title: The V118I mutation as a marker of advanced HIV infection and disease progression.
abstract: BACKGROUND
  The V118I mutation is included in the nucleoside analogue mutations (NAMs) set. It contributes to thymidine-analogue resistance and, consequently, to resistance to the whole nucleoside reverse transcriptase inhibitor (NRTI) class. We focused on the V1181 mutation in order to evaluate factors associated with its detection and its relationship with HIV progression.
  
  
  METHODS
  Clinical and laboratory data at genotypic resistance test (GRT) of highly active antiretroviral therapy-failing patients were collected and their association with the V1181 mutation was analysed. Patients were also followed over time to determine factors related to progression to a new AIDS-related event or death.
  
  
  RESULTS
  Of the 792 patients included, 114 (14.4%) carried the V118I mutation. In univariate analysis, the V118I mutation was significantly associated with a higher HIV RNA level, lower CD4+ T-cell count, Centers for Disease Control and Prevention (CDC) stage C, higher number of pre-GRT regimens and class-wide resistance (CWR) to NRTIs, protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Higher numbers of pre-GRT regimens and NRTI CWR were also associated in the multivariable analysis. Within the post-GRT observation period of up to 6 years (median: 72 months; interquartile range: 33-109) 107 events (58 new AIDS-related diseases and 49 deaths) were observed. Using the Cox proportional hazard model and the major clinical, behavioural and laboratory data, the V118I mutation was found to be associated with the endpoint (hazard ratio: 1.93, 95% confidence interval: 1.06-3.50; P=0.031). Other factors associated with disease progression were CDC stage C and lower CD4+ T-cell count at GRT.
  
  
  CONCLUSIONS
  The analysis of our observational database suggests that the onset of the V118I mutation after treatment failure is unfavourable for the patient and can be considered a strong marker of disease progression.
authors.affiliation: Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. zaccarelli@inmi.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Valerio
authors.initials: V
authors.lastname: Tozzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lorenzini
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.forename: Pasquale
authors.initials: P
authors.lastname: Narciso
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Trotta
authors.forename: Ada
authors.initials: A
authors.lastname: Bertoli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Liuzzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Marconi
authors.forename: Silvia
authors.initials: S
authors.lastname: Mosti
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D018450:Disease Progression; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007532:Isoleucine; D016015:Logistic Models; D008297:Male; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure; D014633:Valine
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D007532:Isoleucine; D054303:HIV Reverse Transcriptase; D014633:Valine