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) log 10 copies/mL and 207 (67–441) cells/mm 3 , 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
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Integrases
HIV-1
Viral Load
Odds Ratio
Confidence Intervals
Virus Integration
CD4 Lymphocyte Count
Therapeutics
Logistic Models
RNA
T-Lymphocytes

Keywords

  • HIV-1
  • HIV-1 evolution
  • HIV-1 tropism
  • Integrase inhibitors
  • V3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Virology

Cite this

Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice. / Alteri, Claudia; Scutari, Rossana; Bertoli, Ada; Armenia, Daniele; Gori, Caterina; Fabbri, Gabriele; Mastroianni, Claudio Maria; Cerva, Carlotta; Cristaudo, Antonio; Vicenti, Ilaria; Bruzzone, Bianca; Zazzi, Maurizio; Andreoni, Massimo; Antinori, Andrea; Svicher, Valentina; Ceccherini-Silberstein, Francesca; Perno, Carlo Federico; Santoro, Maria Mercedes.

In: Virus Genes, 01.01.2019, p. 290-297.

Research output: Contribution to journalArticle

Alteri, C, Scutari, R, Bertoli, A, Armenia, D, Gori, C, Fabbri, G, Mastroianni, CM, Cerva, C, Cristaudo, A, Vicenti, I, Bruzzone, B, Zazzi, M, Andreoni, M, Antinori, A, Svicher, V, Ceccherini-Silberstein, F, Perno, CF & Santoro, MM 2019, 'Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice', Virus Genes, pp. 290-297. https://doi.org/10.1007/s11262-019-01649-z
Alteri, Claudia ; Scutari, Rossana ; Bertoli, Ada ; Armenia, Daniele ; Gori, Caterina ; Fabbri, Gabriele ; Mastroianni, Claudio Maria ; Cerva, Carlotta ; Cristaudo, Antonio ; Vicenti, Ilaria ; Bruzzone, Bianca ; Zazzi, Maurizio ; Andreoni, Massimo ; Antinori, Andrea ; Svicher, Valentina ; Ceccherini-Silberstein, Francesca ; Perno, Carlo Federico ; Santoro, Maria Mercedes. / Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice. In: Virus Genes. 2019 ; pp. 290-297.
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T1 - Integrase strand transfer inhibitor-based regimen is related with a limited HIV-1 V3 loop evolution in clinical practice

AU - Alteri, Claudia

AU - Scutari, Rossana

AU - Bertoli, Ada

AU - Armenia, Daniele

AU - Gori, Caterina

AU - Fabbri, Gabriele

AU - Mastroianni, Claudio Maria

AU - Cerva, Carlotta

AU - Cristaudo, Antonio

AU - Vicenti, Ilaria

AU - Bruzzone, Bianca

AU - Zazzi, Maurizio

AU - Andreoni, Massimo

AU - Antinori, Andrea

AU - Svicher, Valentina

AU - Ceccherini-Silberstein, Francesca

AU - Perno, Carlo Federico

AU - Santoro, Maria Mercedes

PY - 2019/1/1

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N2 - 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) log 10 copies/mL and 207 (67–441) cells/mm 3 , 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.

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