TY - JOUR
T1 - The Immunological and Virological Consequences of Planned Treatment Interruptions in Children with HIV Infection
AU - Klein, Nigel
AU - Sefe, Delali
AU - Mosconi, Ilaria
AU - Zanchetta, Marisa
AU - Castro, Hannah
AU - Jacobsen, Marianne
AU - Jones, Hannah
AU - Bernardi, Stefania
AU - Pillay, Deenan
AU - Giaquinto, Carlo
AU - Walker, A. Sarah
AU - Gibb, Diana M.
AU - De Rossi, Anita
PY - 2013/10/23
Y1 - 2013/10/23
N2 - Objectives:To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV.Design:This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children.Methods:HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks.Results:In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naïve and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA.Conclusions:PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naïve CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.
AB - Objectives:To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV.Design:This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children.Methods:HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks.Results:In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naïve and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA.Conclusions:PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naïve CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.
UR - http://www.scopus.com/inward/record.url?scp=84886255436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886255436&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0076582
DO - 10.1371/journal.pone.0076582
M3 - Article
C2 - 24194841
AN - SCOPUS:84886255436
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e76582
ER -