Articulos científicos

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Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates
(2017-11-03) Ruiz, Maria; Salido, Jimena; Abusamra, Lorena; Ghiglione, Yanina; Cevallos, Cintia; Damilano, Gabriel; Rodriguez, Ana María; Trifone, César; Laufer, Natalia; Giavedoni, Luis D; Sued, Omar; Salomon, Horacio ; Gherardi, María Magdalena; Turk, Gabriela
As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV+-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV− donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.
RBD-specific polyclonal F(ab´)(2) fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial
(2021-04-11) Lopardo, Gustavo; Belloso, Waldo H; Nannini, Esteban; Colonna, Mariana; Sanguineti, Santiago; Zylberman, Vanesa; Muñoz, Luciana; Dobarro, Martín; Lebersztein, Gabriel; Farina, Javier; Vidiella, Gabriela; Bertetti, Anselmo; Crudo, Favio; Alzogaray, Maria Fernanda; Barcelona, Laura; Teijeiro, Ricardo; Lambert, Sandra; Scublinsky, Darío; Iacono, Marisa; Stanek, Vanina; Solari, Rubén; Cruz, Pablo; Casas, Marcelo Martín; Abusamra, Lorena; Luciardi, Héctor Lucas; Cremona, Alberto; Caruso, Diego; de Miguel, Bernardo; Lloret, Santiago Perez; Millán, Susana; Kilstein, Yael; Pereiro, Ana; Sued, Omar; Cahn, Pedro; Spatz, Linus; Goldbaum, Fernando
BACKGROUND: Passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: We conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. The primary endpoint was improvement in at least two categories in the WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: Between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). The median age was 54 years old, 65.1% were male, and 61% had moderate disease at baseline. The median time from symptom onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups regarding the primary endpoint (risk difference [95% CI]: 5.28% [-3.95; 14.50]; p = 0.15). The rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. The time to improvement in two ordinal categories or hospital discharge was 14.2 (± 0.7) days in the INM005 group and 16.3 (± 0.7) days in the placebo group, hazard ratio 1.31 (95% CI 1.0 to 1.74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6.9% in the INM005 group and 11.4% in the placebo group (risk difference [95% CI]: 0.57 [0.24 to 1.37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Although not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.
The coughing patient: TB or not TB; That is the question
(2010) Laufer, Natalia; Sued, Omar; Abusamra, Lorena; Cabrini, Mercedes; Socias, Maria E.; Sisto, Alicia; Perez, Hector; Cahn, Pedro
Tuberculosis (TB) has been declared a global emergency, increasing approximately 1% each year. There are evidences that TB is being underdiagnosed worldwide1,2. One of the reasons is the failure of healthcare workers to consider TB in the differential diagnosis of patients with respiratory symptoms. Delay in the diagnosis of TB in HIV-infected people in an important contributor to the excess morbidity and mortality 2,3. The main purpose of this prospective study was to define clinical and epidemiological characteristics that can guide physician to the rapid diagnosis of pulmonary TB in HIV patients. During 18 month (10/2004 to 04/2006), all patients attending for unscheduled visits to an Infectious Diseases Division of a public Hospital in Argentina, were asked if they present cough among their symptoms and if so they were invited to participate in the study. Patients, who signed informed consent, filled a questionnaire and their clinical records were evaluated prospectively. Chest X-Rays were classified according to the classification described by Tattevin, et al.4. Epidemiological and clinical data were compared between HIV patients with TB coinfection and those with HIV and other diagnosis. X2 and t-test were used to compare data. During the period studied, 9245 unscheduled visits were recorded, with 286 patients presenting cough. Among the patients with cough, 40 did not sign the consent. Of the remaining who agreed to participated, 35 (13%) presented a TB diagnosis (positive sputum smear and/or positive sputum or blood culture for M. tuberculosis), 211 have a non-TB diagnosis (most of them with PCP –n=51, 24%-, community acquired pneumonia –n=70, 33%-). Twenty three of the TB patients were HIV co-infected. When TB-HIV-coinfected patients were evaluated (Table 1) and compared with HIV-infected patients who have cough but non-TB diagnosis, statistical association with TB was found with: hepatomegaly (p=0.005); splenomegaly (p=0.003); night-sweats (p=0.001); weight-loss of more than 5 kg (p=0.003; duration of symptoms between 15 and 30 days (p=0.03) but not with longer time; elevate alkaline phosphatase (p=0.03); chest X-ray pattern of typical (p=0.0003) or compatible (p=0.013) with TB and previous contact with a patient with TB. We could not find association (p >0.05) with hemoptysis, pulmonary physical examination, previous TB or incarceration, lower educational level, LT CD4 count, HIV-1 viral load, number of previous opportunistic infections or white cell count.
Use of darunavir and enfuvirtide in a pregnant woman
(2009) Sued, Omar; Lattner, Julia; Gun, Ana; Patterson, Patricia; Abusamra, Lorena; Cesar, Carina; Fink, Valeria; Krolewiecki, Alejandro J.; Cahn, Pedro
A 41-year-old pregnant woman with multiple virological failures started darunavir, enfuvirtide, zidovudine and lamivudine at week 28 of pregnancy. During week 38, the patient had a viral load <400 copies/mL and a CD4 count of 180 cells/mm(3) (13%). The child was found to be in good health, with negative HIV-polymerase chain reactions at birth, at two and at six months.

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