TY - JOUR
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 - 2019/6
Y1 - 2019/6
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) 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.
AB - 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.
KW - Drug Resistance, Viral/genetics
KW - Evolution, Molecular
KW - Genotype
KW - HIV Envelope Protein gp120/genetics
KW - HIV Infections/drug therapy
KW - HIV Integrase/genetics
KW - HIV-1/genetics
KW - Heterocyclic Compounds, 3-Ring/therapeutic use
KW - Humans
KW - Peptide Fragments/genetics
KW - Viral Load/genetics
U2 - 10.1007/s11262-019-01649-z
DO - 10.1007/s11262-019-01649-z
M3 - Article
C2 - 30796743
VL - 55
SP - 290
EP - 297
JO - Virus Genes
JF - Virus Genes
SN - 0920-8569
IS - 3
ER -