Percorrer por autor "Antunes, Francisco"
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- Baseline susceptibility of primary HIV-2 to entry inhibitorsPublication . Borrego, Pedro; Calado, Rita; Marcelino, José M; Bártolo, Inês; Rocha, Cheila; Cavaco-Silva, Patrícia; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Caixas, Umbelina; Barroso, Helena; Taveira, NunoBackground: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown.
- Development of Nevirapine resistance in children exposed to the prevention of mother-to-child HIV-1 transmission programme in Maputo, MozambiquePublication . Antunes, Francisco; Zindoga, Pereira; Gomes, Perpétua; Augusto, Orvalho; Mahumane, Isabel; Veloso, Luís; Valadas, Emília; Camacho, Ricardo"Background: single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. Objectives: to assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique."
- Hepatitis C antibody prevalence and behavioral correlates in people who inject drugs attending harm reduction services in Lisbon, PortugalPublication . Curado, Adriana; Nogueira, Paulo Jorge; Virgolino, Ana; Santa Maria, João; Mendão, Luís; Furtado, Cristina; Antunes, FranciscoThe hepatitis C virus (HCV) infection is an important public health problem, affecting millions of people worldwide. People who inject drugs (PWID) are at increased risk of HCV infection due to, among other factors, widespread unsafe injecting practices, such as sharing of infected equipment or unprotected sexual practices. In Portugal, there is a lack of data regarding the proportion of infected persons through injecting drug use. This study aimed to evaluate the anti-HCV prevalence and behavioral correlates of infection in PWID attending harm reduction services in the Metropolitan Area of Lisbon, Portugal. A cross-sectional study with a purposive sample of PWID was undertaken between March 2018 and March 2020. Participants were recruited through the harm-reduction services of a nongovernmental organization. A rapid diagnostic test for anti-HCV screening was performed. Data on drug consumption history and current practices, past HCV testing, care and treatment history, and knowledge regarding hepatitis C were also collected through a questionnaire applied by trained inquirers. A total of 176 PWID participated in this study. An overall prevalence of 70.5% of anti-HCV positive in this population was found. Those with an anti-HCV positive testing result tended to start consuming at a younger age and have a higher consumption of benzodiazepines in the last 30 days. Sharing needles and other injecting material is a frequent risk behavior among this group. Also, they are more likely to have attended an opioid agonist treatment and to have undertaken previous hepatitis C and HIV tests in the past. This study represents an important effort to better understand the HCV prevalence and behavioral correlates of infection among PWID in Portugal, as well as to better estimate those in need of HCV treatment.
- 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.
- Population approach to Efavirenz therapyPublication . Duarte, Hélder; Cruz, João Paulo; Aniceto, Natália; Ribeiro, Ana Clara; Fernandes, Ana; Paixão, Paulo; Antunes, Francisco; Morais, JoséEfavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor commonly used as first-line therapy in the treatment of human immunodeficiency virus (HIV), with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady-state plasma concentrations, a population pharmacokinetic model was developed from 96 HIV-positive individuals, using a nonlinear mixed-effect method with Monolix® software. A one-compartment with first-order absorption and elimination model adequately described the data. To explain between-subject variability, demographic characteristics, biochemical parameters, hepatitis C virus–HIV coinfection, and genetic polymorphisms were tested. A combination of the single-nucleotide polymorphisms rs2279343 and rs3745274, both in the CYP2B6 gene, were the only covariates influencing clearance, included in the final model. Oral clearance was estimated to be 19.6 L/h, 14.15 L/h, and 6.08 L/h for wild-type, heterozygous mutated and homozygous mutated individuals, respectively. These results are in accordance with the current knowledge of EFV metabolism and also suggest that in homozygous mutated individuals, a dose adjustment is necessary. Hepatitis C virus–HIV coinfection does not seem to be a predictive indicator of EFV pharmacokinetic disposition.
- Resistance to antibody neutralization in HIV-2 infection occurs in late stage disease and is associated with X4 tropismPublication . Marcelino, José Maria; Borrego, Pedro; Nilsson, Charlotta; Família, Carlos; Barroso, Helena; Maltez, Fernando; Doroana, Manuela; Antunes, Francisco; Quintas, Alexandre; Taveira, NunoObjectives: To characterize the nature and dynamics of the neutralizing antibody (NAb) response and escape in chronically HIV-2 infected patients.