Research Interests: Molecular Evolution, Biology, Virology, Medicine, HIV, and 15 moreMolecular Epidemiology, Phylogeny, Humans, Cluster Analysis, AIDS, Molecular Phylogenetics and Evolution, South America, Clinical Sciences, Recombinant DNA, Ciencias Biológicas, Genotype, Time Factors, Genetic Recombination, Recombination, and HIV infections
Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The... more
Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The polymerase regions of several of these resistant viruses were sequenced and were found to share either of two codon alterations at site 184 in reverse transcriptase (ATG to ATA [methionine to isoleucine] and ATG to GTA [methionine to valine]). The biological relevance of these substitutions for 3TC was confirmed by site-directed mutagenesis with the SIVmac239 infectious recombinant clone of SIV.
Research Interests: Microbiology, Medical Microbiology, Biology, Virology, Medicine, and 15 moreCell line, Humans, Mutation, Virus, Microbial genetic and drug resistance, T lymphocytes, Molecular cloning, Codon, Simian Immunodeficiency Virus, Reverse Transcriptase, Lamivudine, Site-directed Mutagenesis, Pharmacology and pharmaceutical sciences, reverse transcriptase inhibitors, and stereoisomerism
Background Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population. Development of an adequate immune response will determine disease progression or... more
Background Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world’s population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20–30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection. Methods A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo...
Research Interests: Microbiology, Internal Medicine (General Medicine), Immunology, Cytokines, Tuberculosis and Infectious Disease, and 15 moreInfectious Diseases, Medicine, Human, Biological Sciences, Tuberculosis, Mycobacterium tuberculosis, Biomedical science, Coinfection, Inmunology, CIENCIAS DE LA SALUD, Immune system, Neumología, Enfermedades Infecciosas, Pulmonary Tuberculosis, and Medical and Health Sciences
We have shown that umbilical cord blood mononuclear cells (CBMC) are at least as sensitive as peripheral blood mononuclear cells (PBMC) for isolation of human immunodeficiency virus type 1 from the PBMC of infected individuals. Viral... more
We have shown that umbilical cord blood mononuclear cells (CBMC) are at least as sensitive as peripheral blood mononuclear cells (PBMC) for isolation of human immunodeficiency virus type 1 from the PBMC of infected individuals. Viral replication was more efficiently monitored by a p24 antigen capture assay than by a viral reverse transcriptase test, regardless of whether CBMC or PBMC were employed. We also found that CBMC and PBMC yielded similar results with regard to the susceptibility profiles of both wild-type and drug-resistant variants of human immunodeficiency virus type 1 for 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine. Finally, viruses isolated on CBMC could be routinely grown on PBMC and vice versa.
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Background: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential... more
Background: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8+ T-cell function and phenotype before therapy and HIV persistence on ART. Methods: Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics. Results: Elevated immune activation, dominance of monofunctional CD8+ T cells, and skewed distribution of memory profile were observed before ART. After ART ini...
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In vitro selection in MT-4 cells was used to generate human immunodeficiency virus-type 1 (HIV 1) variants that are resistant to 2',3'-dideoxycytidine (ddC), 2',3'-didcoxyinosine (ddI) and the (-) enantiomer of 2'... more
In vitro selection in MT-4 cells was used to generate human immunodeficiency virus-type 1 (HIV 1) variants that are resistant to 2',3'-dideoxycytidine (ddC), 2',3'-didcoxyinosine (ddI) and the (-) enantiomer of 2' ,3'-dideoxy-3'-thiacytidine (3TC). The complete reverse transcriptase open reading frames of these viruses, and portions of flanking protease and integrase within the pol gene, were cloned and sequenced by polymerase chain reaction (PCR) techniques. Mulalions were observed at each of amino acid sites 65 (Lys → Arg: AAA → AGA) and 184 (Met → Val: ATG → GTG) when ddC was used in this protocol, and at site 184 only when either 3TC or ddl was employed. These mutations were introduced into the pol gene of infectious recombinant HXB2-D DNA by site-directed mutagenesis to confirm, by viral replication assay, their importance in conferring resistance against these drugs. A recombinant virus containing the site 65 mutation only possessed greater than 10-...
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Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional"... more
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg. Also, IL-10, TGF-β, IFN-γ production, and the suppressor capacity of uTregs were analyzed in cocultures with effector lymphocytes and compared with the effect of regulatory T cells (Tregs). We found diminished expression of CD39 and higher levels of PD1 on uTreg compared to cTreg in both HIV-TB and healthy donors (HD). In addition, uTreg and ...
Research Interests: Immunology, Biology, Cytokines, Medicine, Human, and 3 morePopulation, Immune system, and Inmunología
To evaluate the impact of Chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8T-cell (CTL) response in an HIV Elite Controller (EC). Three blood samples were obtained from an EC at 27 days (EC-CHIKV,Sample 1, S1); 41... more
To evaluate the impact of Chikungunya virus (CHIKV) infection on the quality of the HIV-specific CD8T-cell (CTL) response in an HIV Elite Controller (EC). Three blood samples were obtained from an EC at 27 days (EC-CHIKV,Sample 1, S1); 41 days (S2) and one year (S3) after CHIKV infection. Additionally, samples from other nine ECs and nine viremic Chronics were obtained. CD4 T-cell counts, viral load (VL) and immune activation were recorded. NK cells and HIV-specific CTL quality were evaluated. Data was analysed using non-parametric statistics. A male HIV EC was confirmed for CHIKV infection. At S1, he presented 211 CD4 T-cells/μl, a HIV VL blip (145 copies/ml) and high T-cell activation. NK cell percentage and activation were higher at S2. All parameters were recovered by S3. CTLs at S1 were exclusively monofunctional with a high proportion (>80%) of degranulating CTLs. By S3, CTL polyfunctionality was more similar to that of typical EC. The distribution of CD8T-cell memory subse...
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In Argentina, HIV diagnosis is reached by voluntary testing or symptom-based case findings. However, because of the high proportion of infected individuals unaware of their serologic status new strategies are required. In this article we... more
In Argentina, HIV diagnosis is reached by voluntary testing or symptom-based case findings. However, because of the high proportion of infected individuals unaware of their serologic status new strategies are required. In this article we show how a mathematic model predicts the impact of expanding HIV testing in Argentina. The model is based on time-dependent Markov matrixes and applies parameters-dependent transition-probabilities obtained from both national and international cohort studies. Outputs include time on clinical stages and therapy regime, CD4-count, viral-load, infection-state and age; mortality rates and proportion of unidentified infection at a population-level. Simulations were performed for current testing strategy and for a theoretical scenario with earlier diagnosis. We show how our prediction suggests that diagnosis before onset of symptoms would increase life expectancy by 10.7 years. Also, we show how a reduction of time to diagnosis to 5 or less years from inf...
Research Interests: Demography, Argentina, Medicine, HIV, Antiretroviral Therapy, and 15 moreHumans, Markov chains, Medicina, Life Expectancy, CIENCIAS DE LA SALUD, SIDA, Time Factors, Survival Rate, Highly Active Antiretroviral Therapy, Modelo Matemático, Enfermedades Infecciosas, Early Diagnosis, Delayed Diagnosis, Viral Load, and HIV infections
Co-infections with HIV and HCV/HBV are frequently found due to the similar routes of transmission (sexual, parenteral and vertical). Since the introduction of highly active antiretroviral therapy (HAART) there has been a notably decrease... more
Co-infections with HIV and HCV/HBV are frequently found due to the similar routes of transmission (sexual, parenteral and vertical). Since the introduction of highly active antiretroviral therapy (HAART) there has been a notably decrease in patients morbidity and mortality, nevertheless with the prolonged survival, many of these patients are at risk of developing chronic complication, secondary to the infection of hepatotropic viruses. End stage liver disease is one of the main causes of morbid-mortality among HIV patients in developed countries. Nowadays there are new available therapies, diagnostic and follow up techniques for HBV and HCV, what provides a better control of both co-infections.
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Research Interests: Bioinformatics, Immunology, Life Sciences, Argentina, Medicine, and 15 moreMultidisciplinary, Western blotting, Humans, Biomedical Research, Haplotypes, Polymerase Chain Reaction, PLoS one, Ciencias Biológicas, Hiv seropositivity, Disease Progression, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, Asymptomatic, Viral Load, Genetic factors, and Human leukocyte antigen
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Research Interests: Immunology, Immune response, Biology, Medicine, HIV, and 15 moreCortisol, Humans, Female, Male, Coinfection, Middle Aged, Adult, Dehydroepiandrosterone, Blood Plasma, Interferon gamma, Adrenal glands, hydrocortisone, antiretroviral treatment, immune reconstitution inflammatory syndrome, and HIV infections
Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus... more
Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus type 1 (HIV-1) infection. DC-SIGN binds HIV-1 gp120 and efficiently transmits the virus to T CD4 + cells, which become the center of viral replication. Semen represents the main vector for HIV-1 dissemination worldwide. In the present study we show that human seminal plasma (SP), even when used at very high dilutions (1:10 4 to 1:10 5 ), markedly inhibits the capture and transmission of HIV-1 to T CD4 + cells mediated by both DCs and B-THP-1-DC-SIGN cells. In contrast, SP does not inhibit the capture of HIV-1 by DC-SIGN-negative target cells, such as the T-cell line SupT-1, monocytes, and activated peripheral blood mononuclear cells. The SP inhibitor has a high molecular mass (>100 kDa) and directly interacts with DC-SIGN-positive target cells bu...
Research Interests: Biology, Virology, Medicine, Dendritic Cells, HIV, and 15 moreBiological Sciences, Cell line, Humans, Male, Dendritic cell, Middle Aged, Human immunodeficiency virus, Adult, Molecular Mass, Semen, Sexually Transmitted Disease, Seminal Plasma, Cell Adhesion Molecules, Medical and Health Sciences, and HIV infections
BackgroundTuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to... more
BackgroundTuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to Mycobacterium tuberculosis (Mtb), we assessed basal and Mtb‐induced proliferation, cytokine production, and expression of signalling lymphocytic activation molecule (SLAM), inducible costimulator (ICOS) and programmed death‐1 (PD‐1) on T lymphocytes from HIV‐positive individuals coinfected with TB, HIV‐positive subjects, TB patients and healthy donors (HD).FindingsHIV‐TB patients showed increased ICOS, SLAM and PD‐1 basal levels on T lymphocytes, whereas HIV‐positive individuals displayed elevated levels of SLAM and PD‐1, TB patients high levels of SLAM, and HD low levels of the three proteins. Mtb‐stimulation enhanced ICOS expression in the four groups, but only TB and HD increased SLAM and PD‐1 levels.ConclusionsThese data show the immune deregulat...
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Research Interests: Microbiology, Immunology, Infectious Diseases, Medicine, Biological Sciences, and 15 moreHumans, Female, Male, Infectious, Human immunodeficiency virus, Adult, Oxford university, Combination drug therapy, Lamivudine, Interleukin, Nevirapine, Phase II Trial, Medical and Health Sciences, indinavir, and HIV infections
Cell-mediated immunity, cytokines induced during the specific immune response and T-cell populations are crucial factors for containing Mycobacterium tuberculosis infection. Recent reports suggest a cross-regulation between adrenal... more
Cell-mediated immunity, cytokines induced during the specific immune response and T-cell populations are crucial factors for containing Mycobacterium tuberculosis infection. Recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids and dehydroepiandrosterone, DHEA) and the function of antigen-presenting cells (APCs). Therefore, we investigated the role of adrenal hormones on the functional capacity of M. tuberculosis-induced dendritic cells (DCs). Cortisol significantly inhibited the functions of M. tuberculosis-induced DCs. Interestingly, the presence of DHEA enhanced the M. tuberculosis-induced expression of MHC I, MHC II and CD86 and also increased ERK1/2 phosphorylation. Moreover, DHEA improved the production of IL-12 in response to M. tuberculosis stimulation, diminished IL-10 secretion and could not modify TNF-α synthesis. Importantly, we observed that DHEA enhanced the antigen-specific T-cell proliferation and IFN-γ production induced by M. tuberculo...
Research Interests: Immunology, Biology, Cytokines, STEROIDS, Medicine, and 14 moreDendritic Cells, Tuberculosis, Humans, Mycobacterium tuberculosis, Dendritic cell, Phenotype, CD, CIENCIAS DE LA SALUD, Ciencias Biológicas, Immune system, Dehydroepiandrosterone, Enfermedades Infecciosas, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, and hydrocortisone
Research Interests: Biology, Virology, Drug interactions, Medicine, HIV, and 15 moreBiological Sciences, Cell line, Humans, Virus, Drug Resistance, Phenotype, Molecular cloning, Human immunodeficiency virus, Open Reading Frame, Antiviral Agents, Interferon Alpha, Neutralization tests, Zalcitabine, Stavudine, and Medical and Health Sciences
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Cloned variants of human immunodeficiency virus type 1 that contain the K65R mutation in reverse transcriptase have previously been shown to display approximately 10- to 30-fold resistance against 2',3'-dideoxycytidine,... more
Cloned variants of human immunodeficiency virus type 1 that contain the K65R mutation in reverse transcriptase have previously been shown to display approximately 10- to 30-fold resistance against 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 2',3'-dideoxy-3'-thiacytidine. On the basis of tissue culture studies with both primary T cells and established cell lines, we now report that the K65R mutation confers approximately 12- to 15-fold resistance to 9-(2-phosphonylmethoxyethyl)adenine (PMEA). Likewise, a chain termination system revealed that mutated recombinant K65R reverse transcriptase displays resistance to PMEA diphosphate, the active metabolite of PMEA, in cell-free enzyme assays. Parallel studies have shown that the M184V mutation in reverse transcriptase, associated with high-level resistance against the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine, does not confer resistance to PMEA in tissue culture. Viruses and enzymes that i...
Research Interests: Microbiology, Medical Microbiology, Biology, Virology, Medicine, and 14 moreHIV, Humans, Mutation, Virus, Plant tissue Culture Techniques, Microbial genetic and drug resistance, Molecular cloning, Antimicrobial agents, Cell free System, Reverse Transcriptase, Adenine, Antiviral Agents, Pharmacology and pharmaceutical sciences, and HIV infections
The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete... more
The technique of in vitro selection was used to generate variants of the human immunodeficiency virus type 1 that are resistant to 2',3'-dideoxycytidine (ddC). Most of the pol regions of such viruses, including the complete reverse transcriptase open reading frame and portions of flanking protease and integrase genes, were cloned and sequenced, using PCR-based procedures. Mutations were variously detected at amino acid site 65 (Lys-->Arg; AAA-->AGA) and at a previously reported codon, site 184 (Met-->Val; ATG-->GTG). We introduced the site 65 mutation into the pol gene of infectious, cloned HxB2-D DNA by site-directed mutagenesis in order to confirm by viral replication assay the importance of this site in conferring resistance to ddC. The recombinant virus possessed greater than 10-fold resistance against this compound in comparison with parental HxB2-D. Cross-resistance of approximately 20- and 3-fold, respectively, was detectable against the (-) enantiomer of ...
Research Interests: Microbiology, Molecular Biology, Medical Microbiology, Biology, Virology, and 15 moreMedicine, HIV, Humans, Mutagenesis, Mutation, Virus, Molecular cloning, Codon, Amino Acid Sequence, Base Sequence, Reverse Transcriptase, Lamivudine, Molecular Sequence Data, Zalcitabine, and Pharmacology and pharmaceutical sciences
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Background: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure. Several strategies have been proposed to achieve a functional... more
Background: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure. Several strategies have been proposed to achieve a functional cure, some of them based on immune-mediated clearing of persistently infected cells. Here, we aimed at identifying factors related to CD8TC and CD4TC quality before cART initiation that associate with the persistence of CD8TC antiviral response after cART, inflammation levels, and the size of the viral reservoir. Methods: Samples from 25 persons living with HIV were obtained before and after (15 months) cART initiation. Phenotype and functionality of bulk and HIV-specific T cells were assayed by flow cytometry ex vivo or after expansion in pre-cART or post-cART samples, respectively. Cell-Associated (CA) HIV DNA (total and integrated) and RNA (unspliced [US] and multiple spliced [MS]) were quantitated by real-time PCR on post-cART samples. Post-cART pl...
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Research Interests: Heterosexuality, Argentina, Adolescent, Medicine, Hepatitis C, and 15 moreHIV, Hepatitis B, Humans, Female, Male, Injecting Drug Use, Hepatitis C Virus, Hiv Infection, Human immunodeficiency virus, Adult, Hepatitis B virus, Cross Sectional Studies, Hepacivirus, Medical and Health Sciences, and HIV infections
Research Interests: Demography, Epidemiology, Argentina, Medicine, HIV, and 15 moreHumans, Male, Logistic Regression Analysis, Aged, Middle Aged, Human immunodeficiency virus, Adult, Cross Section, Analysis of Variance, Condoms, Cross Sectional Studies, Non Governmental Organization, Logistic Models, High risk, and HIV infections
The drug resistance profile of treatment-naive HIV-infected individuals living in Buenos Aires, Argentina, was studied. Samples taken from 94 drug-naive individuals with established HIV infection and 13 patients with primary HIV infection... more
The drug resistance profile of treatment-naive HIV-infected individuals living in Buenos Aires, Argentina, was studied. Samples taken from 94 drug-naive individuals with established HIV infection and 13 patients with primary HIV infection were assessed by nucleotide sequencing and LiPA. The prevalence of drug-associated primary mutations in individuals with established infection was very low. In the viral protease region, 1/86 (1.2%) individuals carried the D30N mutation, whereas 1/85 (1.2%) had the M41L mutation in the reverse transcriptase (RT) region. Secondary mutations in both the protease and RT regions were found in almost 90% of the individuals. In individuals with primary infection, primary mutations were detected in 2/13 (15.4%) patients, one of them carrying M46I mutation in the protease while the other patient had a mutation at codon 184 of the RT. In accordance with current drug resistance testing guidelines, the results of this study suggest that susceptibility tests n...
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Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury hepatic decompensation, and decreased survival than that observed in an HIV-monoinfected population. While... more
Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury hepatic decompensation, and decreased survival than that observed in an HIV-monoinfected population. While prevalence studies on HIV/HCV coinfection have been performed in the U.S. and in some European countries, little is known about HCV genotype distribution in Latin America. The main objective was to evaluate the HCV prevalence and genotypes among HIV co-infected patients, and their relationship with HCV viral load, serum ALT level and T lymphocyte CD4+ cell count. These data pursue to increase the knowledge from South America about a pressing problem from HIV-infected patients. Retrospectively collected specimens from 593 HIV-positive individuals in Argentina were tested for anti-HCV These were analyzed for HCV-RNA qualitatively and quantitatively. The HCV genotype was determined by the RFLP method. One hundred and twenty-nine (21.7%) HIV-infected indiv...
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Introduction The aim of our study was to analyse the frequency of primary mutations associated with HIV drug resistance in a population of children born to HIV-infected mothers. Design A prospective study included newly HIV-diagnosed... more
Introduction The aim of our study was to analyse the frequency of primary mutations associated with HIV drug resistance in a population of children born to HIV-infected mothers. Design A prospective study included newly HIV-diagnosed children treated at two public paediatric hospitals. Patients and methods Clinical and antiretroviral therapy (ART) data were collected in mother-child pairs. HIV-1 subtyping and ART resistance mutations were assayed in children by sequencing a region of HIV pol gene. Results: A total of 67 children were enrolled 22 less than 12 months of age, 20 between 1 and 5 years and 25 between 6 and 14 years. Six (9.0%) children had viral strains with at least one primary mutation associated with resistance to reverse transcriptase and protease inhibitors. A significantly ( P=0.019) higher frequency of resistance (22.7%, n=5/22) was found among children aged <12 months. Fourteen children (20.9%) had a subtype B HIV-1 strain and 53 (79.1%) had an inter-subtype B...
Research Interests: Microbiology, Medical Microbiology, Adolescent, Medicine, HIV, and 15 moreProspective studies, Humans, Child, Mutation, Female, Drug Resistance, Male, Infant, Clinical Sciences, Highly Active Antiretroviral Therapy, Nino, Molecular Sequence Data, Child preschool, Antiviral Therapy, and HIV infections
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Since anti-HIV treatment cannot cure the infection, many strategies have been proposed to eradicate the viral reservoir, which still remains as a major challenge. The success of some of these strategies will rely on the ability of... more
Since anti-HIV treatment cannot cure the infection, many strategies have been proposed to eradicate the viral reservoir, which still remains as a major challenge. The success of some of these strategies will rely on the ability of HIV-specific CD8 T-cells (CD8TC) to clear reactivated infected cells. Here, we aimed to investigate the phenotype and function of expanded CD8TC obtained from HIV subjects on combination antiretroviral therapy (cART), either initiated earlier (median = 3 months postinfection, ET: Early treatment) or later (median = 20 months postinfection, DT: Delayed treatment) after infection. Peripheral blood mononuclear cells from 12 DT and 13 ET subjects were obtained and stimulated with Nef and Gag peptide pools plus IL-2 for 14 days. ELISPOT was performed pre- and post-expansion. CD8TC memory/effector phenotype, PD-1 expression, polyfunctionality (CD107a/b, IFN-γ, IL-2, CCL4 (MIP-1β), and/or TNF-α production) and antiviral activity were evaluated post-expansion. Mag...
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{"__content__"=>"Interaction Between Macrophage Migration Inhibitory Factor and CD74 in Human Immunodeficiency Virus Type I Infected Primary Monocyte-Derived Macrophages Triggers the Production of Proinflammatory Mediators and Enhances Infection of Unactivated CD4 T Cells.", "sup"=>{"__content__"...more
Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74... more
Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74 membrane expression is upregulated in HIV-1-infected cells and the magnitude of its modulation correlates with immune hyperactivation in HIV-infected individuals. In addition, plasma level of the CD74 activating ligand macrophage migration inhibitory factor (MIF) is increased in infected subjects. However, the role played by MIF/CD74 interaction in HIV pathogenesis remains unexplored. Here, we studied the effect of MIF/CD74 interaction on primary HIV-infected monocyte-derived macrophages (MDMs) and its implications for HIV immunopathogenesis. Confocal immunofluorescence analysis of CD74 and CD44 (the MIF signal transduction co-receptor) expression indicated that both molecules colocalized at the plasma membrane specifically in wild-type HIV-infected ...
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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)... more
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 magnitu...
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Background Rilpivirine-based regimens are now preferred or alternative first-line regimens according to many HIV treatment guidelines. Recently, a surveillance study conducted in Argentina determined that prevalence of pre-treatment... more
Background Rilpivirine-based regimens are now preferred or alternative first-line regimens according to many HIV treatment guidelines. Recently, a surveillance study conducted in Argentina determined that prevalence of pre-treatment resistance to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 10%. The aim of this study was to analyse the prevalence of resistance mutations to newer generation NNRTIs in the population starting ART in Argentina. Methods We analysed the prevalence of resistance mutations to rilpivirine and etravirine (according to the IAS list), obtained through a nationally representative pre-treatment HIV-drug resistance (PDR) surveillance study performed in Argentina in 2014-2015. Briefly, 25 ART-dispensing sites throughout the country were randomly chosen to enrol 330 adults starting ART. Samples were processed with Trugene (Siemens)® and analysed using the Stanford algorithm. Results All 270 samples corresponding to participants with ...
Research Interests: Microbiology, Medical Microbiology, Argentina, Medicine, HIV, and 15 moreHumans, Resistance, Female, Male, Clinical Sciences, Ciencias Biológicas, Prevalence, Middle Aged, Adult, Public Health Surveillance, Highly Active Antiretroviral Therapy, Viral Load, Rilpivirine, Antiviral Therapy, and HIV infections
Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understanding its role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC... more
Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understanding its role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC in HIV infection, abrogating its protective role. Plasma samples from 20 HIV-positive (HIV + ) subjects enrolled during primary HIV infection (PHI), 10 chronically infected subjects (chronic), and 7 elite controllers (EC) were used. ADCC was determined by using a fluorometric ADCC assay, before and after removal of plasma IgA. Data were analyzed by using nonparametric statistics. ADCC was documented in 80% of PHI enrollment samples and in 100% of PHI 12-month, chronic, and EC samples; it peaked after acute infection, reached a plateau in chronic infection, and decreased after initiation of antiretroviral treatment (ART). Significant associations between ADCC and disease progression were found only after removal of plasma IgA from 12-month PHI sample...
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Soon after HIV (Human Immunodeficiency Virus) was discovered, its characteristics level of diversity and variability was established. So far, within HIV-1 it is known that there exist 3 main groups, 9 subtypes and at least 12 recombinant... more
Soon after HIV (Human Immunodeficiency Virus) was discovered, its characteristics level of diversity and variability was established. So far, within HIV-1 it is known that there exist 3 main groups, 9 subtypes and at least 12 recombinant forms. Not only does this diversity affect taxonomy, but also prophylaxis and therapy for HIV infection. Numerous studies worldwide have demonstrated the influence this variability has on both diagnosis and monitoring assays as well as on the pathogenesis of HIV infection. In Argentina, from the molecular point of view, the epidemic shows a complex pattern. HIV-1 subtypes B and F have been described as well as a recombinant B/F form. Epidemiology and molecular data suggest high percentage levels and a great diversity of these recombinant forms in the heterosexual population.
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HIV-1 is characterized by its rapid genetic evolution and high diversity as a consequence of its error-prone reverse transcriptase and genetic recombination. This latter mechanism is responsible for the creation of circulating recombinant... more
HIV-1 is characterized by its rapid genetic evolution and high diversity as a consequence of its error-prone reverse transcriptase and genetic recombination. This latter mechanism is responsible for the creation of circulating recombinant forms (CRFs) found in nature. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by one highly prevalent circulating recombinant form, CRF12_BF, and many related BF recombinant forms. Since transcriptional transactivation of the HIV-1 long terminal repeat (LTR) promoter element requires the essential viral Tat protein, since these genetic structures underwent recombination in variants widely spread in South America, the aim of this work was to study transcriptional activity associated with the recombinant LTR and Tat elements. Differential transcriptional activity was measured for the BF recombinant LTR/Tat complex that is present in widely spread viral variants was demonstrated. This analysis demonstrate...
Research Interests: Genetics, Biology, Medicine, HIV, Protein Structure and Function, and 15 moreCell line, Humans, Child, Genetic Structure, South America, Clinical Sciences, Recombinant DNA, Molecular cloning, Adult, Genetic Recombination, Genetic variation, Retrovirology, Reverse Transcriptase, Acquired immunodeficiency syndrome, and reverse transcriptase polymerase chain reaction
Research Interests: Biology, Cytokines, Medicine, Multidisciplinary, HIV, and 15 moreCell Differentiation, Humans, Peptides, Phenotype, CD, PLoS one, Ciencias Biológicas, Highly Active Antiretroviral Therapy, Immunophenotyping, Disease Progression, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, Case Control Studies, Viral Load, HIV infections, and Programmed Cell Death 1 Receptor
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Background Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating... more
Background Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating recombinant form, CRF12_BF, and many related BF recombinant forms. In these genomic structures a recombination breakpoint frequently involved the vpu coding region. Due to the scarce knowledge of Vpu participation in the virion release process and its impact on pathogenesis and of the functional capacities of intersubtype recombinant Vpu proteins, the aim of this work was to perform a comparative analysis on virion release capacity and relative replication capacity among viral variants harboring either a BF recombinant Vpu or a subtype B Vpu. Results Our results showed that BF recombinant Vpu was associated to an increased viral particles production when compared to WT B variant in tetherin-expressing cell lines. This observation was tested in the context o...