Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice

Claudia Alteri, Rossana Scutari, Ada Bertoli, Daniele Armenia, Caterina Gori, Gabriele Fabbri, Claudio Maria Mastroianni, Carlotta Cerva, Antonio Cristaudo, Ilaria Vicenti, Bianca Bruzzone, Maurizio Zazzi, Massimo Andreoni, Andrea Antinori, Valentina Svicher, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Maria Mercedes Santoro

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)290-297
Number of pages8
JournalVirus Genes
Volume55
Issue number3
DOIs
Publication statusPublished - Jun 2019

Keywords

  • Drug Resistance, Viral/genetics
  • Evolution, Molecular
  • Genotype
  • HIV Envelope Protein gp120/genetics
  • HIV Infections/drug therapy
  • HIV Integrase/genetics
  • HIV-1/genetics
  • Heterocyclic Compounds, 3-Ring/therapeutic use
  • Humans
  • Peptide Fragments/genetics
  • Viral Load/genetics

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    Alteri, C., Scutari, R., Bertoli, A., Armenia, D., Gori, C., Fabbri, G., Mastroianni, C. M., Cerva, C., Cristaudo, A., Vicenti, I., Bruzzone, B., Zazzi, M., Andreoni, M., Antinori, A., Svicher, V., Ceccherini-Silberstein, F., Perno, C. F., & Santoro, M. M. (2019). Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice. Virus Genes, 55(3), 290-297. https://doi.org/10.1007/s11262-019-01649-z