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- Title
Is there a relationship between HIV tropism and historical genotypic resistance in treatment-experienced patients?
- Authors
Zaccarelli, M; Sterrantino, G; Francisci, D; Di Biagio, A; Di Giambenedetto, S; De Luca, A; Punzi, G; Bruzzone, B; Meini, G; Zazzi, M
- Abstract
Purpose of the study Since X4/DM HIV-1 tropism is associated with poorer prognosis and worse response to treatment, the aim of this study was to assess whether X4/DM HIV-1 tropism is also related with a higher accumulation of resistance in patients experiencing treatment failure. Methods HIV protease (PR) and reverse transcriptase (RT) resistance mutations and tropism test results were extracted from a national database. Viral tropism data included enhanced sensitivity Trofile assay (ESTA) and geno2pheno results at 10% false positive rate. Historical resistance mutations (HRM) for PI, NRTI and NNRTI, detected in all genotypic tests performed during patient treatment history, were selected according to IAS-USA indications. Summary of results Overall, 1280 patients were included: males 65%, median age 45 years (IQR: 40-50), median CD4 nadir 116 (IQR: 34-272), median past regimens 7 (IQR: 3-12), median previous NRTI used 5 (IQR: 4-7), median previous NNRTI used 1 (IQR 1-2) and median previous PI used 3 (IQR 1-5). HIV tropism was assessed by ESTA in 271 patients (21.2%) and by geno2pheno in 1009 patients (78.8%). Four hundred and fifteen patients (32.4%) carried X4/DM virus and 321 (25.1%) had ≥1 HRM for each antiretroviral class. The mean number of HRM was higher in patients harboring X4/DM virus than in patients harboring R5 virus (5.1±6.4 vs. 4.3±5.9, p = 0.02 at ANOVA test). X4/DM strains also harbored a higher mean number of PI-related HRM (1.8±2.8 vs. 1.5±2.6, p = 0.003) and NNRTI-related HRM (1.2±1.6 vs. 0.9±1.4, p = 0.001), but not of NRTI-related HRM (2.2±2.6 vs. 2.0±2.6). At logistic regression, patients with HRM for all the 3 classes had a significant higher risk of also harboring X4/DM virus (OR: 1.6, 95% CI: 1.0-2.4, p = 0.04). Moreover, X4/DM virus was found to be associated with previous use of NNRTI-containing regimens (OR: 1.4, 95% CI: 1.1-1-9, p = 0.03) and lower CD4 nadir (OR: 0.9, 95% CI: 0.9-1.0, p = 0.001, per 50-CD4 increase). The analysis was adjusted by number of genotypic tests, number of treatment lines, age and HV subtype. Single mutations significantly associated with X4/DM tropism were: for PI, V32I and L76V; for NRTI: M41L, K70R, L74V and T215Y and for NNRTI: E138G and V179T. Conclusions Our data suggest that X4/DM tropism is associated with accumulation of resistance mutations during treatment history. X4/DM tropism is also confirmed to be a marker of a more compromised clinical and immune-virological condition.
- Subjects
HEALTH outcome assessment; HIV protease inhibitors; GENOTYPES; HIV infections; VIRAL tropism
- Publication
Journal of the International AIDS Society, 2012, Vol 15, p1
- ISSN
1758-2652
- Publication type
Article
- DOI
10.7448/IAS.15.6.18206