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Percorrer por autor "Cabanas, Joaquim"

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  • Applying next-generation sequencing to track HIV-1 drug resistance mutations circulating in Portugal
    Publication . Pimentel, Victor; Pingarilho, Marta; Sebastião, Cruz S.; Miranda, Mafalda; Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Diogo, Isabel; Fernandes, Sandra; Costa, Olga; Corte-Real, Rita; Martins, M. Rosário O.; Seabra, Sofia G.; Abecasis, Ana B.; Gomes, Perpétua
    Background: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission. Objective: We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal. Methods: Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay. Results: About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs. Conclusions: We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir).
    2024-04Contributo em revista Acesso aberto Ver mais
  • 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).
    2018-04Artigo científico Acesso aberto Ver mais
  • 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.
    2015-09Artigo científico Acesso restrito Ver mais
  • Emerging patterns in HIV integrase resistance
    Publication . Veloso, Margarida; Ribeiro, Marta; Cabanas, Joaquim; Gonçalves, Fátima; Fernandes, Sandra; Diogo, Isabel; Costa, Inês; Pimentel, Victor; Pingarilho, Marta; Abecasis, Ana; Gomes, Perpétua
    We assessed integrase resistance in 837 treatment-experienced people with HIV (PWH) with virological failure (2022–2024) in Portugal. Major resistance mutations were found in 5.5%, with N155H and R263K being the most common. Resistance was more frequent in non-B subtypes and often co-occurred with resistance to other antiretroviral classes. Though prevalence remains low, the findings highlight the need for continued surveillance to inform treatment decisions, especially as integrase inhibitors like dolutegravir, bictegravir and cabotegravir become more widely used.
    2025-12Contributo em revista Acesso aberto Ver mais
  • HIV-1 late diagnosis : strategies to overcome the misclassification of individuals acutely infected with HIV-1 as individuals diagnosed late
    Publication . Miranda, Mafalda N. S.; Pimentel, Victor; Santos, André; Alemão, André; Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Diogo, Isabel; Fernandes, Sandra; Seabra, Sofia G.; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana; on behalf of the Portuguese HIV-1 Resistance Study Group
    Objectives: Late HIV diagnosis is associated with a higher impact on treatment outcomes and a potential for prolonged transmissibility of HIV-1 infection. The consensus definition for late HIV diagnosis is problematic. It was updated in 2022; however, this definition relies on information that might not be clinically available. This study aimed to assess late HIV diagnosis using alternative parameters, in addition to the definition of clusters of differentiation (CD4) cell count, namely, sequence ambiguity rate and estimated time of infection inferred through phylogenetic analysis. Methods: Clinical, socio-demographic, and genotypic information from 3668 antiretroviral therapy–naïve individuals living with HIV was retrieved from the REGA database. Individuals were classified according to three approaches: (i) CD4 cell count, (ii) sequence ambiguity rate, and (iii) phylogenetic reconstruction using TreeTime to estimate the time of most recent common ancestor (MRCA) as a proxy for time of infection. Results: Based on CD4 cell count, 53.8% of individuals had a late diagnosis and 46.2% had a non-late diagnosis. Based on sequence ambiguity rate, 57.8% had a chronic and 42.2% had a recent infection, and 86.4% had an estimated time of infection of more than 3 years, whereas 13.6% had less than 3 years. A total of 114 individuals were classified as diagnosed late by CD4 criteria and showed evidence of recent infection based on low ambiguity rates and MRCA estimates under 3 years. These individuals had significantly lower viral loads than those with true late diagnoses (median 61,358 vs 134,730 copies/ml; P <0.001). Overall, 41% of individuals were consistently classified across all three methods. Conclusions: The definition of late diagnosis remains a major challenge. Alternative and complementary methods, such as the use of viral loads, combined with some more clinical information, may improve the lack of baseline data.
    2026-04Contributo em revista Acesso aberto Ver mais
  • Hybrid next-generation sequencing protocol for testing HIV-2 drug resistance
    Publication . Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Veloso, Margarida; Ribeiro, Marta; Fernandes, Sandra; Diogo, Isabel; Sebastião, Cruz S.; Pingarilho, Marta; Pimentel, Victor; Abecasis, Ana; Gomes, Perpétua
    HIV-2 affects over 1 million people globally and can lead to AIDS if untreated. Treating people living with HIV-2 (PLHIV-2) is challenging because the virus is inherently resistant to some drugs. Effective treatment monitoring, particularly drug resistance testing, is critical for managing therapeutic failure. Without commercial tests to identify drug resistance mutations (DRM), laboratories have felt the need to develop in-house methods. NGS provides improved sensitivity for detecting minority DRM, which is crucial for effectively treating individuals, especially with limited therapeutic options. This study aimed to evaluate the effectiveness of a hybrid NGS Ion Torrent protocol for the detection of DRM in PLHIV-2 and its use in clinical practice. One hundred samples from PLHIV-2 collected from hospitals across Portugal were analyzed using a hybrid NGS protocol. Of these, 48 samples were also subjected to Sanger sequencing for comparative purposes. NGS successfully amplified 92 % of protease, 91 % of reverse transcriptase, and 49 % of integrase regions. The two sequencing methods agreed on the majority of DRM identified, with the only difference in two samples for the reverse transcriptase, which NGS identified as K70E and M184V, while Sanger did not. Hybrid NGS was able to identify DRM, demonstrating strong statistical agreement. In conclusion, hybrid NGS detected all DRM identified by Sanger, with the added ability to detect minority variants. The implementation of NGS-based protocol can provide clinicians with more comprehensive data, allowing for adjustments to ART regimens, and ultimately improving patient outcomes and quality of care for PLHIV-2.
    2025-05Contributo em revista Acesso aberto Ver mais
  • 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.
    2014-11Artigo científico Acesso aberto Ver mais
  • 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
    2016-06Artigo científico Acesso restrito Ver mais