Percorrer por autor "Martins, Andreia"
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- A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision supportPublication . Döring, Matthias; Borrego, Pedro; Büch, Joachim; Martins, Andreia; Friedrich, Georg; Camacho, Ricardo Jorge; Eberle, Josef; Kaiser, Rolf; Lengauer, Thomas; Taveira, Nuno; Pfeifer, NicoBackground: CCR5-coreceptor antagonists can be used for treating HIV-2 infected individuals. Before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the CCR5 coreceptor (R5) and cannot evade the drug by using the CXCR4 coreceptor (X4-capable). However, until now, no online tool for the genotypic identification of HIV-2 coreceptor usage had been available. Furthermore, there is a lack of knowledge on the determinants of HIV-2 coreceptor usage. Therefore, we developed a data-driven web service for the prediction of HIV-2 coreceptor usage from the V3 loop of the HIV-2 glycoprotein and used the tool to identify novel discriminatory features of X4-capable variants. Results: Using 10 runs of tenfold cross validation, we selected a linear support vector machine (SVM) as the model for geno2pheno[coreceptor-hiv2], because it outperformed the other SVMs with an area under the ROC curve (AUC) of 0.95. We found that SVMs were highly accurate in identifying HIV-2 coreceptor usage, attaining sensitivities of 73.5% and specificities of 96% during tenfold nested cross validation. The predictive performance of SVMs was not significantly different (p value 0.37) from an existing rules-based approach. Moreover, geno2pheno[coreceptor-hiv2] achieved a predictive accuracy of 100% and outperformed the existing approach on an independent data set containing nine new isolates with corresponding phenotypic measurements of coreceptor usage. geno2pheno[coreceptor-hiv2] could not only reproduce the established markers of CXCR4-usage, but also revealed novel markers: the substitutions 27K, 15G, and 8S were significantly predictive of CXCR4 usage. Furthermore, SVMs trained on the amino-acid sequences of the V1 and V2 loops were also quite accurate in predicting coreceptor usage (AUCs of 0.84 and 0.65, respectively). Conclusions: In this study, we developed geno2pheno[coreceptor-hiv2], the first online tool for the prediction of HIV-2 coreceptor usage from the V3 loop. Using our method, we identified novel amino-acid markers of X4-capable variants in the V3 loop and found that HIV-2 coreceptor usage is also influenced by the V1/V2 region. The tool can aid clinicians in deciding whether coreceptor antagonists such as maraviroc are a treatment option and enables epidemiological studies investigating HIV-2 coreceptor usage. geno2pheno[coreceptor-hiv2] is freely available at http://coreceptor-hiv2.geno2pheno.org.
- A helical short-peptide fusion inhibitor with highly potent activity against Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency VirusPublication . Xiong, Shengwen; Borrego, Pedro; Ding, Xiaohui; Zhu, Yuanmei; Martins, Andreia; Chong, Huihui; Taveira, Nuno; He, YuxianHuman immunodeficiency virus type 2 (HIV-2) has already spread to different regions worldwide, and currently about 1 to 2 million people have been infected, calling for new antiviral agents that are effective on both HIV-1 and HIV-2 isolates. T20 (enfuvirtide), a 36-mer peptide derived from the C-terminal heptad repeat region (CHR) of gp41, is the only clinically approved HIV-1 fusion inhibitor, but it easily induces drug resistance and is not active on HIV-2. In this study, we first demonstrated that the M-T hook structure was also vital to enhancing the binding stability and inhibitory activity of diverse CHR-based peptide inhibitors. We then designed a novel short peptide (23-mer), termed 2P23, by introducing the M-T hook structure, HIV-2 sequences, and salt bridge-forming residues. Promisingly, 2P23 was a highly stable helical peptide with high binding to the surrogate targets derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV). Consistent with this, 2P23 exhibited potent activity in inhibiting diverse subtypes of HIV-1 isolates, T20-resistant HIV-1 mutants, and a panel of primary HIV-2 isolates, HIV-2 mutants, and SIV isolates. Therefore, we conclude that 2P23 has high potential to be further developed for clinical use, and it is also an ideal tool for exploring the mechanisms of HIV-1/2- and SIV-mediated membrane fusion.
- Longitudinal analysis of HIV-2 proviral DNA reveals archived protease inhibitor resistance and reservoir evolution over eight yearsPublication . Gonçalves, Paloma; Lopes, Inês; Martins, Andreia; Maia, Filipa; Martin, Francisco; Borrego, Pedro; Antunes, Francisco; Valadas, Emília; Palladino, Claudia; Bártolo, Inês; Taveira, NunoProtease inhibitors (PIs) remain important components of HIV-2 treatment, but resistance genotyping is frequently challenging in individuals with low or undetectable plasma viremia. Proviral DNA sequencing may provide access to archived viral variants and improve understanding of long-term resistance and clinical evolution. In this retrospective longitudinal study, 27 individuals with HIV-2, both ART-experienced and ART-naïve, followed at a hospital in Lisbon, were analyzed. The HIV-2 protease gene was amplified from peripheral blood mononuclear cell-derived proviral DNA, cloned, and sequenced (Sanger sequencing) at baseline and, for ART-treated participants, after eight years of follow-up. Resistance profiles were interpreted using the Stanford HIVdb, HIV-2EU, and Rega algorithms. Clinical data, including ART history, CD4 counts, and plasma viral load, were collected longitudinally. Amino acid diversity was assessed using Shannon entropy, and longitudinal CD4 dynamics were evaluated using mixed-effects models with time-varying ART exposure. Sensitivity analyses were performed using generalized estimating equations (GEE). A total of 222 clonal HIV-2 protease sequences clustered within group A. Major PI resistance mutations were detected in 21.4% of ART-experienced and 23.1% of ART-naïve individuals at baseline. Longitudinal resistance trajectories varied across participants, including persistence, apparent emergence, and non-detection of previously identified mutations. Mixed-effects modeling revealed substantial inter-individual variability in CD4 trajectories, with no statistically significant associations observed between CD4 evolution and ART status, time, or their interaction. GEE analyses yielded consistent results, supporting robustness across modeling frameworks. Entropy analysis identified localized sequence diversity changes restricted to a small number of protease residues, with positions 60 and 75 differing between groups at baseline and position 21 showing longitudinal variation among treated participants. This study demonstrates that proviral DNA sequencing captures archived HIV-2 protease diversity and reveals persistent and dynamic resistance patterns within the viral reservoir. While no population-level association between ART exposure and CD4 trajectory was observed, marked inter-individual variability highlights the complexity of longitudinal immune recovery in HIV-2 infection. These findings support the value of proviral sequencing as a complementary research tool for characterizing long-term viral evolution in settings where plasma-based genotyping is limited.
- A nova ordem nuclearPublication . Martins, Andreia; Eugénio, António Luís Beja; Gonçalves, Bruno Soares; Rodrigues, Eurico; Galamas, Francisco; Garcia, Francisco Proença; Correia, João; Cunha, Luís; Magalhães, Nuno Pereira deO IDN Brief que agora se publica, dedicado ao tema “A Nova Ordem Nuclear” oferece uma visão panorâmica e atual da problemática nuclear nas suas vertentes civil e militar. Conta, para o efeito, com um qualificado conjunto de artigos assinados por académicos e especialistas. Com esta publicação esperamos contribuir para a discussão de um tema que voltou a estar no centro das relações internacionais