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Browsing by Author "Cabanas, Joaquim"

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  • Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 Hepatitis C Virus infected patients in a Portuguese cohort
    Publication . Brandão, Ruben; Marcelino, Rute; Gonçalves, Fátima; Diogo, Isabel; Carvalho, Ana; Cabanas, Joaquim; Costa, Inês; Brogueira, Pedro; Ventura, Fernando; Miranda, Ana; Mansinho, Kamal; Gomes, Perpétua
    This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).
    2018-04Journal article Open access Show more
  • Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure
    Publication . Theys, Kristof; Abecasis, Ana; Libina, Pieter; Gomes, Perpétua; Cabanas, Joaquim; Camacho, Ricardo J.; Van Laethem, Kristel
    BACKGROUND: Dolutegravir is approved for the treatment of HIV-1 patients exposed to other integrase inhibitors, but the decision to use dolutegravir in this setting should be informed by drug resistance testing. OBJECTIVES: This study determined the extent of disagreement in predicted residual dolutegravir activity after raltegravir use, and identified individual mutational patterns for which uncertainty exists among HIV-1 expert systems. STUDY DESIGN: Mutation patterns were classified in raltegravir signature pathways including positions 143, 148 and 155, and interpreted into clinically informative resistance levels using genotypic drug resistance interpretation systems ANRS v24, HIVdb v7.0 and Rega v9.1.0, and instructions of dolutegravir use as approved by the Food and Drug Administration and the European Medicines Agency. RESULTS: In 216HIV-1 patients failing raltegravir-therapy, 87% patients displayed mutations associated with resistance towards integrase inhibitors. A total of 141 unique mutational patterns were observed, with N155H (25.4%), Q148H (16.2%) and Y143R (8.3%) the most prevalent signature mutations. The Q148 pathway occurred almost exclusively in HIV-1 subtype B viruses. Concordances in predicted dolutegravir susceptibility scores among 5 systems were obtained in 57.8% of patients, and concordant intermediate resistant and concordant resistant scores were only observed in 6.5% and 0.9% of patients, respectively. However, systems individually scored higher levels of dolutegravir intermediate resistance and resistance, ranging from 4.2% to 10.2% and from 14.8% to 22.7% of patients, respectively. A consensus on interpreting the extent of residual activity was lacking in 34.7% of patients and was highly resistance pathway-specific. CONCLUSIONS: Dolutegravir may potentially be effective in the majority of HIV-1 patients failing raltegravir, but concern over the uncertainty in predicted residual activity could withhold clinicians from prescribing dolutegravir during its clinical assessment.
    2015-09Journal article Restricted access Show more
  • A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expect
    Publication . Silva, Joana; Pereira, Karen; Rijo, João; Alberto, Teresa; Cabanas, Joaquim; Gomes, Perpétua; Farinha, Helena; Mansinho, Kamal
    Abstracts of the HIV Drug Therapy Glasgow Congress 2014.
    2014-11Journal article Open access Show more
  • Transmitted drug resistance in drug-naïve HIV-2 infected patients
    Publication . Duarte, Frederico; Miranda, Ana Cláudia; Peres, Susana; Diogo, Isabel; Gonçalves, Fátima; Carvalho, Ana Patrícia; Costa, Inês; Cabanas, Joaquim; Moneti, Virgínia; Alves, João Vaz; Abreu, Ricardo Correia de; Neves, Isabela; Aldir, Isabel; Mansinho, Kamal; Gomes, Perpétua
    2016-06Journal article Restricted access Show more