Browsing by Author "Gallart, Teresa"
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Item Avances en el diagnóstico y tratamiento de la infección aguda por el VIH-1(2004) Miro, Jose M.; Sued, Omar; Plana, Marta; Pumarola, Tomas; Gallart, TeresaSegún la Organización Mundial de la Salud (OMS) cada día se infectan en el mundo unas 14.000 personas. Sin embargo, en pocos casos el diagnóstico se realizará durante la fase aguda de la infección por el virus de la inmunodeficiencia humana (VIH). La infección aguda por el VIH es el período comprendido entre la entrada del VIH en el organismo y la seroconversión completa, definida por una prueba de Western blot positiva. Este período dura aproximadamente 30 días y la mayoría de veces (40-90%) se acompaña de manifestaciones clínicas banales (fiebre, exantema, faringitis, úlceras en mucosas entre otras), de 2 semanas de duración, que se pueden confundir con otros procesos infecciosos comunitarios, entre ellos la mononucleosis infecciosa. El diagnóstico microbiológico se realiza por la ausencia de anticuerpos en plasma (prueba de análisis de inmunoabsorción ligado a enzimas [ELISA] negativa) y la presencia de una carga viral (CV) del VIH en plasma positiva (> 10.000 copias/ml). El diagnóstico de la infección aguda por el VIH es muy importante por varias razones: a) epidemiológicas, es el período con las mayores tasas de transmisión de la infección por el VIH y permite conocer el patrón de crecimiento de la epidemia y la tasa de transmisión de cepas resistentes a los antirretrovirales, que en España es del 10%; b) inmunopatológico, ya que es una oportunidad única para estudiar los mecanismos virológicos, inmunológicos, y genéticos implicados en la transmisión y patogenia de esta enfermedad; y c) terapéutico, ya que el inicio del tratamiento antirretroviral en esta fase podría modificar la historia natural de esta infección. Sin embargo, este es un tema controvertido y en la actualidad la mayoría de comités de expertos sólo recomiendan el tratamiento si se pueden incluir los pacientes en ensayos clínicos o si las manifestaciones clínicas son graves o duraderas.Item Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial(2016-12-13) Nicolás, David; Ambrosioni, Juan; Sued, Omar; Brunet, Mercé; López-Diéguez, María; Manzardo, Christian; Agüero, Fernando; Tuset, Montserrat; Plana, Montserrat; Guardo, Alberto C; Mosquera, María Mar; Muñoz-Fernández, M. Ángeles; Caballero, Miguel; Marcos, M. Ángeles; Gatell, Jose; de Lazzari, Elisa; Gallart, Teresa; Miró, José MBackground: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection. Patients and methods: Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3–0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated. Results: The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated. Conclusions: Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706).Item Primary human immunodeficiency virus type 1 infection: clinical, virological and immunological characteristics of 75 patients (1997-2003)(2006) Sued, Omar; Miro, Jose M.; Alquezar, Antonio; Claramonte, Xavier; García, Francesc; Plana, Marta; Arnedo, Montserrat; de Lazzari, Emilia; Gil, Carlos; Manzardo, Christian; Blanco, Juan L.; Martínez, Esteban; Mallolas, Josep; Joseph, Jordi; Pumarola, Tomas; Gallart, Teresa; Gatell, JoseObjectives: To describe the epidemiological and clinical characteristics and the evolution of a cohort of patients with primary HIV-1 infection from the Barcelona area. Methods: Prospective cohort study of HIV-infected patients diagnosed with primary HIV infection in a tertiary hospital in Barcelona (Spain) from 1997 through 2003. Descriptive analysis of epidemiological and clinical characteristics and effect of highly active antiretroviral treatment (HAART) on outcome. Results: A total of 75 patients were diagnosed, accounting for 2.9% of the total of newly diagnosed HIV patients during the same time period. Eighty-one percent of the patients were males and the median age was 30 years (IQR 26-38). The most frequent transmission route was homosexual (72%), followed by heterosexual (17%) and intravenous drug abuse (11%). Seventy-seven percent of patients presented symptoms, the most frequent being fever (98%), asthenia (86%), arthralgia-myalgia (65%), lymphadenopathy (55%), night sweats (48%) and rash. Sixty-five percent started HAART, although the proportion of patients that received HAART decreased from 79% during the period 1997-2000 to 49% during the period 2001-2003 (p < 0.01). After a median follow-up of 37 months (IQR 26-66), one patient died and eight cases were lost to follow-up. The patients who did not receive HAART had a higher probability of immunological or clinical deterioration during the follow-up when compared to the group that received HAART (42.3% versus 12.3%; p < 0.001). In treated patients, dyslipidemia and lipodystrophy were diagnosed in 58% and 37% of cases, respectively. Conclusions: Primary HIV-1 infection was diagnosed more frequently in homosexual males, and its clinical characteristics were similar to those observed in previous studies. HAART given during primary HIV infection was effective, but was associated with a high percentage of adverse effects.Item Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes(2015-7) Sued, Omar; Ambrosioni, Juan; David, Nicolás; Manzardo, Christian; Agüero, Fernando; Claramonte, Xavier; Plana, Montserrat; Tuset, Montserrat; Pumarola, Tomás; Gallart, Teresa; Gatell, Jose; Miro, Jose MBackground Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. Methods Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after ‘final stop’, compared between groups. Results Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). Conclusions STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials.