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1.
Artigo em Inglês | MEDLINE | ID: mdl-38346427

RESUMO

BACKGROUND: Switching to the 2-drug regimen dolutegravir/lamivudine demonstrated durable non-inferior efficacy vs continuing 3- or 4-drug tenofovir alafenamide-based regimens for maintaining virologic suppression in people with HIV-1 through Week 144 in TANGO. SETTING: 134 centers, 10 countries. METHODS: Adults with HIV-1 RNA <50 copies/mL for >6 months and no history of virologic failure were randomized to switch from stable tenofovir alafenamide-based regimens to dolutegravir/lamivudine on Day 1 (early-switch group) for 196 weeks. Those randomized to continue tenofovir alafenamide-based regimens on Day 1 who maintained virologic suppression at Week 144 switched to dolutegravir/lamivudine at Week 148 (late-switch group). Efficacy, safety, and tolerability (including weight and biomarker changes) of dolutegravir/lamivudine in early-switch and late-switch groups were assessed through Week 196. RESULTS: Overall, 369 participants switched to dolutegravir/lamivudine on Day 1 (early-switch) and 298 switched at Week 148 (late-switch). In the early-switch group, 83% (306/369) maintained virologic suppression through Year 4, and 3% (11/369) reported new adverse events between Weeks 144 and 196. The late-switch group at Week 196 and early-switch group at Week 48 had comparable proportions with virologic suppression (93% each) and similar safety profiles. No late-switch participants and 1 early-switch participant met confirmed virologic withdrawal criteria through Week 196, with no resistance-associated mutations observed. Treatment continued to be well tolerated long-term. CONCLUSION: Switching from tenofovir alafenamide-based regimens to dolutegravir/lamivudine showed durable efficacy, high barrier to resistance, and good tolerability through 4 years. These results support dolutegravir/lamivudine as a robust treatment for maintaining virologic suppression.

3.
J Clin Invest ; 134(8)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376918

RESUMO

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , Leucócitos Mononucleares , Provírus/genética , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico
4.
J Med Virol ; 95(12): e29287, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38084763

RESUMO

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Filogenia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Integrases/genética , Integrases/uso terapêutico , Mutação , Farmacorresistência Viral/genética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Prevalência
7.
EBioMedicine ; 95: 104773, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37639938

RESUMO

BACKGROUND: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. METHODS: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. FINDINGS: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03-2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57-6.07). Additionally, low CD4 count at cut-offs of <500 cells/µL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/µL, a CD8 count ≥1500 cells/µL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. INTERPRETATION: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/µL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. FUNDING: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, "A way to make Europe", ICI20/00058.


Assuntos
Síndrome de Imunodeficiência Adquirida , Humanos , Masculino , Feminino , Relação CD4-CD8 , Contagem de Linfócito CD4 , Europa (Continente) , Linfócitos T CD8-Positivos
8.
Expert Rev Anti Infect Ther ; 21(1): 65-76, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36399521

RESUMO

INTRODUCTION: Current recommended antiretroviral regimens include a combination of two (dual; DT) or three (triple; TT) antiretroviral drugs. This study aims to determine whether the quality of evidence from clinical trials of dolutegravir (dolutegravir/lamivudine [DTG/3TC] or dolutegravir/rilpivirine [DTG/RPV]) is methodologically comparable to that of clinical trials conducted with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). AREAS COVERED: A systematic review of the medical literature was carried out in PubMed without date or language restrictions, following the PRISMA guidelines. All aspects of the methodological design of phase 3 randomized clinical trials (RCTs) of DT and TT, evaluated by the European Medicines Agency (registration trials), were reviewed. The quality of clinical trials was assessed using the Jadad scale. EXPERT OPINION: The search identified 5, 3 and 2 phase 3 RCTs with BIC/FTC/TAF, DTG/3TC and DTG/RPV, respectively, that met the inclusion criteria. The designs would not be comparable due to differences in pre-randomization losses, blinding, patient recruitment, as well as differences in methodological quality, with the average score of the RCTs conducted with BIC/FTC/TAF, DTG/3TC and DTG/RPV being 4.2 (high quality), 3.0 (medium quality) and 3.0 (medium quality), respectively. Due to methodological differences between the BIC/FTC/TAF, DTG/3TC and DTG/RPV RCTs, the results of these are not comparable.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Adenina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico
9.
Clin Infect Dis ; 76(6): 977-985, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36345912

RESUMO

BACKGROUND: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). METHODS: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. RESULTS: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). CONCLUSIONS: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.


Assuntos
Infecções por HIV , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Masculino , Estudo de Associação Genômica Ampla , Obesidade/complicações , Aumento de Peso/genética , Infecções por HIV/complicações , Antirretrovirais/uso terapêutico
10.
BMC Infect Dis ; 22(1): 379, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428209

RESUMO

BACKGROUND: To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or advanced presenters (CD4 count < 200/µL or AIDS event at enrolment). METHODS: We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time. RESULTS: Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status. CONCLUSIONS: A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Estudos de Coortes , Infecções por HIV/epidemiologia , Humanos , Morbidade
11.
Drug Des Devel Ther ; 16: 827-841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370401

RESUMO

The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.


Assuntos
Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , SARS-CoV-2 , Replicação Viral
12.
Aging (Albany NY) ; 14(4): 1597-1610, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172279

RESUMO

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.


Assuntos
Antígenos de Neoplasias/sangue , COVID-19/sangue , Moléculas de Adesão Celular/sangue , Antígenos de Neoplasias/análise , Biomarcadores/sangue , Moléculas de Adesão Celular/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Escarro/química
13.
J Acquir Immune Defic Syndr ; 90(1): 62-68, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35090156

RESUMO

OBJECTIVES: The aims of this study were to describe patients' experiences after single-tablet regimen (STR) desimplification and its impact on self-reported treatment adherence and quality of life. METHODS: We performed a survey among all patients from the multicenter cohort of the Spanish HIV/AIDS Network who had desimplified the STRs dolutegravir/abacavir/lamivudine (DGT/ABC/3TC) or rilpivirine/tenofovir disoproxil fumarate/emtricitabine to their separate components (DTG + generic ABC/3TC or RPV + generic TDF/FTC) between December 2016 and November 2018. RESULTS: Among 216 patients who fulfilled inclusion criteria, 138 (63.9%) completed the questionnaire. Most of the patients (78.3%) knew what generic drugs are, only 8.7% believed that treatment with 2 pills is less effective than treatment with an STR, and 67.4% agreed that it is reasonable to take 2 pills instead of 1 for HIV treatment to decrease costs for the health care system. After desimplification, 13.0% of the patients stated they had more secondary effects, 8.0% had forgotten one or more doses more frequently than before, and 10.9% had sometimes forgotten to take 1 pill, but not the other. A proportion of 30.4% reported not being happy to take more pills a day, and 10.1% experienced a worse quality of life after the treatment desimplification. CONCLUSIONS: After STR desimplification, most of the patients had a fair knowledge about generic antiretrovirals, and they agreed to desimplify their STR to decrease costs. Although almost a third of the respondents were not happy to take 2 pills a day, only a minority reported worse adherence or quality of life.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Qualidade de Vida , Inquéritos e Questionários , Comprimidos , Tenofovir/uso terapêutico
15.
Clin Microbiol Infect ; 27(6): 892-896, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33662544

RESUMO

OBJECTIVES: Coronavirus disease 2019 (COVID-19) survivors are reporting residual abnormalities after discharge from hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. This study aimed to describe lung function in patients recovering from COVID-19 hospitalization and to identify biomarkers in serum and induced sputum samples from these patients. METHODS: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalization. Patients' epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardized 6-minute walk test (6MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. RESULTS: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% of patients (47/100). CT was normal in 48% of patients (48/100). Lung function was normal forced expiratory volume in one second (FEV1) ≥80%, forced vital capacity (FVC) ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide (DLCO) ≥80% in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p < 0.0001) and a lower serum lactate dehydrogenase level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 cases during hospital stay. CONCLUSIONS: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Pulmão/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Prospectivos , Testes de Função Respiratória , SARS-CoV-2/isolamento & purificação , Espanha/epidemiologia , Sobreviventes , Tomografia Computadorizada por Raios X
16.
BMJ Open ; 10(11): e039951, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33191263

RESUMO

INTRODUCTION: About 25% of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) associated with a high release of pro-inflammatory cytokines such as interleukin-6 (IL-6). The aim of the SARICOR study is to demonstrate that early administration of sarilumab (an IL-6 receptor inhibitor) in hospitalised patients with COVID-19, pulmonary infiltrates and a high IL-6 or D-dimer serum level could reduce the progression of ARDS requiring high-flow nasal oxygen or mechanical ventilation (non-invasive or invasive). METHODS AND ANALYSIS: Phase II, open-label, randomised, multicentre, controlled clinical trial to study the efficacy and safety of the administration of two doses of sarilumab (200 and 400 mg) plus best available therapy (BAT) in hospitalised adults with COVID-19 presenting cytokine release syndrome. This strategy will be compared with a BAT control group. The efficacy and safety will be monitored up to 28 days postadministration. A total of 120 patients will be recruited (40 patients in each arm). ETHICS AND DISSEMINATION: The clinical trial has been approved by the Research Ethics Committee of the coordinating centre and authorised by the Spanish Agency of Medicines and Medical Products. If the hypothesis is verified, the dissemination of the results could change clinical practice by increasing early administration of sarilumab in adult patients with COVID-19 presenting cytokine release syndrome, thus reducing intensive care unit admissions. TRIAL REGISTRATION NUMBER: NCT04357860.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Adolescente , Adulto , Idoso , Betacoronavirus , COVID-19 , Ensaios Clínicos Fase II como Assunto , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19
17.
QJM ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777050

RESUMO

BACKGROUND: Asymptomatic carriers of SARS-CoV-2 can be a vehicle for transmission of the infection. This fact is of particular importance in the case of healthcare workers (HCWs). DESIGN: Cross-sectional study in HCWs in a medium size hospital in the South of Spain. METHODS: between April 15 and 25, 2020, naso and oropharyngeal PCR determination was performed together with IgG and IgM antibody determination by immunochromatography to the HCWs of the Costa del Sol Hospital in Marbella of the units involved in patient care with CoVID-19: Emergencies, Intensive Care and Anesthesia, Internal Medicine and Pneumology. Other units not directly involved in the care of these patients were offered to participate. On the day of sampling, a health questionnaire was answered, reporting symptoms on the same day and in the previous fourteen days. RESULTS: 498 HCWs were studied. Two individuals were detected with PCR for SARS-CoV-2 positive. Both were asymptomatic on the day of sampling, but one of them had had a CoVID-19 compatible picture in the previous two weeks and had positive IgG and IgM; therefore, only one subject was truly asymptomatic carrier (0.2%). 9 workers with positive IgG (1.8%) were detected. CONCLUSIONS: the prevalence of asymptomatic carriers among health workers of the services directly involved in the care of patients with CoVID-19 was very low in our center. This type of strategy can be one more tool in controlling the pandemic.

19.
J Antimicrob Chemother ; 75(5): 1294-1300, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32030406

RESUMO

OBJECTIVES: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms. RESULTS: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. CONCLUSIONS: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Algoritmos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Mutação , Prevalência , Piridonas , Espanha , Triazóis
20.
Eur J Clin Pharmacol ; 76(3): 305-318, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31865412

RESUMO

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.


Assuntos
Desprescrições , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Infecções por HIV/tratamento farmacológico , Prescrição Inadequada/prevenção & controle , Medicamentos sob Prescrição/uso terapêutico , Interações Medicamentosas , Humanos , Expectativa de Vida
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