title: Effect of cytomegalovirus co-infection on normalization of selected T-cell subsets in children with perinatally acquired HIV infection treated with combination antiretroviral therapy.
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.
authors: National Institutes of Health, National Institute of Mental Health, Bethesda MD, United States of America.
authors: Suad
authors: S
authors: Kapetanovic
authors: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston MA, United States of America.
authors: Lisa
authors: L
authors: Aaron
authors: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston MA, United States of America.
authors: Grace
authors: G
authors: Montepiedra
authors: 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.
authors: Patricia
authors: P
authors: Anthony
authors: 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.
authors: Kasalyn
authors: K
authors: Thuvamontolrat
authors: University of Miami Miller School of Medicine, Miami FL, United States of America.
authors: Savita
authors: S
authors: Pahwa
authors: Children's Hospital Boston and Harvard Medical School, Boston MA, United States of America.
authors: Sandra
authors: S
authors: Burchett
authors: University of Colorado Denver, Denver CO, United States of America.
authors: Adriana
authors: A
authors: Weinberg
authors: 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.
authors: Andrea
authors: A
authors: Kovacs
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D002140:California; D002648:Child; D002675:Child, Preschool; D060085:Coinfection; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D015703:Antigens, CD