RESUMEN
Despite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after T cell receptor (TCR)-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular nicotinamide adenine dinucleotide and nicotinamide mononucleotide concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the oxygen consumption rate/extracellular acidification rate ratio upon TCR signaling and to increase cycling, proliferation, survival, and CD40L induction. Pharmacological inhibition of ecto-CD38 catalytic activity in TM cells from chronic HIV-infected patients rescued TCR-triggered responses, including differentiation and effector functions, while reverting abnormally increased basal glycolysis, cycling, and spontaneous proinflammatory cytokine production. Additionally, ecto-CD38 blockage normalized basal and TCR-induced mitochondrial morphofunctionality, while increasing respiratory capacity in cells from HIV+ patients and healthy individuals. Ectoenzyme CD38's immunometabolic restriction of TCR-involving stimulation is relevant to CD4T cell biology and to the deleterious effects of CD38 overexpression in HIV disease.
Asunto(s)
ADP-Ribosil Ciclasa 1 , Linfocitos T CD4-Positivos , Infecciones por VIH , Humanos , ADP-Ribosil Ciclasa 1/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Jurkat , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Glicoproteínas de Membrana/metabolismo , Glucólisis , Mitocondrias/metabolismoRESUMEN
Abstract: Objective: To determine the prevalence and risk factors for oral high-risk human papillomavirus (HR-HPV) infection in human immunodeficiency virus(HIV)-infected men. Materials and methods: Consecutive male outpatients with HIV-infection were enrolled. Demographic and behavioral risk data were obtained. Anal swabs and oral rinses were tested for HR-HPV DNA. Oral, pharyngeal and video laryngoscopy examinations were performed for detection of lesions. Results: The prevalence of HR-HPV oral infection was 9.3% (subtypes other than HR HPV 16/18 predominated). The prevalence of anal HR-HPV infection was 75.7%. The risk factors for oral infection with HR-HPV were tonsillectomy (OR=13.12) and years from HIV diagnosis (OR=1.17). Conclusions: Tonsillectomy and years from HIV diagnosis were associated with oral HPV infection. No association was found between oral and anal HR-HPV infections. This is the first study reporting the prevalence and risk factors for oral HR-HPV infection in Mexican HIV-infected population.
Resumen: Objetivo: Determinar la prevalencia y los factores de riesgo para infección oral por virus de papiloma humano de alto riesgo (VPH-AR) en individuos con VIH. Material y métodos: Se incluyeron pacientes ambulatorios consecutivos con VIH. Se recabó información demográfica y sobre factores de riesgo conductuales. Se detectó DNA de VPH-AR en hisopado rectal y enjuague bucal. Se efectuó exploración de boca, faringe y videolaringoscopía para detectar lesiones. Resultados: La prevalencia de VPH-AR oral fue 9.3% (predominaron subtipos diferentes de VPH-AR 16/18). La prevalencia de VPH-AR anal fue 75.7%. Los factores de riesgo para VPH-AR oral fueron la tonsilectomía (OR=13.12) y los años de diagnóstico del VIH (OR=1.17). Conclusiones: La tonsilectomía y los años de diagnóstico del VIH se asociaron con VPH-AR oral. No hubo asociación entre VPH-AR oral y anal. Este es el primer reporte sobre prevalencia y factores de riesgo para VPH-AR oral en población mexicana con VIH.
Asunto(s)
Humanos , Masculino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Enfermedades Faríngeas/epidemiología , Infecciones por VIH/epidemiología , Infecciones por Papillomavirus/epidemiología , Enfermedades de la Boca/epidemiología , Enfermedades del Ano/epidemiología , Papiloma/virología , Conducta Sexual , Consumo de Bebidas Alcohólicas/epidemiología , Neoplasias de la Boca/epidemiología , Fumar/epidemiología , Comorbilidad , Infecciones por VIH/sangre , Estudios Transversales , Estudios Prospectivos , Encuestas y Cuestionarios , Recuento de Linfocito CD4 , México/epidemiologíaRESUMEN
OBJECTIVE: To determine the prevalence and risk factors for oral high-risk human papillomavirus (HR-HPV) infec- tion in human immunodeficiency virus(HIV)-infected men. MATERIALS AND METHODS: Consecutive male outpatients with HIV-infection were enrolled. Demographic and behav- ioral risk data were obtained. Anal swabs and oral rinses were tested for HR-HPV DNA. Oral, pharyngeal and video laryngoscopy examinations were performed for detection of lesions. RESULTS: The prevalence of HR-HPV oral infection was 9.3% (subtypes other than HR HPV 16/18 predominated). The prevalence of anal HR-HPV infection was 75.7%. The risk factors for oral infection with HR-HPV were tonsillectomy (OR=13.12) and years from HIV diagnosis (OR=1.17). CONCLUSIONS: Tonsillectomy and years from HIV diagnosis were associated with oral HPV infection. No association was found between oral and anal HR-HPV infections. This is the first study reporting the prevalence and risk factors for oral HR-HPV infection in Mexican HIV-infected population.
OBJETIVO: Determinar la prevalencia y los factores de riesgo para infección oral por virus de papiloma humano de alto ries- go (VPH-AR) en individuos con VIH. MATERIAL Y MÉTODOS: Se incluyeron pacientes ambulatorios consecutivos con VIH. Se recabó información demográfica y sobre factores de riesgo conductuales. Se detectó DNA de VPH-AR en hisopado rectal y enjuague bucal. Se efectuó exploración de boca, faringe y videolaringoscopía para detectar lesiones. RESULTADOS: La prevalencia de VPH-AR oral fue 9.3% (predominaron subtipos diferentes de VPH-AR 16/18). La prevalencia de VPH-AR anal fue 75.7%. Los factores de riesgo para VPH-AR oral fueron la tonsilectomía (OR=13.12) y los años de diagnóstico del VIH (OR=1.17). CONCLUSIONES: La tonsilectomía y los años de diagnóstico del VIH se asociaron con VPH-AR oral. No hubo asociación entre VPH-AR oral y anal. Este es el primer reporte sobre prevalencia y factores de riesgo para VPH-AR oral en población mexicana con VIH.
Asunto(s)
Infecciones por VIH/epidemiología , Enfermedades de la Boca/epidemiología , Infecciones por Papillomavirus/epidemiología , Enfermedades Faríngeas/epidemiología , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Enfermedades del Ano/epidemiología , Enfermedades del Ano/virología , Recuento de Linfocito CD4 , Comorbilidad , Estudios Transversales , Infecciones por VIH/sangre , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Enfermedades de la Boca/virología , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/virología , Papiloma/epidemiología , Papiloma/virología , Enfermedades Faríngeas/virología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Asunción de Riesgos , Conducta Sexual , Fumar/epidemiología , Encuestas y Cuestionarios , Tonsilectomía/estadística & datos numéricos , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To describe the clinical course of infection by 2009 (H1N1) influenza virus in different stages of HIV disease. DESIGN: Prospective, observational study. METHODS: During the pandemic period, HIV-infected patients presenting respiratory symptoms at a third level referral hospital in Mexico City were tested for 2009 influenza A (H1N1) viral RNA. Clinical files were prospectively analyzed. RESULTS: Infection by H1N1 was confirmed in 30 (23.8%) of the total 126 HIV-infected patients studied. In the group of patients with 2009 H1N1 virus infection, 16 (53.3%) were hospitalized, 12 (40%) had active opportunistic infections and six (20%) died. In the group of 96 patients not infected with 2009 H1N1 virus, 54 (56.25%) were hospitalized with opportunistic infections and 12 (12.5%) died. For all hospitalized patients, being on HAART and having undetectable HIV viral loads at hospitalization was associated with higher survival (P = 0.019). Patients with 2009 H1N1 virus infection had a higher mortality rate, even after adjusting for HAART (P = 0.043). Coinfection by HIV and H1N1 2009 virus was more severe in patients with opportunistic infections, as shown by longer hospital stays (P = 0.0013), higher rates of hospitalization (P < 0.0001), use of mechanical ventilation (P = 0.0086) and death (P = 0.026). Delayed administration of oseltamivir in hospitalized patients was significantly associated with mortality (P = 0.0022). CONCLUSION: Our data suggest that infection by 2009 H1N1 is more severe in HIV-infected patients with late and advanced HIV disease than in well controlled patients under HAART.