Background: Transmitted drug resistance (TDR) in antiretroviral (ART)-naïve patients remains a serious concern since it can reduce the efficacy of treatment and may affect clinical outcomes. The aim of this retrospective study is to describe circulating viral subtypes and evaluate the prevalence of TDR in drug naïve patients from Sapienza University Hospital. Materials/methods: Genotypic resistance tests (GRT) of 668 ART-naïve patients attending Sapienza University Hospital, Rome, between 2005 and 2017 were analyzed. GRT were conducted in integrase (n= 52), protease and reverse transcriptase (RT) (n=668) sequences (Trugene® HIV-1 Genotyping Kit, Siemens; ViroSeq™ HIV-1 Genotyping System, Abbott). Results: Most of patients were male (76.1%), of Italian origin (70.9%), with a median age of 38 years (IQR 31- 48 years); the median viral load was 4.7 log10 copies/mL (IQR 4.1-5.3) and the mean baseline CD4 cell count was 352 cells/mm3 (IQR 148-570). Phylogenetic analysis revealed the presence of 21 different subtypes and Circulating Recombinant Forms (CRFs). Subtype B was most common (67.1%), followed by CRF02_AG (8.4%), subtypes C and F (6%). A significantly increased overtime in the proportion of non-B strains (p<0.001) and in the rates of nonItalians patients (p<0.001) was found. Most individuals (92.7%) had no TDR mutations and were susceptible to all drugs. The overall prevalence of TDR was 9.4% [nucleoside reverse transcriptase inhibitors (NRTIs)= 4.2%, non-nucleoside reverse transcriptase inhibitors (NNRTIs)= 5.8%, protease inhibitors (PIs)= 1.0%] and was higher in subtype B strains. The most common resistant mutations were K103N (1.9%) and T215D/S (1.5%) in RT region and M46I (0.4%) in protease. Among integrase resistance mutations,7 individuals had a minor or accessory mutation and 2 showed major mutations. Among the minor mutations, T97A and G140S were detected in 3 and 2 patients respectively; E138K occurred in 1 individual. Interestingly, 2 patients harbored the major Q148H and the minor G140S mutation and share also the reverse transcriptase mutations (E138G, T215S, H221Y, M230L). These individuals were a couple, both active drug users and in acute phase of infection. Phylogenetic analysis confirmed that these patients harboring the same virus. No significant decrease of TDR was documented overtime. Conclusions: TDR rate observed in our population is in agreement with the average rate in Europe. The lack of a significant reduction of TDR underlines the importance of a continuous surveillance of resistance mutations. These data on INSTI mutations reinforce the recommendations to perform INSTI GRT before commencing treatment, especially in those presenting resistance to other classes of drugs and in difficult population like active drug users. Moreover, the significant increase of non-B viruses suggests the importance to monitor dynamics of HIV transmission, since this may have important clinical and diagnostic implications

HIV-1 DIVERSITY AND ANTIRETROVIRAL RESISTANCE MUTATIONS AMONG TREATMENT NAÏVE PATIENTS FROM 2005-2017: A SINGLE CENTER EXPERIENCE / Mazzuti, Laura; Falasca, Francesca; Melengu, Taulant; DI CARLO, Daniele; Sciandra, Ilaria; Calabretto, Marianna; Mezzaroma, Ivano; D'Ettorre, Gabriella; Cella, Eleonora; Caterina, Fimiani; Giancarlo, Iaiani; Antonelli, Guido; Turriziani, Ombretta. - (2018). ((Intervento presentato al convegno 2nd national ISV Congress 2018 tenutosi a Roma, Italia.

HIV-1 DIVERSITY AND ANTIRETROVIRAL RESISTANCE MUTATIONS AMONG TREATMENT NAÏVE PATIENTS FROM 2005-2017: A SINGLE CENTER EXPERIENCE

Laura Mazzuti;Francesca Falasca;Taulant Melengu;Daniele Di Carlo;Ilaria Sciandra;CALABRETTO, MARIANNA;Ivano Mezzaroma;Gabriella d'ettorre;Eleonora Cella;Guido Antonelli;Ombretta Turriziani
2018

Abstract

Background: Transmitted drug resistance (TDR) in antiretroviral (ART)-naïve patients remains a serious concern since it can reduce the efficacy of treatment and may affect clinical outcomes. The aim of this retrospective study is to describe circulating viral subtypes and evaluate the prevalence of TDR in drug naïve patients from Sapienza University Hospital. Materials/methods: Genotypic resistance tests (GRT) of 668 ART-naïve patients attending Sapienza University Hospital, Rome, between 2005 and 2017 were analyzed. GRT were conducted in integrase (n= 52), protease and reverse transcriptase (RT) (n=668) sequences (Trugene® HIV-1 Genotyping Kit, Siemens; ViroSeq™ HIV-1 Genotyping System, Abbott). Results: Most of patients were male (76.1%), of Italian origin (70.9%), with a median age of 38 years (IQR 31- 48 years); the median viral load was 4.7 log10 copies/mL (IQR 4.1-5.3) and the mean baseline CD4 cell count was 352 cells/mm3 (IQR 148-570). Phylogenetic analysis revealed the presence of 21 different subtypes and Circulating Recombinant Forms (CRFs). Subtype B was most common (67.1%), followed by CRF02_AG (8.4%), subtypes C and F (6%). A significantly increased overtime in the proportion of non-B strains (p<0.001) and in the rates of nonItalians patients (p<0.001) was found. Most individuals (92.7%) had no TDR mutations and were susceptible to all drugs. The overall prevalence of TDR was 9.4% [nucleoside reverse transcriptase inhibitors (NRTIs)= 4.2%, non-nucleoside reverse transcriptase inhibitors (NNRTIs)= 5.8%, protease inhibitors (PIs)= 1.0%] and was higher in subtype B strains. The most common resistant mutations were K103N (1.9%) and T215D/S (1.5%) in RT region and M46I (0.4%) in protease. Among integrase resistance mutations,7 individuals had a minor or accessory mutation and 2 showed major mutations. Among the minor mutations, T97A and G140S were detected in 3 and 2 patients respectively; E138K occurred in 1 individual. Interestingly, 2 patients harbored the major Q148H and the minor G140S mutation and share also the reverse transcriptase mutations (E138G, T215S, H221Y, M230L). These individuals were a couple, both active drug users and in acute phase of infection. Phylogenetic analysis confirmed that these patients harboring the same virus. No significant decrease of TDR was documented overtime. Conclusions: TDR rate observed in our population is in agreement with the average rate in Europe. The lack of a significant reduction of TDR underlines the importance of a continuous surveillance of resistance mutations. These data on INSTI mutations reinforce the recommendations to perform INSTI GRT before commencing treatment, especially in those presenting resistance to other classes of drugs and in difficult population like active drug users. Moreover, the significant increase of non-B viruses suggests the importance to monitor dynamics of HIV transmission, since this may have important clinical and diagnostic implications
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1286184
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