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Objective. To describe the drug resistance profile in newly HIV-1 patients. Methodology. A total of 243 newly HIV-1 diagnosed patients with no record of Antiretroviral -ART- intake were included. They all underwent HIV-1 genotype testing from January 2018 to June 2020. The analysis was performed in the DeepChek® v2.0 software. Resistance levels were classified following the Stanford HIVdb algorithm (v9.4 - 12/17/2022). Results Overall resistance to any ART family was found in 17.3% (95% CI 12.8 - 22.6%). Resistance NNRTIs was found in 13.6% (95% CI 9.5 - 18.5%), mainly affecting NVP and EFV meanwhile the NRTIs showed 1.6% (95% CI 0.5 - 4.2%), mostly in FTC/3TC. For PIs it was 4.5% (95% CI 2.3 - 8.0%), with NFV being the most affected. The most frequently found mutations were K103N in 38.1%, M46I/L and V82A in 11.9% each and M41L, K70R, M184V with 4.8% each mutation. Conclusion. The high HIV-1 resistance in newly diagnosed patients without prior ART exposure shows the close relationship between the availability of ART throughout the time in Guatemala and the acquired and transmission of HIV resistance. Therefore, timely and cost-effective actions and interventions are needed., Objetivo. Describir el perfil de resistencia primaria a la terapia antirretroviral. Metodología. Se incluyó 243 de pacientes de reciente diagnóstico de VIH-1 sin antecedente de uso de TAR, con prueba de genotipo de VIH-1, de enero del 2018 a junio del 2020. El análisis se realizó en el software DeepChek® v2.0, los niveles de resistencia se clasificaron siguiendo el algoritmo de Stanford HIVdb (v9.4 - 17/12/2022). Resultados. El 17.3% (IC 95% 12.8 - 22.6%) presentó resistencia general a alguna familia de ARVs. La resistencia por familia fue de 13.6% (IC 95% 9.5 - 18.5%) para INNTR afectando principalmente a NVP y EFV; 1.6% (IC 95% 0.5 - 4.2%) para INTR, mayormente en FTC/3TC y 4.5% (IC 95% 2.3 - 8.0%) para IP, siendo NFV el más afectado. Las mutaciones más frecuentemente encontradas fueron la K103N en 38.1%, M41L, K70R, M184V en 4.8% cada una, M46I/L y V82A en 11.9% cada mutación. Conclusión. La elevada resistencia al VIH-1 en pacientes de reciente diagnóstico sin previa exposición a TAR, evidencia la estrecha relación entre el historial de ARVs disponibles en el país, la resistencia adquirida del VIH y la transmisión de la resistencia, por lo que es necesario realizar acciones e intervenciones oportunas y costo-efectivas.

Immune checkpoint inhibitors (ICIs) have contributed significantly to the treatment of various types of cancer, including skin cancer. However, not all patients respond; some patients do not respond at all (primary resistance), while others experience recurrence after the initial response (acquired resistance). Therefore, overcoming ICI resistance is an urgent priority. Numerous ICI resistance mechanisms have been reported. They are seemingly quite complex, varying from patient to patient. However, most involve T cell activation processes, especially in the tumor microenvironment (TME). ICIs exert their effects in the TME by reactivating suppressed T cells through inhibition of immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Thus, this review focuses on the resistance mechanisms based on the T cell activation process. Here, we classify the main mechanisms of ICI resistance into three categories based on: (1) antigen recognition, (2) T cell migration and infiltration, and (3) effector functions of T cells. By identifying and understanding these resistance mechanisms individually, including unknown mechanisms, we seek to contribute to the development of novel treatments to overcome ICI resistance.

Immune checkpoint inhibitors (ICIs) have contributed significantly to the treatment of various types of cancer, including skin cancer. However, not all patients respond; some patients do not respond at all (primary resistance), while others experience recurrence after the initial response (acquired resistance). Therefore, overcoming ICI resistance is an urgent priority. Numerous ICI resistance mechanisms have been reported. They are seemingly quite complex, varying from patient to patient. However, most involve T cell activation processes, especially in the tumor microenvironment (TME). ICIs exert their effects in the TME by reactivating suppressed T cells through inhibition of immune checkpoint molecules, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Thus, this review focuses on the resistance mechanisms based on the T cell activation process. Here, we classify the main mechanisms of ICI resistance into three categories based on: (1) antigen recognition, (2) T cell migration and infiltration, and (3) effector functions of T cells. By identifying and understanding these resistance mechanisms individually, including unknown mechanisms, we seek to contribute to the development of novel treatments to overcome ICI resistance.

We evaluated the clinical and immunopathological features of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors. The rate of smoking was significantly higher in primary resistance. The immune microenvironment characterized by low total tumor infiltrating lymphocytes and negative programmed death ligand 1 correlated significantly with primary resistance. Background: Approximately 20% to 30% of nonesmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumorinfiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC. However, few studies have directly focused on the relationship between the tumor immunemicroenvironment and primary resistance to EGFR-TKIs. Materials and Methods: The characteristics of 124 NSCLC patients with EGFR mutations who had received EGFR-TKIs were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFRTKI treatment were assessed for the density of TILs expressing CD4 or CD8 and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% of the patients (17 of 124). A significant difference in smoking history was observed between patients with primary resistance and those with noneprimary resistance. A lower density of total TILs and negative PD-L1 expression on immunohistochemical analysis correlated significantly with primary resistance, in contrast to tha

We evaluated the clinical and immunopathological features of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors. The rate of smoking was significantly higher in primary resistance. The immune microenvironment characterized by low total tumor infiltrating lymphocytes and negative programmed death ligand 1 correlated significantly with primary resistance. Background: Approximately 20% to 30% of nonesmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumorinfiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC. However, few studies have directly focused on the relationship between the tumor immunemicroenvironment and primary resistance to EGFR-TKIs. Materials and Methods: The characteristics of 124 NSCLC patients with EGFR mutations who had received EGFR-TKIs were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFRTKI treatment were assessed for the density of TILs expressing CD4 or CD8 and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% of the patients (17 of 124). A significant difference in smoking history was observed between patients with primary resistance and those with noneprimary resistance. A lower density of total TILs and negative PD-L1 expression on immunohistochemical analysis correlated significantly with primary resistance, in contrast to tha

We evaluated the clinical and immunopathological features of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors. The rate of smoking was significantly higher in primary resistance. The immune microenvironment characterized by low total tumor infiltrating lymphocytes and negative programmed death ligand 1 correlated significantly with primary resistance. Background: Approximately 20% to 30% of nonesmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumorinfiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC. However, few studies have directly focused on the relationship between the tumor immunemicroenvironment and primary resistance to EGFR-TKIs. Materials and Methods: The characteristics of 124 NSCLC patients with EGFR mutations who had received EGFR-TKIs were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFRTKI treatment were assessed for the density of TILs expressing CD4 or CD8 and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% of the patients (17 of 124). A significant difference in smoking history was observed between patients with primary resistance and those with noneprimary resistance. A lower density of total TILs and negative PD-L1 expression on immunohistochemical analysis correlated significantly with primary resistance, in contrast to tha

SCOPUS: re.j, info:eu-repo/semantics/published

SCOPUS: re.j, info:eu-repo/semantics/published