title: Stable HIV-1 integrase diversity during initial HIV-1 RNA decay suggests complete blockade of plasma HIV-1 replication by effective raltegravir-containing salvage therapy.
abstract: BACKGROUND
  There is legitimate concern that minority drug-resistant mutants may be selected during the initial HIV-1 RNA decay phase following antiretroviral therapy initiation, thus undermining efficacy of treatment. The goal of this study was to characterize viral resistance emergence and address viral population evolution during the first phase of viral decay after treatment containing initiation.
  
  
  RESULTS
  454 sequencing was used to characterize viral genetic diversity and polymorphism composition of the HIV-1 integrase gene during the first two weeks following initiation of raltegravir-containing HAART in four ART-experienced subjects. No low-prevalence Raltegravir (RAL) drug resistance mutations (DRM) were found at baseline. All patients undergoing treatment received a fully active ART according to GSS values (GSS ≥ 3.5). No emergence of DRM after treatment initiation was detected. Longitudinal analysis showed no evidence of any other polymorphic mutation emergence or variation in viral diversity indexes.
  
  
  CONCLUSIONS
  This suggests that fully active salvage antiretroviral therapy including raltegravir achieves a complete blockade of HIV-1 replication in plasma. It is unlikely that raltegravir-resistant HIV-1 may be selected in plasma during the early HIV-1 RNA decay after treatment initiation if the administered therapy is active enough.
authors.affiliation: IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Universitari Germans Trias I Pujol, Ctra de Canyet s/n, Badalona 08916, Catalonia, Spain. mnoguera@irsicaixa.es.
authors.forename: Marc
authors.initials: M
authors.lastname: Noguera-Julian
authors.forename: Maria
authors.initials: M
authors.lastname: Casadellà
authors.forename: Christian
authors.initials: C
authors.lastname: Pou
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Susana
authors.initials: S
authors.lastname: Pérez-Álvarez
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D011760:Pyrrolidinones / Q000008:administration & dosage*; D020871:RNA Stability; D012367:RNA, Viral / Q000235:genetics; D000068898:Raltegravir Potassium; D016879:Salvage Therapy / Q000379:methods*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1