment of Pediatrics, Federal University of Minas Gerais, Minas Gerais, Brazil jTulane University School of Medicine, New Orleans, Louisiana, USA.
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/microl.
Results:
After 1 year of virologic suppression, most (99%) children achieved a CD4(+) T-cell count of at least 200 cells/microl, but CD4(+) T-cell counts remained below 500 cells/microl 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/microl were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/microl 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/microl 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.
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