Browsing by Author "Gun, Ana"

Now showing 1 - 12 of 12
  • Thumbnail Image
    Item
    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 At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis)=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1) and the remaining pts (11/13) achieved undetectable pVL and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.
  • Thumbnail Image
    Item
    Acceptability of dual HIV/syphilis rapid test in community- and home-based testing strategy among transgender women in Buenos Aires, Argentina
    (2021-02-03) Zalazar, Virginia; Frola, Claudia; Gun, Ana; Radusky, Pablo; Panis, Natalia k; Cardozo, Nadir F; Fabian, Solange; Duarte, Mariana I; Aristegui, Ines; Cahn, Pedro; Sued, Omar
    Background: Little is known of acceptability and feasibility of dual HIV and syphilis rapid tests in community- and home-based provider-initiated strategies among transgender women (TGW), in Latin America. Objectives were (1) to assess the acceptability of this strategy and, (2) to determine the percentage of positive results of HIV and syphilis, analyze the correlates of HIV or syphilis positive results, and measure the rates of effective referral and treatment completion among TGW. Methods: A multidisciplinary team tested 89 TGW in Buenos Aires. An acceptability survey was administered after the HIV/syphilis Duo test was used. All confirmed cases were referred for treatment initiation. Results: We found high levels of acceptability (98.8%) of this strategy among TGW. However, only 60.7% preferred simultaneous HIV and syphilis diagnosis test. Moreover, we found 9% of positive results of HIV, 51.7% of syphilis, and 3.4% of positive results for both infections. Only not being tested before was associated with an HIV positive result, and only low level of education was associated with a positive syphilis result. Among 8 TGW who tested positive for HIV, 37.5% (n = 3) started antiretroviral therapy. Of 46 who tested positive for syphilis, only 73.9% (n = 34) were effectively referred and from 23 who started treatment, only 39.1% completed it. Conclusions: Community- and home-based dual HIV and syphilis rapid test is a feasible and highly acceptable approach for this hard-to-reach population. Implementing similar strategies could improve screening uptake and accessibility. However, these results highlight the need to improve strategies for treatment uptake, in order to reduce morbidity and risk of onward transmission.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE
    (Fundación Huésped - Sociedad Argentina de Infectología, 2023-07) Figueroa, María Inés; Sued, Omar; Cesar, Carina; Patterson, Patricia; Yamamoto, Cleyton; Fink, Valeria; Luna, Norma; Camiro-Zúñiga, Antonio; Gun, Ana; Cahn, Pedro
    Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba- sado en INNTR.ClinicalTrials.gov, Número: NCT01829802. Método: Estudio piloto abierto, multicéntrico y aleatoriza- do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta- dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue- ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues- ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/μL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H). Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802.
  • Thumbnail Image
    Item
    Dolutegravir–lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study
    (2017-01-01) Cahn, Pedro; Rolón, María José; Figueroa, María Inés; Gun, Ana; Patterson, Patricia; Sued, Omar
    Introduction: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. Methods: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). Results: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686–36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296–517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180–462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients. Conclusions: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. ClinicalTrials.gov Identifier: NCT02211482.
  • Thumbnail Image
    Item
    Dual therapy (ritonavir boosted atazanavir+raltegravir) versus standard triple therapy (ritonavir boosted atazanavir+tenofovir/emtricitabine) in patients failing first line therapy: 48 week results from a randomized pilot study
    (2018-08) Sued, Omar; Figueroa, MI; Cesar, Carina; Patterson, Patricia; Yamamoto, C; Fink, N; Gun, Ana; Cahn, Pedro
    Background: Dual therapy has emerged as a novel concept in treatment optimization in naive and supressed HIV patients. This study aimed at exploring virological response, safety and inflammation markers of a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among patients failing first NNRTI-containing treatment. Methods & Materials: Randomized open label pilot study. Primary outcome measures were proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/uL) and proportion of subjects discontinuing due to adverse events (AEs) during the first 48 weeks. ClinicalTrials.gov Identifier: NCT01829802. Results: Out of 57 patients screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At baseline 80% males, 50% MSM, median age 38 years, CDC stage C:35%, Median pVL: 3.9 Log10, CD4: 289 cells/uL. At week 48, data from 32 participants (2 did not reach week 48 yet) showed virological response in 69% (n: 11/16) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% (DT) and 93% (TT) by per-protocol analysis (p = NS). CD4 cell count median change from baseline to week 48 was +119 and + 52 cell/uL in DT and TT, respectively. No deaths were recorded. Three SAEs occurred in 2 participants (pneumonia and stroke and, Belĺs paralysis), none related to study drugs. Eight Grade 2, probably drug-related AEs were observed: 1 in DT (gastrointestinal) and 7 in TT (5 gastrointestinal, 1 renal stone and 1 rash). Hyperbilirubinemia Grade 2/3 was seen in 77% in DT and 94% in TT, none requiring stopping ART. Two participants were discontinued due to loss of follow-up, one in each arm. Five participants had virological failure at W48, 4 in DT and 1 in TT, all with low pVL (52-589 copies/uL). One participant developed integrase resistance mutation and suppressed later on TT. Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Longitudinal characterization of HIV-1 pol-gene in treatment-naïve men-who-have-sex-with-men from acute to chronic infection stages
    (2021-12-07) Cevallos, Cintia; Culasso, Culasso; Modenutti, Carlos; Gun, Ana; Sued, Omar; Avila, María M; Flichman, Diego; Delpino, M Victoria; Quarleri, Jorge
    HIV-1 is characterized by its ability to mutate and recombine even at polymerase (pol) gene. However, pol-gene diversity is limited due to functional constraints. The aim of this study was to characterize longitudinally, by next-generation sequencing (NGS), HIV-1 variants based on pol-gene sequences, at intra- and inter-host level, from acute/early to chronic stages of infection, in the absence of antiretroviral therapy. Ten men who have sex with men (MSM) were recruited during primary infection and yearly followed for five years. Even after a maximum of a five-year follow-up period, the phylogenetic analysis of HIV-1 pol-gene sequences showed a host-defined structured pattern, with a predominance of purifying selection forces during the follow-up. MSM had been acutely infected by different HIV-1 variants mainly ascribed to pure subtype B, or BF recombinant variants and showed different genetic mosaicism patterns that last until the chronic stage, representing a major challenge for prevention strategies.
  • Thumbnail Image
    Item
    Retention among transgender women treated with dolutegravir associated with tenofovir/ lamivudine or emtricitabine in Argentina: TransViiV study
    (Plos, 2023-01) Frola, Claudia; Aristegui, Ines; Figueroa, María I.; Radusky, Pablo; Cardozo, Nadir; Zalazar, Virginia; Cesar, Carina; Patterson, Patricia; Fink, Valeria; Gun, Ana; Cahn, Pedro; Sued, Omar
    In Argentina, transgender women (TGW) have a high HIV prevalence (34%). However, this population shows lower levels of adherence, retention in HIV care and viral suppression than cisgender patients. The World Health Organization (WHO) recommends the transition to dolutegravir (DTG)-based regimens to reduce adverse events and improve adherence and retention. The purpose of this study was to determine retention, adherence and viral suppression in naïve TGW starting a DTG-based first-line antiretroviral treatment (ART) and to identify clinical and psychosocial factors associated with retention. We designed a prospective, open-label, single-arm trial among ART-naïve HIV positive TGW (Clinical Trial Number: NCT03033836). Participants were followed at weeks 4, 8, 12, 24, 36 and 48, in a trans-affirmative HIV care service that included peer navigators, between December, 2015 and May, 2019. Retention was defined as the proportion of TGW retained at week 48 and adherence was self-reported. Viral suppression at <50 copies/mL was evaluated using snapshot algorithm and as per protocol analysis. Of 75 TGW screened, 61 were enrolled. At baseline, median age was 28 y/o., HIV-1-RNA (pVL) 46,908 copies/mL and CD4+ T-cell count 383 cells/mm3. At week 48, 77% were retained and 72% had viral suppression (97% per protocol). The regimen was well tolerated and participants reported high adherence (about 95%). Eleven of the fourteen TGW who discontinued or were lost to follow-up had undetectable pVL at their last visit. Older age was associated with better retention. DTG-based treatment delivered by a trans-competent team in a trans-affirmative service was safe and well tolerated by TGW and associated with high retention, high adherence and high viral suppression at 48 weeks among those being retained.
  • Thumbnail Image
    Item
    Safe Treatment Interruptions in Patients With Nadir CD4 Counts of More Than 350 Cells/μL
    (2006-04-01) Krolewiecki, Alejandro J.; Zala, Carlos; Vanzulli, Claudia; Pérez, Héctor; Iannella, María del Carmen; Bouzas, María Belén; Gun, Ana; Valiente, José; Cassetti, Isabel; Cahn, Pedro
    Objective: To evaluate clinical, immunologic, and virologic performance of patients with nadir CD4 counts of >350cells/μL upon treatment interruption. Design: Randomized, open-label clinical trial of 48 weeks' duration. Methods: Patients on effective highly active antiretroviral therapy, with nadir CD4 counts of >350 cells/μL and peak viral loads of <50,000 copies/mL were randomized to continue therapy or to interrupt antiretroviral medication. End points for patients with treatment interruption were CD4 counts of <350 cells/μL, viral loads of >1 log above the pretherapy values, or clinical symptoms attributable to HIV, at which point treatment was restarted. In the continuation group, the end points were virologic failure, opportunistic infections, and treatment discontinuation due to toxicities. Results: Twenty patients were randomized to stop therapy and 16 patients to continue. Median CD4 counts at baseline were 643 cells/μL for the interruption group and 633 cells/μL for the continuation group. No end points were reached in the interruption group. By week 8, viral load returned to values comparable to those of pretherapy in all patients in the interruption group and remained stable until week 48. CD4 counts dropped in the interruption group (median loss of 156 cells/μL) at week 48. Significant decreases in venous lactate were observed in the interruption group. Conclusions: Treatment interruptions in patients with nadir CD4 counts of >350 cells/μL seem safe for at least 48 weeks. Pretherapy viral load appears as a valuable tool to predict its level at week 48.
  • Thumbnail Image
    Item
    The effect of protease inhibitor-based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART-naïve patients with HIV-infection
    (2020-12-17) Figueroa, MI; Camiro-Zuñiga, A; Belaunzaran-Zamudio, PF; Sierra Madero, J; Andrade Villanueva, J; Arribas, JR; Lama, JR; Cecchini, DM; Lopardo, G; Crabtree-Ramírez, B; Gun, Ana; Patterson, Patricia; VI, Fink; Sued, Omar; Cahn, Pedro
    Objectives To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. Methods We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann–Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. Results We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. Conclusion The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.
  • Thumbnail Image
    Item
    Use of darunavir and enfuvirtide in a pregnant woman
    (2009) Sued, Omar; Lattner, Julia; Gun, Ana; Patterson, Patricia; Abusamra, Lorena; Cesar, Carina; Fink, Valeria; Krolewiecki, Alejandro J.; Cahn, Pedro
    A 41-year-old pregnant woman with multiple virological failures started darunavir, enfuvirtide, zidovudine and lamivudine at week 28 of pregnancy. During week 38, the patient had a viral load <400 copies/mL and a CD4 count of 180 cells/mm(3) (13%). The child was found to be in good health, with negative HIV-polymerase chain reactions at birth, at two and at six months.