TY - JOUR
T1 - Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy
AU - Pediatric AIDS Clinical Trials Group Protocol 366
AU - Kapetanovic, Suad
AU - Aaron, Lisa
AU - Montepiedra, Grace
AU - Anthony, Patricia
AU - Thuvamontolrat, Kasalyn
AU - Pahwa, Savita
AU - Burchett, Sandra
AU - Weinberg, Adriana
AU - Kovacs, Andrea
N1 - Publisher Copyright:
© 2015, Public Library of Science. All rights reserved.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2015/3/20
Y1 - 2015/3/20
N2 - Background: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithmstudy. Methods: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49%CMV+ aviremic; 37% CMV-naïve. In longitudinal adjustedmodels, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L +CD45RA+%and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.
AB - Background: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithmstudy. Methods: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49%CMV+ aviremic; 37% CMV-naïve. In longitudinal adjustedmodels, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L +CD45RA+%and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.
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U2 - 10.1371/journal.pone.0120474
DO - 10.1371/journal.pone.0120474
M3 - Article
C2 - 25794163
AN - SCOPUS:84925690301
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e0120474
ER -