title: Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.
abstract: BACKGROUND
  Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term.
  
  
  OBJECTIVE
  In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy.
  
  
  METHODS
  Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml).
  
  
  RESULTS
  Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery.
  
  
  CONCLUSIONS
  Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.
authors: Department of Clinical Viro-Immunology, CLB, Sanquin Blood Supply Foundation, University of Amsterdam, The Netherlands.
authors: N G
authors: NG
authors: Pakker
authors: E D
authors: ED
authors: Kroon
authors: M T
authors: MT
authors: Roos
authors: S A
authors: SA
authors: Otto
authors: D
authors: D
authors: Hall
authors: F W
authors: FW
authors: Wit
authors: D
authors: D
authors: Hamann
authors: M E
authors: ME
authors: van der Ende
authors: F A
authors: FA
authors: Claessen
authors: R H
authors: RH
authors: Kauffmann
authors: P P
authors: PP
authors: Koopmans
authors: F P
authors: FP
authors: Kroon
authors: C H
authors: CH
authors: ten Napel
authors: H G
authors: HG
authors: Sprenger
authors: H M
authors: HM
authors: Weigel
authors: J S
authors: JS
authors: Montaner
authors: J M
authors: JM
authors: Lange
authors: P
authors: P
authors: Reiss
authors: P T
authors: PT
authors: Schellekens
authors: F
authors: F
authors: Miedema
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016049:Didanosine / Q000627:therapeutic use; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine; D016049:Didanosine