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Publications
Publications (330)
More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and...
Se desconoce si las personas que viven con el VIH (PVV) tienen un mayor riesgo de contraer la infección por SARS-CoV-2. Los estudios serológicos prospectivos pueden permitir análisis de seroincidencia. Este estudio prospectivo incluyó a PVV, sin antecedentes de vacunación contra SARS-CoV-2, de la Ciudad Autónoma de Buenos Aires (CABA) y Gran Buenos...
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...
Biobanks are instrumental for accelerating research. Early in SARS-CoV-2 pandemic, the Argentinean Biobank of Infectious Diseases (BBEI) initiated the COVID19 collection and started its characterization.
Blood samples from subjects with confirmed SARS-CoV-2 infection either admitted to health institutions or outpatients, were enrolled. Highly expos...
La pandemia de COVID-19 ha puesto en jaque a los sistemas de salud en el mundo; la vinculación entre la investigación biomédica y la práctica asistencial ha probado ser un requisito fundamental para dar respuesta a la misma de manera eficiente y rápida. En este sentido, los biobancos se constituyen como un componente clave ya que favorecen el almac...
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 (HI...
Objective:
Short-read next-generation sequencing (NGS) has been implemented to study the resistance profile of HIV as it provides a higher sensitivity than Sanger sequencing. However, short-reads only generates a consensus view of the viral population rather than a reconstruction of the viral haplotypes. In this study, we evaluated the resistance...
Background
HCV coinfection among people living with HIV might perturb immune function and HIV persistence. We aimed to evaluate the impact of HCV clearance with direct acting antivirals (DAA) on immune activation and HIV persistence in HIV/HCV-coinfected individuals on antiretroviral therapy (ART).
Methods
In a prospective observational study, ART...
During the acute phase of HIV-1 infection, a strong readaptation occurs in the viral population. Our objective was to analyze the post-transmission mutations associated with escape to the cytotoxic immune response and its relationship with the progression of the infection. In this study, a total of 17 patients were enrolled during acute/early prima...
The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/...
(A) Proportion of PD-1+ cells observed post-expansion on bulk CD8+ TEM and TTE cells from DT and ET individuals. (B) Proportion of HIV-specific cells (either Nef-specific or p24-specific) cells, identified on the bases of cytokine production and/or degranulation capacity, observed post-expansion on CD8+ TEM and TTE cells from DT and ET individuals....
Gating strategy used for the identification of the studied cellular populations, by flow cytometry. (A) To study CD8+ T-cell polyfunctionality, initial gating was performed on a forward scatter area (FSC-A) vs. FSC-height (FSC-H) plot to remove doublets. Dead cells were then excluded on the bases of Zombie NIR fluorescence. Then, gating was perform...
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...
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 prior to ther...
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 im...
Gating strategy used for flow cytometry analysis of monocyte-derived macrophages (MDMs) (A) and CD4+ T-cells (B). First, doublets were excluded in a forward scatter (FSC)-height (FSC-H) versus an FSH-area (FSH-A) plot. Then, living cells were gated an FSC-A versus a side scatter (SSC) plot. Subsequently, infected cells were identified in an FSC-H v...
Background:
Recent studies indicate that there is selection bias for transmission of viral polymorphisms associated with higher viral fitness. Furthermore, after transmission and before a specific immune response is mounted in the recipient, the virus undergoes a number of reversions which allow an increase in their replicative capacity. These asp...
Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4...
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...
Background:
Rilpivirine-based regimens are now preferred or alternative first-line regimens according to many HIV treatment guidelines. Recently, a surveillance study conducted in our country determined that prevalence of pretreatment resistance to first-generation NNRTIs was 10%. The aim of this study was to analyze the prevalence of resistance m...
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...
Importance:
Although the induction of ADCC-mediating antibodies in HIV-infected subjects has been extensively documented, the association of these antibodies with protection from disease progression is poorly understood. Here, we demonstrate that plasma IgA is a factor capable of modifying the magnitude of IgG-mediated ADCC in HIV infection, mitig...
The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percent...
Tuberculosis (TB) is the leading cause of death among HIV positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective anti-tubercular imm...
Background:
Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI...
The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8+ T-cell differentiation and viral control is needed. Here, an immunoph...
The HIV-1 epidemic in South America is dominated by pure subtypes (mostly B and C) and more than 7 BF and BC recombinant forms. In Argentina, circulating recombinant forms (CRFs) comprised of subtypes B and F make up more than 50% of HIV infections. For this study, 28 HIV-1 primary isolates were obtained from patients in Buenos Aires, Argentina and...
BACKGROUND: Th17 and Treg subsets have been related to HIV/SIV disease progression. Their role and direct relation with specific HIV-adaptive T cell responses during primary HIV infection (PHI) are unexplored topics. Aim: To analyze the frequency and balance of Th17 and Treg subsets and the correlation with clinical parameters, immune activation an...
ORAL PRESENTATION. Th17 and Treg subsets have been related to HIV/SIV disease progression. Their relation with specific HIV-adaptive T-cell responses during primary HIV-infection (PHI) is still unexplored. Aim: to analyze Th17 and Treg subsets, their balance and correlation with clinical parameters and specific anti-HIV responses during early infec...
Background: Th17 and Treg subsets have been related to HIV/SIV disease progression. Their role and direct relation with specific HIV-adaptive T-cell responses during primary HIV-infection (PHI) are largely unexplored topics. Aim: To analyze Th17 and Treg subsets, their balance and correlation with clinical parameters and specific anti-HIV responses...
Objective:
Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years.
De...
The important role of the CD8(+) T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity -VIA- and polyfunctionality) of the...
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). There...
In HIV infection, initiation of treatment is associated with improved clinical outcom and reduced rate of sexual transmission. However, difficulty in detecting infection in early stages impairs those benefits. We determined the minimum testing rate that maximizes benefits derived from early diagnosis.
We developed a mathematical model of HIV infect...
Baseline distributions of variables relevant for the analysis of modeĺs predictions about the natural history of HIV infection. The distribution of patient´s age at infection, CD4 count and viral load are shown.
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Patient´s age at progression to AIDS and death predicted in by the model in the absence of treatment.
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Survival curves obtained by Kaplan Meier analysis and their natural logarithmic transformation. Curves for the total population and separating HIV related death from other causes of death predicted by the model for HIV-positive individuals after diagnosis.
(TIF)
Curve fitted to the natural logarithmic transformation of the survival curve related to AIDS mortality. Three different functions were adjusted to each of the three age intervals shown in the figure. Functions details are provided in Text S1.
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Curves describing rates of disease progression and death according to variations in viral load, CD4 count and patient’s age. Four different scenarios are shown according to the patient’s age at the moment of infection. Although this is a continuous variable, in order to simplify the explanation only four different ages at infection are shown. For e...
Comparison of modeĺs output run under diagnosis route 1 (fixed diagnosis delay) and diagnosis route 3 (fixed testing rate). For each annual testing rate, results from using the rate or using the diagnosis delay fixed at the third quartile (Q75) of the distribution of diagnosis delays are shown. Comparisons performed for mortality during the first y...
Viral Load-dependent CD4 count decay. The linear function adjusted to model the reduction in CD4 count determined by viral load is shown.
(TIF)
Median CD4 count at initiation of HAART according to time from infection to diagnosis. Simulations were run under the following combinations of CD4 count threshold to initiate HAART and annual rate of detection through symptomatology (DTS) for the following conditions: Initiation of HAART at 200 (grey line), 350 (light blue line) and 500 (dark blue...
Times to AIDS and times to death according to patient´s age at infection death predicted by the model in the absence of treatment.
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Baseline distributions for Mortality rates analysis. Distribution of patientś age at infection, patientś age at initiation of HAART, viral load and CD4 count at the moment of infection are shown.
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Patientś age at death. Distribution of patientś age at death during the simulations runs to determine the general mortality rates of HIV-positive individuals after diagnosis.
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Proportion of HIV positive individuals unaware of their infection observed at any time in a steady state situation for each of the analytical settings. Simulations output from the same model runs analyzed for Figure 3, were also analyzed to determine the proportion of HIV-positive individuals unaware of their serological status as those who did not...
Distribution of the total times to AIDS and times to death predicted by the model in the absence of treatment.
(TIF)
Recently, it was shown that peripheral blood FOXP3+CD4+ T cells are composed of three phenotypic and functionally distinct subpopulations. Two of them having in vitro suppressive effects were characterized as resting Treg cells (rTregs) and activated Treg cells (aTregs). A third subset, identified as FOXP3+ non-Tregs, does not display any suppresso...
We previously reported a naturally occurring BF intersubtype recombinant Vpu variant with augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain (TMD) and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas CTD α-helix II corresponded to subtype F1. This w...
It is believed that initial encounter between HIV and the human host triggers a complex series of events that dictate future disease course. Inter-individual differences among the host-players involved in these processes seem to early determine different rates of disease progression. Here we were aimed at studying the relationship between innate an...
Background The Department of Oran is located on the North of Argentina and is populated by native settlements and urbanized areas. During the last twelve years, an increasing number of HIV infections have been detected. We previously reported a highly limited HLA diversity with a reduced number of HLA-A and B alleles present at high prevalence. The...
Tuberculosis (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 s...
Maternal human immunodeficiency virus (HIV) coinfection has been associated with increased hepatitis C virus (HCV) mother-to-child transmission (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV disease would not have increased HCV MTCT.
The NISDI Perinatal and LILAC cohorts enrolled HIV-infected pregnant women and their...
In Argentina, HIV diagnosis in adults is made using one or two enzyme immunoassay tests and a confirmatory test. These strategies may fail to identify infected individuals during early primary infection, which represents an important public health problem among groups with a high HIV incidence, such as men who have sex with men (MSM) (6.3% persons/...
Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the...
There are two new drugs approved and several in development for treatment of chronic HCV; among them nitazoxanide (NTZ). Twelve HIV/HCV genotype 1 co-infected patients were enrolled prospectively to receive a 30 days course of oral NTZ 500 mg bid. This therapy was well tolerated in this group of HIV patients co-infected with HCV genotype 1. Neverth...
We studied drug resistance mutations (DRMs) in 2623 pol sequences. Out of 94,828 amino acid substitutions that were detected, 8749 corresponded to nucleoside reverse transcriptase inhibitor (NRTI), 3765 to nonnucleoside reverse transcriptase inhibitor (NNRTI), and 7141 to protease inhibitor (PI) resistance-associated mutations. The most common DRMs...
HIV Nef-mediated up-regulation of invariant chain (Ii chain, also CD74) is presumed to play an active role in HIV immunopathogenesis. However, this has not been definitely ascertained. In order to help elucidate this hypothesis, Ii chain, CD4, HLA-DR and HLA-ABC expression was analyzed ex vivo in monocyte-derived macrophages (MDMs) from HIV(+) subj...
Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial.
Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 199...
A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patie