Percorrer por autor "Abecasis, Ana"
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- Accidental father-to-son HIV-1 transmission during the seroconversion periodPublication . Ezeonwumelu, Ifeanyi; Bártolo, Inês; Martin, Francisco; Abecasis, Ana; Campos, Teresa; Romero-Severson, Ethan O.; Leitner, Thomas; Taveira, NunoA 4-year-old child born to an HIV-1 seronegative mother was diagnosed with HIV-1, the main risk factor being transmission from the child's father who was seroconverting at the time of the child's birth. In the context of a forensic investigation, we aimed to identify the source of infection of the child and date of the transmission event. Samples were collected from the father and child at two time points about 4 years after the child's birth. Partial segments of three HIV-1 genes (gag, pol, and env) were sequenced and maximum likelihood (ML) and Bayesian methods were used to determine direction and estimate date of transmission. Neutralizing antibodies were determined using a single cycle assay. Bayesian trees displayed a paraphyletic–monophyletic topology in all three genomic regions, with the father's host label at the root, which is consistent with father-to-son transmission. ML trees found similar topologies in gag and pol and a monophyletic–monophyletic topology in env. Analysis of the time of the most recent common ancestor of each HIV-1 gene population indicated that the child was infected shortly after the father. Consistent with the infection history, both father and son developed broad and potent HIV-specific neutralizing antibody responses. In conclusion, the direction of transmission implicated the father as the source of transmission. Transmission occurred during the seroconversion period when the father was unaware of the infection and was likely accidental. This case shows how genetic, phylogenetic, and serological data can contribute for the forensic investigation of HIV transmission.
- Cruising Venues as a Context for HIV Risky Behavior Among Men Who Have Sex With MenPublication . Gama, Ana; Abecasis, Ana; Pingarilho, Marta; Mendão, Luís; Martins, Maria O.; Barros, Henrique; Dias, SóniaWe examined differences in sexual risk behaviors, HIV prevalence, and demographic characteristics between men who have sex with men (MSM) who visit different types of venues to meet sexual partners, and identified correlates of high-risk behaviors. A cross-sectional behavioral survey was conducted with a venue-based sample of 1011 MSM in Portugal. Overall, 36.3 % of MSM usually visit cruising venues to meet sexual partners (63.7 % only visit social gay venues). Cruising venues' visitors reported higher HIV prevalence (14.6 % [95 % CI 11-18 %] vs. 5.5 % [95 % CI 4-7 %]). Visiting cruising venues was more likely among those older, reporting high number of male sexual partners, group sex, and unprotected anal sex with a partner whose HIV status was unknown. Cruising venues play an important role in increasing risk of HIV transmission among MSM who frequent them. Venue-focused behavioral interventions that promote healthy sexual behaviors are needed.
- Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failurePublication . Theys, Kristof; Abecasis, Ana; Libina, Pieter; Gomes, Perpétua; Cabanas, Joaquim; Camacho, Ricardo J.; Van Laethem, KristelBACKGROUND: 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.
- Donor-Recipient identification in para- and poly-phyletic trees under alternative HIV-1 transmission hypotheses using approximate Bayesian computationPublication . Romero-Severson, Ethan O.; Bulla, Ingo; Hengartner, Nick; Bártolo, Inês; Abecasis, Ana; Azevedo-Pereira, José M.; Taveira, Nuno; Leitner, ThomasDiversity of the founding population of Human Immunodeficiency Virus Type 1 (HIV-1) transmissions raises many important biological, clinical, and epidemiological issues. In up to 40% of sexual infections, there is clear evidence for multiple founding variants, which can influence the efficacy of putative prevention methods, and the reconstruction of epidemiologic histories. To infer who-infected-whom, and to compute the probability of alternative transmission scenarios while explicitly taking phylogenetic uncertainty into account, we created an approximate Bayesian computation (ABC) method based on a set of statistics measuring phylogenetic topology, branch lengths, and genetic diversity. We applied our method to a suspected heterosexual transmission case involving three individuals, showing a complex monophyletic-paraphyletic-polyphyletic phylogenetic topology. We detected that seven phylogenetic lineages had been transmitted between two of the individuals based on the available samples, implying that many more unsampled lineages had also been transmitted. Testing whether the lineages had been transmitted at one time or over some length of time suggested that an ongoing superinfection process over several years was most likely. While one individual was found unlinked to the other two, surprisingly, when evaluating two competing epidemiological priors, the donor of the two that did infect each other was not identified by the host root-label, and was also not the primary suspect in that transmission. This highlights that it is important to take epidemiological information into account when analyzing support for one transmission hypothesis over another, as results may be nonintuitive and sensitive to details about sampling dates relative to possible infection dates. Our study provides a formal inference framework to include information on infection and sampling times, and to investigate ancestral node-label states, transmission direction, transmitted genetic diversity, and frequency of transmission.
- Emerging patterns in HIV integrase resistancePublication . Veloso, Margarida; Ribeiro, Marta; Cabanas, Joaquim; Gonçalves, Fátima; Fernandes, Sandra; Diogo, Isabel; Costa, Inês; Pimentel, Victor; Pingarilho, Marta; Abecasis, Ana; Gomes, PerpétuaWe 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.
- HIV-1 late diagnosis : strategies to overcome the misclassification of individuals acutely infected with HIV-1 as individuals diagnosed latePublication . 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 GroupObjectives: 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.
- HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019Publication . Pingarilho, Marta; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca Branco; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; da Silva, Elisabete Gomes; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltez, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José; Poças, José; da Cunha, José Saraiva; Soares, Jorge; Henriques, Júlia; Mansinho, Kamal; Pedro, Liliana; Aleixo, Maria João; Gonçalves, Maria João; Manata, Maria José; Mouro, Margarida; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo; Pinho, Raquel; Tavares, Raquel; de Abreu, Ricardo Correia; Côrte-Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Martins, Maria Rosário O.; Gomes, Perpétua; Mendão, Luís; Simões, Daniel; Abecasis, AnaObjective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.
- HIV-1-transmitted drug resistance and transmission clusters in newly diagnosed patients in Portugal between 2014 and 2019Publication . Pingarilho, Marta; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca Branco; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; Silva, Elisabete Gomes da; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltez, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José; Poças, José; Cunha, José Saraiva da; Soares, Jorge; Henriques, Júlia; Mansinho, Kamal; Pedro, Liliana; Aleixo, Maria João; Gonçalves, Maria João; Manata, Maria José; Mouro, Margarida; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo; Pinho, Raquel; Tavares, Raquel; Abreu, Ricardo Correia de; Côrte-Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Martins, Maria Rosário O.; Gomes, Perpétua; Mendão, Luís; Simões, Daniel; Abecasis, Ana; on behalf of the BESTHOPE Study GroupObjective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.
- HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimenPublication . Cavaco-Silva, Joana; Abecasis, Ana; Miranda, Ana Cláudia; Poças, José; Narciso, Jorge; Águas, Maria João; Maltez, Fernando; Almeida, Isabel; Germano, Isabel; Diniz, António; Gonçalves, Maria de Fátima; Gomes, Perpétua; Cunha, Celso; Camacho, Ricardo Jorge
- Hybrid next-generation sequencing protocol for testing HIV-2 drug resistancePublication . Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Veloso, Margarida; Ribeiro, Marta; Fernandes, Sandra; Diogo, Isabel; Sebastião, Cruz S.; Pingarilho, Marta; Pimentel, Victor; Abecasis, Ana; Gomes, PerpétuaHIV-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.