Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice
Articolo
Data di Pubblicazione:
2019
Citazione:
Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice / C. Alteri, R. Scutari, A. Bertoli, D. Armenia, C. Gori, G. Fabbri, C.M. Mastroianni, C. Cerva, A. Cristaudo, I. Vicenti, B. Bruzzone, M. Zazzi, M. Andreoni, A. Antinori, V. Svicher, F. Ceccherini-Silberstein, C.F. Perno, M.M. Santoro. - In: VIRUS GENES. - ISSN 0920-8569. - 55:3(2019 Jul), pp. 290-297. [10.1007/s11262-019-01649-z]
Abstract:
Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral evolution. Here, we assessed the role of INSTIs on HIV-1 V3 evolution in a cohort of 89 HIV-1-infected individuals starting an INSTI- (N = 41, [dolutegravir: N = 1; elvitegravir: N = 3; raltegravir: N = 37]) or a non-INSTI-based (N = 48) combined antiretroviral therapy (cART), with two plasma RNA V3 genotypic tests available (one before [baseline] and one during cART). V3 sequences were analysed for genetic distance (Tajima-Nei model) and positive selection (dN/dS ratio). Individuals were mainly infected by B subtype (71.9%). Median (interquartile-range, IQR) plasma viral load and CD4 + T cell count at baseline were 4.8 (3.5–5.5) log10 copies/mL and 207 (67–441) cells/mm3, respectively. Genetic distance (median, IQR) between the V3 sequences obtained during cART and those obtained at baseline was 0.04 (0.01–0.07). By considering treatment, genetic distance was significantly lower in INSTI-treated than in non-INSTI-treated individuals (median [IQR]: 0.03[0.01–0.04] vs. 0.05[0.02–0.08], p = 0.026). In line with this, a positive selection (defined as dN/dS ≥ 1) was observed in 36.6% of V3 sequences belonging to the INSTI-treated group and in 56.3% of non-INSTI group (p = 0.05). Multivariable logistic regression confirmed the independent correlation of INSTI-based regimens with a lower probability of both V3 evolution (adjusted odds-ratio: 0.35 [confidence interval (CI) 0.13–0.88], p = 0.027) and positive selection (even if with a trend) (adjusted odds-ratio: 0.46 [CI 0.19–1.11], p = 0.083). Overall, this study suggests a role of INSTI-based regimen in limiting HIV-1 V3 evolution over time. Further studies are required to confirm these findings.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
HIV-1; HIV-1 evolution; HIV-1 tropism; Integrase inhibitors; V3; Drug Resistance, Viral; Evolution, Molecular; Genotype; HIV Envelope Protein gp120; HIV Infections; HIV Integrase; HIV-1; Heterocyclic Compounds, 3-Ring; Humans; Peptide Fragments; Viral Load
Elenco autori:
C. Alteri, R. Scutari, A. Bertoli, D. Armenia, C. Gori, G. Fabbri, C.M. Mastroianni, C. Cerva, A. Cristaudo, I. Vicenti, B. Bruzzone, M. Zazzi, M. Andreoni, A. Antinori, V. Svicher, F. Ceccherini-Silberstein, C.F. Perno, M.M. Santoro
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