title: Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy.
abstract: BACKGROUND
  Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined.
  
  
  METHODS
  For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels </=200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months.
  
  
  RESULTS
  During follow-up, 33 patients had HIV RNA levels </=20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05).
  
  
  CONCLUSIONS
  These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Terese L
authors.initials: TL
authors.lastname: Katzenstein
authors.forename: Per T
authors.initials: PT
authors.lastname: Thim
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral