The V118I mutation as a marker of advanced HIV infection and disease progression.
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.
Zaccarelli
Mauro
M
Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. zaccarelli@inmi.it
Tozzi
Valerio
V
Lorenzini
Patrizia
P
Forbici
Federica
F
Narciso
Pasquale
P
Ceccherini-Silberstein
Francesca
F
Trotta
Maria Paola
MP
Bertoli
Ada
A
Liuzzi
Giuseppina
G
Marconi
Patrizia
P
Mosti
Silvia
S
Perno
Carlo Federico
CF
Antinori
Andrea
A
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
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D007532:Isoleucine; D054303:HIV Reverse Transcriptase; D014633:Valine