title: Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART.
abstract: BACKGROUND
  Raltegravir is the first approved antiretroviral able to prevent HIV genome integration into the host chromosomes. The aim of the study is to test if raltegravir plasma concentrations can be associated with proviral DNA decline during raltegravir-based salvage therapy.
  
  
  METHODS
  A total of 33 multidrug-resistant HIV-infected patients were enrolled in a longitudinal open-label pilot study and completed a 24-week follow-up. The CD4(+) T-cell count, plasma viral load, proviral HIV DNA and two-long-terminal repeat (2-LTR) circular forms were assessed at baseline, day 14, 30, 60, 90 and 180. The raltegravir trough concentration (C (trough)) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir C (trough).
  
  
  RESULTS
  The mean±SD values of baseline HIV RNA, CD4(+) T-cell count and HIV DNA were 4.4±0.82 log copies/ml, 256±177 cells/mm(3) , and 2,668±4,721 copies/10(6) peripheral blood mononuclear cells, respectively. Despite a transient increase of total DNA at week 2, a marked proviral DNA decay (P=0.01) with an increase of the 2-LTR unintegrated/total DNA ratio (P=0.06) over time was observed. At univariate analysis, no correlation between raltegravir C(trough) and classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying C(trough)<158 ng/ml with respect to those with C(trough)>158 ng/ml (P=0.046).
  
  
  CONCLUSIONS
  Successful raltegravir-based therapy produces a significant decline in proviral DNA and is associated with an increase of the unintegrated/total DNA ratio. Further studies are necessary to define the possible role of pharmacokinetic raltegravir monitoring and the biological meaning of unintegrated proviral DNA.
authors: National Institute for Infectious Diseases, IRCCS Lazzaro Spallanzani, Rome, Italy. emanuele.nicastri@inmi.it
authors: Emanuele
authors: E
authors: Nicastri
authors: Chiara
authors: C
authors: Tommasi
authors: Isabella
authors: I
authors: Abbate
authors: Stefano
authors: S
authors: Bonora
authors: Massimo
authors: M
authors: Tempestilli
authors: Rita
authors: R
authors: Bellagamba
authors: Magdalena
authors: M
authors: Viscione
authors: Gabriella
authors: G
authors: Rozera
authors: Anna L
authors: AL
authors: Gallo
authors: Jelena
authors: J
authors: Ivanovic
authors: Alessandra
authors: A
authors: Amendola
authors: Leopoldo
authors: L
authors: Pucillo
authors: Giovanni
authors: G
authors: Di Perri
authors: Maria R
authors: MR
authors: Capobianchi
authors: Pasquale
authors: P
authors: Narciso
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000187:drug effects* / Q000235:genetics; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019562:Viral Load; D016662:Virus Integration / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium