RESUMO
Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.
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OBJECTIVE: Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). METHODS: Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. RESULTS: TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. CONCLUSIONS: NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Argentina , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Transmissão Vertical de Doenças Infecciosas , Mutação , Gravidez , Gestantes , Inibidores de Proteases/uso terapêutico , DNA Polimerase Dirigida por RNA/uso terapêutico , Estudos Retrospectivos , Carga ViralRESUMO
Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103â¯IU/ml (group A) orâ¯>â¯103â¯IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9â¯×â¯10-4⯱â¯1.3â¯×â¯10-4) than group B (2.7â¯×â¯10-4⯱â¯7.4â¯×â¯10-5 substitution/site/year, pâ¯<â¯.001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.
Assuntos
Evolução Molecular , Vírus da Hepatite B/genética , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Carga Viral , Adulto , DNA Viral , Feminino , Genoma Viral , Genótipo , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Mutação , Fases de Leitura Aberta , Seleção GenéticaRESUMO
BACKGROUND: In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level. OBJECTIVES: To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology. METHODS: This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm. RESULTS: Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The meanâ±âSD age was 35â±â11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N. CONCLUSIONS: This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.