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PLoS One. 2015 Mar 20;10(3):e0120474. doi: 10.1371/journal.pone.0120474. eCollection 2015.

Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.

Author information

1
National Institutes of Health, National Institute of Mental Health, Bethesda MD, United States of America.
2
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston MA, United States of America.
3
Maternal, Child and Adolescent Center for Infectious Diseases and Virology, University of Southern California Keck School of Medicine, Los Angeles CA, United States of America.
4
University of Miami Miller School of Medicine, Miami FL, United States of America.
5
Children's Hospital Boston and Harvard Medical School, Boston MA, United States of America.
6
University of Colorado Denver, Denver CO, United States of America.

Abstract

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)-algorithm study.

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 adjusted models, 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.

PMID:
25794163
PMCID:
PMC4368806
DOI:
10.1371/journal.pone.0120474
[Indexed for MEDLINE]
Free PMC Article

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