title: Impact of raltegravir on HIV-1 RNA and DNA forms following initiation of antiretroviral therapy in treatment-naive patients.
abstract: OBJECTIVE
  The rapid early-phase decay of plasma HIV-1 RNA during integrase inhibitor-based therapy is not fully understood. The accumulation of biologically active episomal HIV-1 cDNAs, following aborted integration, could contribute to antiviral potency in vivo.
  
  
  METHODS
  This prospective, controlled clinical observation study explored raltegravir's impact on the dynamics of HIV-1 RNA in plasma, and concentrations of total HIV-1 cDNA, episomal 2-long terminal repeat (LTR) circles and HIV-1 integrants in peripheral blood mononuclear cells (PBMC). Individuals starting therapy with two nucleoside reverse transcriptase inhibitors plus either raltegravir (raltegravir group; n = 10 patients) or boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitor (control group; n = 10 patients) were followed for 48 weeks.
  
  
  RESULTS
  Suppression of HIV-1 RNA (<50 copies/mL) was reached earlier (5/10 versus 0/10 at week 4; 8/10 versus 4/10 at week 12) on raltegravir. Significant total HIV-1 cDNA reductions in PBMC were reached by day 99 and persisted until day 330, with median factors of decrease of 7.2 and 8.9, respectively. Broad inter-individual variations, yet no treatment-associated differences, were noted for HIV-1 cDNA concentrations. Despite reductions in HIV-1 RNA (∼3 log) and total HIV-1 cDNA (∼1 log), concentrations of integrants and 2-LTR circles remained largely unchanged.
  
  
  CONCLUSIONS
  These results extend the previously reported early benefit of raltegravir on the decline of plasma viraemia to treatment-naive patients. The modest treatment-associated, yet group-independent, decline in total HIV-1 cDNA load and the lack of significant changes in integrated and episomal HIV-1 cDNA suggest that most integrated DNA is archival and targeting of HIV reservoirs other than PBMC may underlie beneficial effects of raltegravir.
authors: Medical Department no. 2, Infectious Diseases Unit, University Hospital Frankfurt, Frankfurt, Germany.
authors: Christoph
authors: C
authors: Stephan
authors: Institute of Medical Virology, National Reference Center for Retroviruses, University Hospital Frankfurt, Frankfurt, Germany Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany.
authors: Hanna-Mari
authors: HM
authors: Baldauf
authors: VIROQUANT Research Group Modeling, Bioquant BQ0026, University of Heidelberg, Heidelberg, Germany Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany.
authors: Joanne
authors: J
authors: Barry
authors: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors: Frank A
authors: FA
authors: Giordano
authors: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors: Cynthia C
authors: CC
authors: Bartholomae
authors: Medical Department no. 2, Infectious Diseases Unit, University Hospital Frankfurt, Frankfurt, Germany.
authors: Annette
authors: A
authors: Haberl
authors: Medical Department no. 2, Infectious Diseases Unit, University Hospital Frankfurt, Frankfurt, Germany.
authors: Markus
authors: M
authors: Bickel
authors: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors: Manfred
authors: M
authors: Schmidt
authors: Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors: Stephanie
authors: S
authors: Laufs
authors: VIROQUANT Research Group Modeling, Bioquant BQ0026, University of Heidelberg, Heidelberg, Germany Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany.
authors: Lars
authors: L
authors: Kaderali
authors: Institute of Medical Virology, National Reference Center for Retroviruses, University Hospital Frankfurt, Frankfurt, Germany Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany oliver.keppler@kgu.de.
authors: Oliver T
authors: OT
authors: Keppler
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011533:Proviruses; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use*; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019562:Viral Load; D016662:Virus Integration; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium
keywords: 2-LTR circles; antiretroviral therapy; decay; episomal DNA; integrase inhibitor; slope; viral dynamics; virus load