title: Cellular HIV reservoir replenishment is not affected by blip or intermittent viremia episodes during darunavir/ritonavir monotherapy.
abstract: OBJECTIVE
  To assess the impact of blips and persistent viremia episodes on cell-associated HIV-DNA reservoir in extensively pretreated patients receiving ritonavir-boosted darunavir monotherapy (MtDRV/rtv) for 24 months.
  
  
  METHODS
  Patients from the MonDAR prospective study (NCT01606722) who received at least 6 months of MtDRV/rtv and had at least two available peripheral blood mononuclear cells (PBMCs) samples were selected and classified according to the viral outcome as continuous undetectable viremia (cUV; n = 40), blips (n = 31), intermittent viremia (IV; n = 23), and virological failure (VF, two consecutive viral loads >200 copies/ml; n = 20). Proviral HIV-DNA was quantified by real-time PCR in PBMCs samples at baseline, and months 6, 12, 18 and 24. Additionally, HIV-DNA levels were exhaustively analyzed at virological failure and blip episodes.
  
  
  RESULTS
  The HIV-DNA levels remained constant during the 24 months in every group. Neither blips nor intermittent viremia influenced the HIV-DNA levels at short-term or at middle term. By contrast, virological failure episodes gave rise to a significant increase in proviral DNA (2.15 vs. 2.32 log10 HIV-DNA copies/10 PBMCs; P = 0.042). Basal proviral DNA levels more than 2 log10 copies/10 PBMCs predicted the time to viral rebound at any given cut-off point (>20, >50, and >200 copies/ml. HR: 3.02, 2.61, and 3.02, respectively; P ≤ 0.03. Besides, an adherence less than 95% was also strongly associated with virological failure (HR, 3.17; P = 0.021).
  
  
  CONCLUSIONS
  Blip episodes and intermittent viremia did not affect the cellular HIV reservoir dynamic during MtDRV/rtv. Higher adherence and an HIV-DNA levels less than 2 log10 copies/10 PBMCs at baseline were associated with a lower risk of virological failure.
authors.affiliation: Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot, Sevilla, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Benmarzouk-Hidalgo
authors.forename: Alicia
authors.initials: A
authors.lastname: Gutiérrez-Valencia
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Romero
authors.forename: Reyes
authors.initials: R
authors.lastname: Martín-Peña
authors.forename: Rosa
authors.initials: R
authors.lastname: Ruiz-Valderas
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Cortes
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification*; D000069454:Darunavir; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D060888:Real-Time Polymerase Chain Reaction; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia
chemical_list: D004279:DNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir