Silvina Fernández Giuliano

Hospital Muñiz

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María Belén Bouzas

Hospital Muñiz

Inés Zapiola

Hospital Muñiz

Silvia Kademián

Ministerio de Salud

Claudia Rodríguez

Universidad de Los Andes, Chile

Horacio Salomón

University of Buenos Aires

Diego Cecchini

Argerich Hospital

Ana M Cañizal

Hospital Muñiz

Analía Cudolá

Ministerio de Salud

Rosa Bologna

Garrahan Hospital

Rodolfo Campos

Consejo Nacional de Investigaciones Científicas y Técnicas

Cooperative Institutions

University of Buenos Aires

Consejo Nacional de Investigaciones Científicas y Técnicas

Hospital Muñiz

Centro Científico Tecnológico - San Juan

Instituto de Investigaciones Biomédicas en Retrovirus y Sida

Garrahan Hospital

Ministerio de Salud

Asociación por los Derechos Civiles

South Texas Veterans Health Care System

Centro Científico Tecnológico - Tucumán

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Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014–15

Journal of Antimicrobial Chemotherapy (2016)

Emiliano Bissio María Gabriela Barbás MB Bouzas Analía Cudolá Horacio Salomón

In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level.To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology.This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm.Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The mean ± SD age was 35 ± 11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N.This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.

Christian ministry

HIV drug resistance

Resistance mutation

Antiretroviral treatment

Antiretroviral drug

10.1093/jac/dkw445

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Citations (30)

Short Communication: Hepatitis B Virus Harboring Nucleotide Deletions in the Basal Core Promoter in HBe-Positive HIV-Coinfected Patients Under Lamivudine Therapy

AIDS Research and Human Retroviruses (2010)

Lucila Cassino Natalia Laufer Silvina Fernández Giuliano María Belén Bouzas Jorge Quarleri

The presence of HBV genomes with deletions at the basal core promoter (BCP) is associated with more aggressive liver disease. This 3-year longitudinal analysis of two HIV-HBV-coinfected patients allowed identification of three deletions with dissimilar abundance and permanence into the HBV quasispecies composition. These deletions may contribute to HBV pathogenesis in HIV-coinfected individuals.

Viral quasispecies

Orthohepadnavirus

Liver disease

Pathogenesis

10.1089/aid.2010.0096

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Citations (2)

Utilización del ensayo COBAS AMPLICOR MONITOR HIV-1 en el diagnóstico temprano de la infección por HIV en pediatría

Ana M Cañizal Fernanda Canales González Silvina Fernández Giuliano Inés Zapiola María Belén Bouzas

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Pre-treatment drug resistance and HIV-1 subtypes in infants from Argentina with and without exposure to antiretroviral drugs for prevention of mother-to-child transmission

Journal of Antimicrobial Chemotherapy (2018)

Paula Aulicino Inés Zapiola Silvia Kademián María M Valle Silvina Fernández Giuliano

To assess the prevalence and patterns of pre-treatment HIV drug resistance (PDR) and HIV-1 subtype in infants from Argentina with exposure to different antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT).HIV-1 genotyping was performed in 115 infants (median age = 2.3 months) born between 2007 and 2014 to screen for drug resistance mutations (DRMs) before starting first-line ART. HIV-1 subtype was characterized by phylogenetic and recombination analysis.Overall, DRMs were found in 34 of 115 infants (PDR level 30% to any ARV, 3.5% to PIs, 12% to NRTIs and 22% to NNRTIs). Of the 115 infants, 22 (19.1%) were ARV-unexposed. Another 93 were ARV-exposed: 28 (24.3%) to short-course zidovudine monotherapy ARV prophylaxis; 25 (21.7%) to nevirapine-based ARV prophylaxis; 12 (10.4%) to perinatal infant zidovudine prophylaxis + maternal combination ART with NNRTIs; and 28 (24.3%) to perinatal infant zidovudine prophylaxis+maternal combination ART with PIs. Transmitted drug resistance among ARV-unexposed infants was 32% (5% to PIs, 9% to NRTIs and 18% to NNRTIs). ART-exposed infants showed multi-class ARV resistance. Importantly, vertical transmission of a triple-class-resistant virus was confirmed in one case. Patterns of DRMs predicted high-level resistance to NNRTIs in a similar and high proportion (>50%) of infants with at least one DRM independently of ARV exposure. BF recombinants were found in 74%, subtype B in 20%, subtype C in 3% and novel AG and AB recombinants in 3%.PDR in HIV-1-infected children from Argentina is among the highest reported, jeopardizing successful lifelong suppressive ART as well as the efficacy of current PMTCT regimens.

Nevirapine

10.1093/jac/dky486

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Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina

Revista Española de Quimioterapia (2021)

Diego Cecchini Javier Sfalcin Inés Zapiola Alan Gómez Silvina Fernández Giuliano

Objective. Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). Patients and Methods. Retrospective study in a cohort of 40 naïve HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. Results. TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were <2.3% of viral population and ML was <350 c/mL for 77.8% of them. Conclusion. NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

Viral quasispecies

HIV drug resistance

10.37201/req/022.2021

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Citations (3)

Classical swine fever among wild boar in Tuscany.

E. Tasselli Silvina Fernández Giuliano

Wild boar

Classical swine fever

BOAR

African Swine Fever

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Characterization of the basal core promoter and precore regions in anti-HBe-positive inactive carriers of hepatitis B virus

International Journal of Infectious Diseases (2011)

María Mora González López Ledesma Omar Galdame Belén Bouzas Luciana Tadey Beatriz Livellara

BackgroundThe study of hepatitis B virus (HBV) genomic heterogeneity has become a major issue in investigations aimed at understanding the relationship between HBV mutants and the wide spectrum of clinical and pathological conditions associated with HBV infection. Although most chronically infected HBV patients are inactive carriers, several virological aspects of this state remain unclear.MethodsIn order to determine the prevalence and clinical significance of mutations in the basal core promoter (BCP) and precore (pC) regions among inactive carriers, the nucleotide sequences from 41 inactive carriers were analyzed and compared with those from 29 individuals with chronic active hepatitis.ResultsGenotypes A (24.3%), D (37.1%), F1b (12.9%), and F4 (18.6%) were the most prevalent. Mutations in the BCP/pC regions were observed in most of the inactive carriers (92.7%) and in most of the patients with chronic active hepatitis (93.1%). The prevalence of mutation 1764A was significantly higher in patients with chronic active hepatitis (65.5%) than in inactive carriers (36.6%) (p = 0.038), whereas the prevalences of mutations at the other positions analyzed were not significantly different. Older patients (>50 years) showed BCP/pC patterns with a higher number of substitutions. Mutations were found to be biased by genotype: the 1896A mutation was highly prevalent in genotypes D and F4, while alternative substitutions in the pC region were more prevalent in genotypes A and F1b.ConclusionsMutations in the BCP/pC regions are the hallmark of chronic anti-HBe-positive individuals; nevertheless, the even distribution of mutations in active and inactive carriers suggests that BCP/pC mutations may occur during HBV infection not strictly related to the HBV infection activity.

Basal (medicine)

10.1016/j.ijid.2010.12.009

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Citations (18)

Evaluación comparativa de COBAS TaqMan HIV-1 y COBAS AMPLICOR HIV-1 para la cuantificación de carga viral plasmática de HIV-1

Fernanda Canales González Ana M Cañizal Silvina Fernández Giuliano María Belén Bouzas

TaqMan

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Hepatitis B virus in Buenos Aires, Argentina: genotypes, virological characteristics and clinical outcomes

Clinical Microbiology and Infection (2010)

Silvana Claudia Pezzano Carolina Torres Hugo Fainboim María Belén Bouzas Teresa Schroder

HBeAg

Orthohepadnavirus

10.1111/j.1469-0691.2010.03283.x

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Citations (43)

[HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area].

PubMed (2016)

Inés Zapiola Diego Cecchini Silvina Fernández Giuliano Marina González Martínez Claudia Rodríguez

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Resistance mutation

HIV drug resistance

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Citations (4)