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1.
Early Hum Dev ; 194: 106050, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38781715

ABSTRACT

BACKGROUND: Our objective was to determine whether the use of two or more courses of low-dose systemic dexamethasone for extubation of ventilator-dependent preterm infants after the first week of life, as proposed in the DART study, is associated with greater neurodevelopmental harm at two years of corrected age, compared to a single course. METHODS: Retrospective review at seven level III neonatal intensive care units. Preterm infants who underwent only one course of systemic dexamethasone for extubation were grouped into DART-1; those who underwent two or more courses were grouped into DART-2. Data and outcomes of infants in DART-2 were compared with those in DART-1. RESULTS: 150 preterm infants were studied: 104 in DART-1 and 46 in DART-2. Patients in DART-2 had a lower gestational age (25 vs. 26 weeks, p = 0.031) and greater morbidity. The average dexamethasone cumulative dose for patients in DART-1 was 0.819 mg/kg, vs. 1.697 mg/kg for patients in DART-2. A total of 14 patients died. The neuromotor and neurosensory assessments at two years of corrected age revealed in the DART-2 survivors, after the multivariate analysis, a higher prevalence of cerebral palsy with functional motor class 2 (OR = 6.837; 95%CI: 1.054-44.337; p = 0.044) and ophthalmological problems requiring the use of glasses (OR = 4.157; 95%CI: 1.026-16.837; p = 0.046). CONCLUSIONS: In this cohort, the use of more than one course of systemic dexamethasone in low doses for extubation of ventilator-dependent premature infants after the first week of life was associated, at two years of corrected age, with a higher prevalence of cerebral palsy with functional motor class 2 and ophthalmological problems requiring the use of glasses.


Subject(s)
Cerebral Palsy , Dexamethasone , Infant, Premature , Humans , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Cerebral Palsy/epidemiology , Infant, Newborn , Female , Male , Retrospective Studies , Child, Preschool , Prevalence , Airway Extubation , Respiration, Artificial
2.
Viruses ; 16(4)2024 04 17.
Article in English | MEDLINE | ID: mdl-38675962

ABSTRACT

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).


Subject(s)
Anti-HIV Agents , Drug Resistance, Viral , HIV Infections , HIV-1 , High-Throughput Nucleotide Sequencing , Mutation , Humans , HIV-1/genetics , HIV-1/drug effects , Portugal/epidemiology , HIV Infections/virology , HIV Infections/drug therapy , HIV Infections/epidemiology , Drug Resistance, Viral/genetics , Male , Female , Middle Aged , Adult , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Genotype , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Young Adult , Aged
3.
Clin Infect Dis ; 76(9): 1628-1635, 2023 05 03.
Article in English | MEDLINE | ID: mdl-36571282

ABSTRACT

BACKGROUND: We evaluated the prevalence of transmitted drug resistance (TDR) to integrase strand-transfer inhibitors (INSTIs) and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and of clinically relevant resistance (CRR) in newly diagnosed people with human immunodeficiency virus (HIV; PWH) naive to antiretroviral therapy (ART) in Europe. METHODS: MeditRes is a consortium that includes ART-naive PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during 2018-2021. Reverse transcriptase and INSTI sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM), we used the calibrated population resistance tools from the Stanford HIV website. To evaluate CRR, defined as any resistance level ≥3, we used the Stanford HIV Drug Resistance Database v.9.1 algorithm. RESULTS: We included 2705 PWH, 72% men, median age of 37 years (interquartile range, 30-48); 43.7% were infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G, R263K; all n=1) and the prevalence of NRTI-SDRMs was 5.77% (M184V: 0.85%; M184I: 0.18%; K65R/N: 0.11%; K70E: 0.07%; L74V/I: 0.18%; any thymidine analog mutations: 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir, 2.29% raltegravir/elvitegravir) and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide, 1.74% abacavir, 1.07% lamivudine/emtricitabine). CONCLUSIONS: We present the most recent data on TDR to integrase-based first-line regimens in Europe. Given the low prevalence of CRR to second-generation integrase inhibitors and to first-line NRTIs during 2018-2021, it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second-generation integrase inhibitors.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , HIV Integrase , HIV-1 , Male , Humans , Adult , Female , Integrases/genetics , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Mutation , Europe/epidemiology , HIV-1/genetics , Adenine , Drug Resistance, Viral/genetics , HIV Integrase/genetics , Heterocyclic Compounds, 3-Ring/therapeutic use
4.
AIDS ; 36(7): 997-1005, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35220350

ABSTRACT

OBJECTIVE: To investigate the dynamics of phylogenetic transmission clusters involving immigrants of Portuguese Speaking Countries living in Portugal. DESIGN/METHODS: We included genomic sequences, sociodemographic and clinical data from 772 HIV migrants followed in Portugal between 2001 and 2017. To reconstruct HIV-1 transmission clusters, we applied phylogenetic inference from 16 454 patients: 772 migrants, 2973 Portuguese and 12 709 global controls linked to demographic and clinical data. Transmission clusters were defined using: clusters with SH greater than 90% (phylogenetic support), genetic distance less than 3.5% and clusters that included greater than 66% of patients from one specific geographic origin compared with the total of sequences within the cluster. Logistic regression was performed to assess factors associated with clustering. RESULTS: Three hundred and six (39.6%) of migrants were included in transmission clusters. This proportion differed substantially by region of origin [Brazil 54% vs. Portuguese Speaking African Countries (PALOPs) 36%, P < 0.0001] and HIV-1 infecting subtype (B 52%, 43% subtype G and 32% CRF02_AG, P < 0.001). Belonging to a transmission cluster was independently associated with treatment-naive patients, CD4+ greater than 500, with recent calendar years of sampling, origin from PALOPs and with seroconversion. Among Brazilian migrants - mainly infected with subtype B - 40.6% were infected by Portuguese. Among migrants from PALOPs - mainly infected with subtypes G and CFR02_AG - the transmission occurred predominantly within the migrants' community (53 and 80%, respectively). CONCLUSION: The acquisition of infection among immigrants living in Portugal differs according to the country of origin. These results can contribute to monitor the HIV epidemic and prevent new HIV infections among migrants.


Subject(s)
Emigrants and Immigrants , HIV Infections , HIV-1 , HIV Infections/epidemiology , HIV-1/genetics , Humans , Phylogeny , Portugal/epidemiology
5.
AIDS Res Ther ; 18(1): 69, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34641890

ABSTRACT

BACKGROUND: The current standard of care is to start antiretroviral therapy in all patients diagnosed with HIV-1, as for HIV-2 current DHHS guideline suggests ART for HIV-2 as soon as diagnosis is established, although this practice is not universal, for instance, in Portugal there are specific criteria to start treatment. CASE PRESENTATION: We present a case of a man, chronically infected with HIV-1, HIV-2 and hepatitis B virus who developed resistance to HIV-2 while maintaining HIV-1 under control. 6 years after starting antiretroviral therapy he had his first virologic failure. We performed HIV-2 resistance tests that revealed high-grade resistance to all nucleoside reverse-transcriptase inhibitors except tenofovir and to all protease inhibitors except darunavir. After a decade of permanent poor adherence to therapy he developed resistance to both tenofovir and darunavir. We put together a new regiment with tenofovir alafenamide + emtricitabine + dolutegravir + maraviroc and nowadays he is with undetectable HIV-1 and HIV-2 viral loads. CONCLUSIONS: This shows the importance of having access to HIV-2 viral load determination and HIV-2 resistance testing.


Subject(s)
Coinfection , HIV Infections , HIV-1 , Coinfection/drug therapy , HIV Infections/drug therapy , HIV-1/genetics , HIV-2/genetics , Hepatitis B virus/genetics , Humans , Male
6.
Viruses ; 12(11)2020 10 30.
Article in English | MEDLINE | ID: mdl-33143301

ABSTRACT

INTRODUCTION: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). OBJECTIVE: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. METHODS: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. RESULTS AND DISCUSSION: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). CONCLUSIONS: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/epidemiology , HIV Infections/transmission , HIV-1/drug effects , Adolescent , Adult , Anti-HIV Agents/pharmacology , Female , Genotype , HIV Infections/drug therapy , HIV-1/genetics , Humans , Male , Middle Aged , Mutation , Phylogeny , Portugal/epidemiology , Prevalence , Public Health/methods , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Young Adult
7.
Viruses ; 12(3)2020 02 28.
Article in English | MEDLINE | ID: mdl-32121161

ABSTRACT

Migration is associated with HIV-1 vulnerability. OBJECTIVES: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. RESULTS: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. CONCLUSIONS: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.


Subject(s)
Genotype , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/genetics , Transients and Migrants , Adult , Anti-Retroviral Agents/pharmacology , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , Female , HIV Infections/drug therapy , HIV Infections/history , HIV-1/drug effects , History, 21st Century , Humans , Male , Middle Aged , Molecular Epidemiology , Portugal/epidemiology , Portugal/ethnology , Public Health Surveillance , RNA, Viral , Viral Load , pol Gene Products, Human Immunodeficiency Virus
9.
Mol Clin Oncol ; 9(4): 459-463, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30233798

ABSTRACT

The aim of this study was to estimate the prevalence of suspected head and neck cancer (HNC) diagnoses made by otolaryngologists in a population with subsequently confirmed cancer diagnoses in Germany. This study included patients with an initial documentation of confirmed cancer diagnosis made in 137 otolaryngology practices between January 2012 and December 2016 (index date). The main outcome of the study was the prevalence of diagnoses of suspected cancer in otolaryngology practices within one year prior to the first documentation of a confirmed cancer diagnosis. The association between the defined demographic and clinical variables with diagnoses of suspected cancer was analyzed using a logistic regression model. A total of 6,446 patients received a confirmed cancer diagnosis. A total of 23.1% of the population received a diagnosis of suspected cancer within 12 months prior to the first documentation of a confirmed cancer diagnosis. Patients over the age of 50 (ORs ranging from 1.44 to 1.55) and men (OR=1.52) were more likely to receive a diagnosis of suspected cancer compared with patients aged 50 or under and women. Cancer of the pyriform sinus (OR=3.00) and cancer of the thyroid gland (OR=0.27) were associated with increased and decreased odds of a diagnosis of suspected cancer compared to laryngeal cancer respectively. Overall, approximately 23% of individuals received a diagnosis of suspected cancer within a year prior to the first documentation of confirmed HNC.

10.
Viruses ; 10(5)2018 04 26.
Article in English | MEDLINE | ID: mdl-29701642

ABSTRACT

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).


Subject(s)
Antiviral Agents/therapeutic use , Drug Resistance, Viral/genetics , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/virology , Viral Nonstructural Proteins/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Benzimidazoles/therapeutic use , Cohort Studies , Female , Fluorenes/therapeutic use , Genotype , Hepacivirus/drug effects , Hepatitis C/epidemiology , Hepatitis C/genetics , Humans , Male , Middle Aged , Portugal/epidemiology , Prevalence , RNA, Viral/genetics , Sofosbuvir , Treatment Failure , Uridine Monophosphate/analogs & derivatives , Uridine Monophosphate/therapeutic use
12.
J Virol Methods ; 193(1): 18-22, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23692686

ABSTRACT

Quantitation of HIV-1 RNA levels in plasma has significant prognostic value since high viral load concentrations in plasma are associated with a faster disease progression. Viral load testing became one the most important tools for monitoring HIV patients. New real time methodologies to quantify HIV viral load had arisen in the last decade. HIV is a virus with a high genetic variability, with the potential to negatively affect the performance of the viral load assays. Consequently, any new assay should be challenged against, at least, the most prevalent HIV-1 genetic variants. In the present study, the new version of NucliSENS EasyQ(®) HIV-1 (Version 2.0) quantitative assay was compared with another ultra-sensitive test--Abbott RealTime HIV-1--using 175 plasma samples from patients infected with several HIV-1 subtypes and recombinant forms: subtype B (41, 23%), subtype C (19, 11%), subtype G (76, 44%), and CRF02_AG (39, 22%). Overall, there was agreement between the assays in 95.43% of the samples. Both assays have a very good dynamic range [1.4-6.9] and [1.60-7.0] log10 copies/mL and excellent correlation in samples with various subtypes. Based on the fact that no clinically significant differences were observed in the viral load measurements by these two assays, HIV-1 subtypes are quantified equally by both assays. However due to HIV diversity, mainly in regions were non B subtypes are predominant more evaluations are needed, so we do not recommend to switch platform during longitudinal viral load monitoring.


Subject(s)
HIV Infections/virology , HIV-1/isolation & purification , Molecular Diagnostic Techniques/methods , Plasma/virology , RNA, Viral/isolation & purification , Viral Load/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Female , HIV-1/genetics , Humans , Infant , Male , Middle Aged , RNA, Viral/genetics , Young Adult
13.
AIDS Res Hum Retroviruses ; 27(7): 803-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21198411

ABSTRACT

The advent of new therapeutic approaches targeting env and the search for efficient anti-HIV-1 vaccines make it necessary to identify the number of recombinant forms using genomic regions that were previously not frequently sequenced. In this study, we have subtyped paired pol and env sequences from HIV-1 strains infecting 152 patients being clinically followed in Portugal. The percentage of strains in which we found discordant subtypes in pol and env was 25.7%. When the subtype in pol and env was concordant (65.1%), the most prevalent subtypes were subtype B (40.8%), followed by subtype C (17.8%) and subtype G (5.3%). The most prevalent recombinant form was CRF14_BGpol/Genv (7.2%).


Subject(s)
HIV Infections/epidemiology , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , env Gene Products, Human Immunodeficiency Virus/genetics , pol Gene Products, Human Immunodeficiency Virus/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Cluster Analysis , Female , Genotype , HIV-1/isolation & purification , Humans , Infant , Infant, Newborn , Male , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Portugal/epidemiology , Sequence Analysis, DNA , Young Adult
14.
J Virol Methods ; 135(2): 223-8, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16675034

ABSTRACT

Quantitation of HIV-1 RNA levels in plasma has an undisputed prognostic value and is extremely important for evaluating response to antiretroviral therapy. The purpose of this study was to evaluate the performance of the real-time PCR COBAS TaqMan 48 analyser, comparing it to the existing VERSANT 3.0 (bDNA) for HIV-1 RNA quantitation in plasma of individuals infected with different HIV-1 subtypes (104 blood samples). A positive linear correlation between the two tests (r2 = 0.88) was found. Quantitation by the COBAS TaqMan assay was approximately 0.32log10 higher than by bDNA. The relationship between the two assays was similar within all subtypes with a Deming regression of <1 and <0 for the Bland-Altman plots. Overall, no significant differences were found in plasma viral load quantitation in different HIV-1 subtypes between both assays; therefore these assays are suitable for viral load quantitation of highly genetically diverse HIV-1 plasma samples.


Subject(s)
HIV-1/isolation & purification , Polymerase Chain Reaction/methods , RNA, Viral/blood , HIV-1/classification , HIV-1/genetics , Humans , Viral Load
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