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1.
J Antimicrob Chemother ; 79(3): 595-607, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38267266

RESUMO

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.


Assuntos
Alanina , Amidas , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Piperazinas , Piridonas , Tenofovir/análogos & derivados , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Infecções por HIV/tratamento farmacológico , Emtricitabina/uso terapêutico , Estudos Retrospectivos , Adenina/uso terapêutico , Resultado do Tratamento , Combinação de Medicamentos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , RNA
2.
J Biomed Sci ; 31(1): 80, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160510

RESUMO

BACKGROUND: Around 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC). METHODS: Transversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen. RESULTS: The median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups. CONCLUSION: LLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.


Assuntos
Senescência Celular , Infecções por HIV , HIV-1 , Ativação Linfocitária , Viremia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Feminino , Ativação Linfocitária/efeitos dos fármacos , Viremia/imunologia , Viremia/tratamento farmacológico , Senescência Celular/efeitos dos fármacos , Idoso , Adulto , Linfócitos T/imunologia
3.
Nat Commun ; 15(1): 2100, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453949

RESUMO

Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targets.


Assuntos
COVID-19 , Inflamassomos , Humanos , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , COVID-19/patologia , Inflamassomos/metabolismo , Monócitos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nucleoproteínas/metabolismo , SARS-CoV-2/metabolismo
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