AIDS (London, England) · 2019
E157Q integrase strand-transfer inhibitor substitution in patients with acute/recent HIV infection.
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Ambrosioni Juan, Rico José Ángel Fernández-Caballero, Nicolás David, Mosquera María Mar, de Lazzari Elisa, Marcos María Ángeles, García Federico, Miró José M, Hospital Clinic Acute/Recent HIV infection Study Group
Аннотация
OBJECTIVES: Integrase strand-transfer inhibitor (InSTI)-based regimens are the preferred combinations for naïve HIV-infected individuals. Polymorphic substitutions that reduce InSTIs activity have been described, with E157Q being one of the most frequently found. This study aimed to evaluate the prevalence of E157Q substitution in newly diagnosed acute/recent HIV cases and the presence of transmission clusters.
DESIGN: Prospective cohort study in patients with acute/recent HIV infection.
METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of less than 6 months from May 2015 to May 2017. Sequences were obtained by ultra-deep sequencing. Phylogenetic inferences were performed using maximum likelihood trees constructed with Mega 6.06. Bootstrap values of 75% or greater were defined for cluster assignment. Follow-up was, at least, 1 year.
RESULTS: In six out of 67 consecutive patients (8.95%, 95% confidence interval 4.17-18.19) with acute/recent HIV infection, strains carrying the E157Q InSTI substitution were detected. All cases were MSM patients infected with subtype B strains. No other resistance substitutions were detected in these cases. Median viral load was 5.33 (interquartile range: 4.54-5.71) log10 copies/ml and, in all cases, the mutational viral load was high (>95%). Three cases were included in transmission clusters. Three cases responded to dolutegravir-based regimens; nonnucleoside reverse transcriptase inhibitor-based regimens were used for the other case(s).
CONCLUSION: E157Q substitution, reducing raltegravir and elvitegravir activity, was frequently found in acute/recent HIV cases. All cases were infected with subtype B, and some were included in clusters. Cases treated with dolutegravir-based regimens had good virological response.
DESIGN: Prospective cohort study in patients with acute/recent HIV infection.
METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of less than 6 months from May 2015 to May 2017. Sequences were obtained by ultra-deep sequencing. Phylogenetic inferences were performed using maximum likelihood trees constructed with Mega 6.06. Bootstrap values of 75% or greater were defined for cluster assignment. Follow-up was, at least, 1 year.
RESULTS: In six out of 67 consecutive patients (8.95%, 95% confidence interval 4.17-18.19) with acute/recent HIV infection, strains carrying the E157Q InSTI substitution were detected. All cases were MSM patients infected with subtype B strains. No other resistance substitutions were detected in these cases. Median viral load was 5.33 (interquartile range: 4.54-5.71) log10 copies/ml and, in all cases, the mutational viral load was high (>95%). Three cases were included in transmission clusters. Three cases responded to dolutegravir-based regimens; nonnucleoside reverse transcriptase inhibitor-based regimens were used for the other case(s).
CONCLUSION: E157Q substitution, reducing raltegravir and elvitegravir activity, was frequently found in acute/recent HIV cases. All cases were infected with subtype B, and some were included in clusters. Cases treated with dolutegravir-based regimens had good virological response.
Предметные рубрики MeSH
AdultAmino Acid SubstitutionDisease Transmission, InfectiousDrug Resistance, ViralFemaleGene FrequencyGenotypeGenotyping TechniquesHIVHIV InfectionsHIV IntegraseHIV Integrase InhibitorsHigh-Throughput Nucleotide SequencingHumansMaleMolecular EpidemiologyMutation, MissensePhylogenyPrevalenceProspective StudiesQuinolonesRaltegravir PotassiumSexual and Gender MinoritiesViral Load