DSpace Repository :: Browsing by Author "Figueroa, Maria Ines"

Browsing by Author "Figueroa, Maria Ines"

Now showing 1 - 13 of 13

A phase 4, single-arm, open-label, pilot study of maraviroc, raltegravir and darunavir/r in HIV-1 adults with triple class failure: TERCETO study
(2012) Patterson, Patricia; Magneres, Claudia; Sued, Omar; Fink, Valeria; Figueroa, Maria Ines; Cesar, Carina; Gun, Ana; Cahn, Pedro; Krolewiecki, Alejandro J.
The purpose of this phase 4, single-arm, open-label study was to evaluate the safety, tolerability, efficacy, antiviral and immunological activity of maraviroc (MVC) in combination with raltegravir (RGV) and darunavir/r (DRV/r) in adult HIV-1 infected patients (pts) with limited treatment options. HIV-1 pts with documented virologic triple class failure or multi-drug class resistance defined as the presence of Q151 complex, 69 insertion complex and/or≥3 TAMs for NRTIs and K103N, G190S+Y181C or Y188L mutants for NNRTIs and≥3 RAMs (L10F/I/R/V; M46I/L; I54V/M/L; V82A/F/T/S; I84V; L90M) for protease inhibitors (PIs) were offered a triple drug regimen consisting of MVC 150 mg BID, RGV 400 mg BID and DRV/r 600/100 mg BID. Safety, lipid profile and virologic efficacy were evaluated at week 4, 12, 24, 36 and 48. Between January 2010 and March 2012, 27 pts were enrolled. Screening failure rate was 52% due to undetectable viral load (pVL) or non R5 tropism type (Trofile™). Despite being heavily pre-treated pts, only 26% had negative tropism test at SCR. Baseline characteristics of 13 included pts were: 77% male, median age 43 years (IQR: 40.1–48.6), 38% had a prior AIDS-defining condition. Median BSL pVL was 23,350 cps/mL (4.4 log10) (IQR: 11,236–55,785) and median CD4 was 222 cells/mm3 (IQR: 179–318). Median time on NRTIs, NNRTIs and PIs were 10.7 (8.6–13.7), 1.7 (1.3–7.6) and 5.4 (4.7–10) years respectively. Pts had received a median of 2 PIs (IQR: 2–3). 8/13 pts showed thymidine analogue-associated mutations (TAMs), and≥2 were present in 5/13. Detectable NNRTI resistance-associated mutations (RAMs) were present in 10/13 patients. 9/13 had≥4 primary PI RAMs. At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis)=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1) and the remaining pts (11/13) achieved undetectable pVL and increased CD4 in 133 cell/mm3 from BSL (IQR: 81–174.5). Median total cholesterol levels increased from 162 mg/dL (IQR: 135-188) to 215 mg/dL (IQR: 182–237) between BSL/W48; median change in cholesterol levels: 40 mg/dL (IQR: 6.5-66). Salvage therapy including MVC, RGV and DRV/r achieved sustained reductions in pVL (<50 copies/mL) through 48 weeks of therapy in this pilot study with no treatment limiting toxicity.
Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters
(2011) Socias, Maria E.; Sued, Omar; Laufer, Natalia; Lázaro, Maria E.; Mingrone, Hugo; Remondegui, Claudio; Figueroa, Maria Ines; Cesar, Carina; Gun, Ana; Turk, Gabriela; Bouzas, Maria B.; Kavasery, Rosanna; Krolewiecki, Alejandro J.; Perez, Hector; Salomon, Horacio; Pryluka, Damian
Background Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial. Methods 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 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm3, B, C events or death) at 12 months among untreated patients. Results Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm3, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively. Conclusions In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.
Changes in lipid levels after 48 weeks of dual versus triple therapy observed in the GARDEL study
(2014) Cahn, Pedro; Andrade-Villanueva, Jaime; Arribas, Jose; Gatell, Jose; Lama, Javier; Norton, Michel; Patterson, Patricia; Sierra Madero, Juan; Sued, Omar; Figueroa, Maria Ines; Rolón, María José
Introduction Treatment with ritonavir-boosted protease inhibitors and nucleoside analogues frequently leads to rises in lipids, which might increase the cardiovascular risk. The aim of this study was to describe changes in lipid levels among HIV positive patients participating in the GARDEL study. Materials and Methods The GARDEL study compared the efficacy and safety of a dual therapy (DT) combination of LPV/r 400/100 mg BID+3TC 150 mg BID to a triple therapy (TT) with LPV/r 400/100 mg BID+3TC or FTC and a third investigator-selected NRTI in fixed-dose combination among HIV+ treatment naïve patients. We compared changes in lipid levels from baseline to week 48 in both arms. Results Patient's characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94 mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL TT). Changes in total cholesterol, LDL-C and HDL-C were higher in DT arm, compared to TT (32% DT vs 26% TT for cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT for HDL). Increase in triglycerides was higher in TT compared to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total cholesterol elevations were lower among patients receiving TDF compared to those treated with ZDV or ABC.
Clinical challenges in HIV/AIDS: Hints for advancing prevention and patient management strategies
(2016-8) Sued, Omar; Figueroa, Maria Ines; Cahn, Pedro
Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current estimate for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addition, circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda.
Clinical-epidemiological features of HIV-infected patients diagnosed at age of 50 years or older
(2012) Patterson, Patricia; Cahn, Susana; Sued, Omar; Fink, Valeria; Figueroa, Maria Ines; Cesar, Carina; Rojo, Marina; Ben, Graciela; Vazquez, Mariana; Cahn, Pedro
HIV/AIDS prevention and care efforts are directed to individuals of reproductive age (15–49 yrs). With the extension of sexual life of older people, they became a growing population at risk of HIV infection, usually not included in prevention strategies. In order to evaluate clinical profile of HIV/AIDS pts diagnosed at 50 yrs or older assisted in an HIV outpatient center in Buenos Aires, we retrospectively assessed clinical records of pts initiating care between Jan 1986 and Dec 2011. Age, CD4 cells and viral load (pVL) at HIV diagnosis and most recent value, opportunistic infections (OIs), co-morbidities and antiretroviral therapy (ARV) were recorded. Of 10,998 pts assisted in the 26-yr period, 495 (4.5%) were≥50 yrs old at HIV diagnosis; median annual diagnoses: 18.5 (IQR 3.3–30.3) without significant changes in the last 20 yrs. Demographics: median age 54.7 yrs (IQR 51.8–59.2, rank 50–80), 76.6% male. Risk behavior: HTX 61.4%, MSM 34.1%, others 4.4%. 55.4% of HIV diagnoses occurred during hospitalization or simultaneously with acute OIs. One third (n=176) had AIDS at diagnosis, 24% had history of STDs. HCV co-infection 5.7%, past HBV infection 28.1% and chronic HBV infection 5.1%. Median CD4 cells at HIV diagnosis: 223.5 (13.7%) (IQR 98.8–420.3), initial pVL 60,000 cp/mL (IQR 9,995.5–208,391). 69.3% of pts started ARV therapy during follow-up (FU), and the median time between diagnosis and treatment initiation was 3.4 mo (IQR 0.7–14); 56.9% of them started a non-nucleoside-based regimen (ZDV/3TC/EFV), 28.3% a PI-based regimen (ZDV/3TC/IDV) and 14.6% a nucleoside-based regimen (ZDV/ddI pre-HAART era). After a year (±6 mo), 63.8% pts achieved undetectable pVL and gained 136 CD4 cells from BSL (IQR 83–204). After 40.6 mo of FU (IQR 6.7-89.8), 66.3% are alive, 7.1% died (68.6% of HIV-related diseases) and 26.7% are lost to FU. Co-morbidities were present in 125 (25.3%), mainly hypertension, increased lipids, CVD and DBT. Among treated pts, 70.6% achieved pVL<50 cp/mL, with a median increase of CD4 cells up to 410 (22%) (IQR 281.5–563.9) from BSL. 51% (176) changed ARV therapy due to toxicity/AE: 54.5%, ARV failure: 29.5% and simplification: 14.8%. Stable HIV epidemic in older people reinforce the need of specific prevention approaches, while growing age of HIV individuals in care highlights to consider risks associated to older age. Late presentation to care needs to be specifically addressed. Response to treatment is remarkable high in this population.
Exposición ocupacional al virus de la hepatitis C
(2007) Ricart, Javier J.; Fink, Valeria; Cabrini, Mercedes; Figueroa, Maria Ines; Laufer, Natalia; Cahn, Pedro
La transmisión ocupacional de virus de hepatitis C (VHC) es un área de creciente preocupación dada la falta de profilaxis y la poca información de su prevalencia en el medio hospitalario. Sobre 128 exposiciones ocupacionales ocurridas en el Hospital Diego Paroissien entre1999 y 2003 hubieron 8 casos de exposición a VHC (6.3%) y un caso de seroconversión posterior a la exposición (0.8%). No existiendo en la actualidad terapia preventiva para VHC resulta de gran interés la posibilidad de tratamiento de la infección aguda. La mayor parte de los autores coincide en recomendar el tratamiento del episodio agudo de hepatitis por VHC basado en la evidencia actual, aunque aún no está bien definida la mejor estrategia diagnóstica y terapéutica. El acatamiento de las Normas de Precauciones Universales sigue siendo en la actualidad la más importante medida preventiva para evitar la infección ocupacional por VHC en el personal de salud y la de mejor equilibrio costo-beneficio.
Host Genetic Factors Associated with Symptomatic Primary HIV Infection and Disease Progression among Argentinean Seroconverters
(2014) Coloccini, Romina; Dilernia, Dario; Ghiglione, Yanina; Turk, Gabriela; Laufer, Natalia; Rubio, Andrea; Socias, Maria E.; Figueroa, Maria Ines; Sued, Omar; Cahn, Pedro; Salomon, Horacio; Mangano, Andrea; Pando, María Angeles
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) and disease progression within the first year. Methods Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing. Results Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07. Conclusion Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level.
Improving care for women living with HIV: initial outcomes of an integration experience
(2012) Fink, Valeria; Zurita, Daniela; Tejo, Marta; Perez, Hector; Cesar, Carina; Figueroa, Maria Ines; Patterson, Patricia; Sued, Omar; Cahn, Pedro
Background Women living with HIV are at higher risk of developing HPV-related diseases. Albeit they are systematically referred for cervical cancer screening, difficulties in obtaining timely appointments are the main barrier for an adequate gynecological care. In our unit, according to a previous survey, 67% of women reported this problem. Therefore, in January 2011 the integration of HIV and gynecological care was sought through the provision of gynecological care within the Infectious Diseases Unit in our hospital. Methods A weekly specific clinic for women living with HIV cared by HIV and gynecological specialists was implemented. Appointments are given at the HIV clinic, with no need of referral. Pap smear and colposcopy are offered in the same place. Data are collected through standardized forms. Baseline data from the first hundred patients referred are presented. Results Ninety-six women were assisted. Median age was 40 years (IQR 36–46.5). Median time from HIV diagnosis was 10.6 years (IQR 4.9–16.4). 82% patients were on HAART. Median CD4 cell count was 473 cells/cc (IQR: 287–614) and 49% had viral load<50. 48% lacked a gynecological control for the last 2 years. 24% had been previously diagnosed and/or treated for HPV-related pathology. Cervical Pap smear results (n=94): 59% were negative; 20% had LGSIL and 2% had HGSIL. Of those diagnosed with SIL, 29% had history of HPV-related lesions. Of note, 23% had infections or inflammatory results. Clinically significant abnormal colposcopies were seen in 21/93 (23%) patients. Of those, 30% were diagnosed SIL in the Pap smear. Conclusions Integrating the gynecologist with the ID Unit allowed women living with HIV easier access to gynecological control. The high number of abnormalities in the Pap smears detected in this pilot study reinforces the need of improving cervical cancer screening for prevention and early treatment through integrated approaches.
Inflammatory biomarker levels over 48 weeks with dual vs triple lopinavir/ritonavir-based therapy: Substudy of a randomized trial
(2019-09-06) Tan, Darrell HS; Rolón, María José ; Figueroa, Maria Ines; Sued, Omar; Gun, Ana; Kaul, Rupert; Raboud, Janet M; Szadkowski, Leah; Hull, Mark W; Walmsley, Sharon L; Cahn, Pedro
Background Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults. Methods This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count. Results Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm3. Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels. Conclusions In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted.
Lopinavir/ritonavir en nuevas estrategias de tratamiento antirretroviral de inicio
(2014) Rolón, María José; Figueroa, Maria Ines; Sued, Omar; Cahn, Pedro
La combinación de 2 inhibidores de la transcriptasa inversa análogos de nucleósidos (ITIAN) con 1 inhibidor de la transcriptasa inversa no análogo de nucleósidos (ITINAN) o con un inhibidor de la proteasa (IP) ha sido el tratamiento antirretroviral (TAR) de elección por más de 17 años, según la evidencia derivada de estudios aleatorizados controlados y de datos epidemiológicos. Entre los temas sin resolver se destacan la toxicidad causada por los ITIAN, particularmente los análogos timidínicos, y la posibilidad de resistencia cruzada que puede afectar a tratamientos subsiguientes. Con la aparición de nuevos fármacos antirretrovirales, de mayor comodidad posológica y menor toxicidad, se han comenzado a evaluar estrategias innovadoras como la biterapia para el TAR de inicio en pacientes vírgenes de tratamiento ARV, con el objetivo de prevenir la toxicidad a largo plazo y favorecer la adherencia al tratamiento. Si bien hay resultados alentadores, algunas combinaciones no han mostrado resultados satisfactorios. Las estrategias con resultados favorables hasta la fecha se observaron con regímenes basados en lopinavir/ritonavir (LPV/r) 2 veces al día, los estudios PROGRESS (LPV/r + raltegravir) y GARDEL (LPV/r + lamivudina) y con la combinación de darunavir y raltegravir (estudio NEAT 001), aunque en este último estudio se observó una mayor tendencia (estadísticamente no significativa) de fallo virológico en la rama dual. Los mismos fundamentan el uso de regímenes ahorradores de ITIAN con 2–3 agentes totalmente activos para los pacientes VIH+ vírgenes de TAR de gran actividad. Estudios recientes aportaron evidencias para el uso de regímenes ahorradores de ITIAN en pacientes infectados por VIH con fracaso a su primer TAR basado en ITINAN. Esta revisión se limitará a las estrategias innovadoras basadas en LPV/r en TAR de inicio.
Macrophage HIV-1 infection in duodenal tissue of patients on long term HAART
(2010) Zalar, Alberto; Figueroa, Maria Ines; Ruibal-Ares, Beatriz; Baré, Patricia; Cahn, Pedro; Bracco, Maria Marta; Belmonte, Liliana
Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis. Since the role of intestinal macrophages as viral reservoirs during chronic HIV-1 infection has not been elucidated, we investigated the effects of successful therapy on intestinal HIV-1 persistence. Intestinal macrophage infection was demonstrated by the expression of p24 antigen by flow cytometry and by the presence of proviral DNA, assessed by PCR. Proviral DNA was detected in duodenal mucosa of HIV-infected patients under treatment with undetectable plasma viral load. These findings confirm that intestinal macrophages can act as viral reservoirs and permit HIV-1 production even after viral suppression following antiretroviral therapy.
Prueba piloto de validación del método portátil PIMA para el recuento de células CD4 en comparación con la citometría de flujo.
(2015-04) Sued, Omar; Salgado, Pablo; Picchio, Camila; Figueroa, Maria Ines; Socias, Maria E.; Cando, Osvaldo; Díaz, Liliana; Hermes, Ricardo; Pérez, Héctor; Cahn, Pedro
Objetivo: comparar la metodología PIMA con la citometría de flujo convencional para el recuento de linfocitos CD4 en pacientes con infección por HIV. Métodos: se realizaron determinaciones pareadas en sangre venosa de pacientes con HIV y se comparó la correlación entre ambos resultados. Resultados: se realizaron 223 determinaciones en forma pareadas. La concordancia fue muy buena, con una correlación lineal de Pearson de 0,974, correlación por rangos de Spearman de 0,971 y con un coeficiente de determinación lineal (R cuadrado) de 0,949 (p < 0,01). El coeficiente de correlación intraclases para las medidas individuales fue de 0,965 (IC 95 % 0,926-0,980) y para medidas promedio 0,982 (IC95 % 0,961-0,990). El coeficiente de variación para medidas duplicadas fue bajo siendo 11,4 %. Discusión: este estudio demuestra una buena correlación entre la determinación de células CD4 con el sistema PIMA frente a la citometría de flujo y apoya el uso de estas metodologías donde no hay acceso a citometría convencional.
Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression
(2015) Falivene, Juliana; Ghiglione, Yanina; Laufer, Natalia; Socias, Maria E.; Holgado, Maria Pia; Ruiz, Maria; Maeto, Cynthia; Figueroa, Maria Ines; Giavedoni, Luis D.; Cahn, Pedro; Salomon, Horacio; Sued, Omar; Turk, Gabriela; Gherardi, María Magdalena
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 percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.

Browsing by Author "Figueroa, Maria Ines"

Results Per Page

Sort Options