Browsing by Author "Sued, Omar"
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Item A dynamic interplay of circulating extracellular vesicles and galectin-1 reprograms viral latency during HIV-1 infection(2019) Rubione, Julieta; Duette, Gabriela; Perez, Paula; Pereyra Gerber, Pablo; Salido, Jorge; Cagnoni, Ana; Guzman, Laura; Adamczyk, Ariel; Sued, Omar; Ghiglione, Yanina; Laufer, Natalia; Mariño, Karina; Rabinovich, Gabriel; Ostrowski, MarioHIV-positive individuals on antiretroviral therapy(art) have detectable cell-associated unspliced (ca-Us) HIV rNain cD4+ t-cells from blood which varies with time. additionally, werecently showed that circadian transcription factors, circadian Loco-motor output cycles Kaput (cLocK) and brain and Muscle arnt-likeprotein-1 (bMaL1), bind to the HIV Ltr and increase HIV transcrip-tion. We hypothesised that circadian rhythms exert transcriptionalcontrol on latent HIV.Item A global call for action to include gender in research impact assessment(2016-07-19) Ovseiko, Pavel V; Greenhalgh, Trisha; Adam, Paula; Grant, Jonathan; Hinrichs-Krapels, Saba; Graham, Kathryn E; Valentine, Pamela A; Sued, Omar; Boukhris, Omar F; Al Olaqi, Nada M; Al Rahbi, Idrees S; Dowd, Anne-Maree; Bice, Sara; Heiden, Tamika L; Fischer, Michael D; Dopson, Sue; Norton, Robyn; Pollitt, Alexandra; Wooding, Steven; Balling, Gert V; Jakobsen, Ulla; Kuhlmann, Ellen; Klinge, Ineke; Pololi, Linda H; Jagsi, Reshma; Lawton Smith, Hele; Etzkowitz, Henry; Nielsen, Mathias W; Carrion, Carme; Solans‐Domènech, Maite; Vizcaino, Esther; Naing, Lin; Cheok, Quentin HN; Eckelmann, Baerbel; Simuyemba, Moses C; Msiska, Temwa; Declich, Giovanna; Edmunds, Laurel D; Kiparoglou, Vasiliki; Buchan, Alison MJ; Williamson, Catherine; Lord, Graham M; Channon, Keith M; Surender, Rebecca; Buchan, Alastair MGlobal investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia and Europe – argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.Item A Novel Educational Strategy Targeting Health Care Workers in Underserved Communities in Central America to Integrate HIV into Primary Medical Care(2012) Flys, Theresa; González, Ricardo; Sued, Omar; Suarez Conejero, Jose; Kestler, Eduardo; Sosa, Nelson; McKenzie-White, Jane; Monzon, Irma Irene; Torres, Carmen; Page, KathleenBackground: Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs). We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. Methods: The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. Results: Of 258 initially active participants, 225 (225/258=87.2%) successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85%) attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p<0.001). The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p<0.001). A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills. Conclusion: This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills acquired through the process, and could continue working within their underserved communities while participating in the online component and then implement interventions that successfully converted theoretical knowledge to action to improve integration of HIV care into primary care.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.Item A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care(2022-06) Sued, Omar; Cecchini, Diego; Rolón, María José; Calanni, Liliana; David, Daniel; Lupo, Sergio; Cahn, Pedro; Cassetti, Isabel; Weiss, Stephen M.; Alcaide, Maria Luisa; Rodriguez, Violeta J.; Mantero, Alejandro; Jones, Deborah L.Background Patients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina. Methods Regional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient–provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350. Findings Participants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = -0·095, p = 0·027), and self-efficacy (B = 0·063, p = 0·001), suggesting the intervention was associated with improved patient–provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy. Interpretation These findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted.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, OmarBackground: 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.Item Acceptability of HIV Pre-exposure Prophylaxis (PrEP) Among People Who Inject Drugs (PWID) in a Canadian Setting(2015) Escudero, Daniel; Kerr, Thomas; Wood, Evan; Nguyen, Paul; Lurie, Mark; Sued, Omar; Marshall, BrandonA recent clinical trial provided evidence that pre-exposure prophylaxis (PrEP) has the potential to prevent HIV infection among people who inject drugs (PWID). We examined willingness to use PrEP among HIV-negative PWID in Vancouver, Canada (n = 543) to inform PrEP implementation efforts. One third (35.4 %) expressed willingness to use PrEP, with adjusted models indicating that younger age, no regular employment, requiring help injecting, engaging in sex work, and reporting multiple recent sexual partners were positively associated with willingness to use PrEP. Although willingness to use PrEP was low, PrEP was acceptable to some PWID at heightened risk for HIV infection.Item Acute HIV Seroconversion Presenting with Active Tuberculosis and Associated with High Levels of T-Regulatory Cells(2011) Sued, Omar; Quiroga, Maria F.; Socias, Maria E.; Turk, Gabriela; Salomon, Horacio; Cahn, PedroA patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients.Item Acute meningoencephalitis due to human immunodeficiency virus type 1 infection in 13 patients: Clinical description and follow-up(2008) Villar del Saz, Sergi; Sued, Omar; Falcó, Vicenç; Agüero, Francisco; Crespo, Manuel; Pumarola, Teresa; Curran, Andrea; Gatell, Jose; Pahissa, Alberto; Miro, Jose M.; Ribera, EstebanThe objective of this study is to describe a series of cases of severe meningitis caused by human immunodeficiency virus type 1 (HIV-1) occurring during primary infection or after antiretroviral treatment interruption. In an observational cohort study, 13 patients with clinical diagnosis of meningitis or meningoencephalitis were reviewed. Ten cases occurred during primary HIV-1 infection and 3 after antiretroviral therapy (ART) withdrawal. Demographic parameters, clinical presentation and outcome, and laboratory and cerebrospinal fluid (CSF) parameters were recorded. The risk factor for HIV-1 infection acquisition was sexual transmission in all cases. The most frequent systemic symptoms were fever (12/13) and headeache (9/13). Among neurologic symptoms, focal signs appeared in seven patients (53.8%), confusion in six (46.2%), and agitation in five (38.5%). The median CD4 cell count was 434 cells/mm3. In all cases, CSF was a clear lymphocytaire fluid with normal glucose levels. Cranial computerized tomography was performed in seven patients, with a normal result in all of them; brain magnetic resonance in eight patients was normal in five cases and showing cortical atrophy, limbic encephalitis, and leptomeningeal enhancement in one patient each. The electroencephalographs (EEG) just showed diffuse dysfunction in three cases. ART was started in 11 patients. HIV RNA load at 12 months was <50 copies/ml in all treated patients. The 13 patients recovered without neurologic sequela. Meningitis or meningoencephalitis during primary HIV-1 infection or after ART cessation are unusual but sometimes a life-threatening manifestation. Although all patients tend to recover and the necessity of ART is not well established, some data suggest its potential benefit in these patients.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, DamianBackground 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.Item Assessing the Underestimation of HIV Risk Infection Among Young Men Who Have Sex with Men in Argentina(2022-11) Feijoo-Cid, Maria; Fernández-Cano, María Isabel; Zalazar, Virginia; Moriña Soler, David; García-Sierra, Rosa; Arreciado Marañón, Antonia; Sued, OmarThe aim of this study is to describe the discordance between the self-perceived risk and actual risk of HIV among young men who have sex with men (YMSM) and its associated "factors. An online, cross-sectional study was conducted with 405 men recruited from an Argentinian NGO in 2017. Risk discordance (RD) was defined as the expression of the underestimation of risk, that is, as a lower self-perception of HIV risk, as measured with the Perceived Risk of HIV Scale, than the current risk of HIV infection, as measured by the HIV Incidence Risk Index. Multivariate logistic regression models were used to analyze the associations between the RD and the explanatory variables. High HIV risk was detected in 251 (62%), while 106 (26.2%) showed high self-perceived risk. RD was found in 230 (56.8%) YMSM. The predictors that increased RD were consistent condom use with casual partners (aOR = 3.8 [CI 95:1.5–11.0]), the use of Growler to meet partners (aOR = 10.38 [CI 95:161–121.94]), frequenting gay bars (aOR = 1.9 [95% CI:1.1–3.5]) and using LSD (aOR = 5.44 [CI 95:1.32–30.29]). Underestimation of HIV risk in YMSM is associated with standard HIV risk behavior and modulated by psychosocial aspects. Thus, prevention campaigns aimed at YMSM should include these factors, even though clinical practice does not. Health professionals should reconsider adapting their instruments to measure the risk of HIV in YMSM. It is unknown what score should be used for targeting high-risk YMSM, so more research is needed to fill this gap. Further research is needed to assess what score should be used for targeting high-risk in YMSM.Item Avances en el diagnóstico y tratamiento de la infección aguda por el VIH-1(2004) Miro, Jose M.; Sued, Omar; Plana, Marta; Pumarola, Tomas; Gallart, TeresaSegún la Organización Mundial de la Salud (OMS) cada día se infectan en el mundo unas 14.000 personas. Sin embargo, en pocos casos el diagnóstico se realizará durante la fase aguda de la infección por el virus de la inmunodeficiencia humana (VIH). La infección aguda por el VIH es el período comprendido entre la entrada del VIH en el organismo y la seroconversión completa, definida por una prueba de Western blot positiva. Este período dura aproximadamente 30 días y la mayoría de veces (40-90%) se acompaña de manifestaciones clínicas banales (fiebre, exantema, faringitis, úlceras en mucosas entre otras), de 2 semanas de duración, que se pueden confundir con otros procesos infecciosos comunitarios, entre ellos la mononucleosis infecciosa. El diagnóstico microbiológico se realiza por la ausencia de anticuerpos en plasma (prueba de análisis de inmunoabsorción ligado a enzimas [ELISA] negativa) y la presencia de una carga viral (CV) del VIH en plasma positiva (> 10.000 copias/ml). El diagnóstico de la infección aguda por el VIH es muy importante por varias razones: a) epidemiológicas, es el período con las mayores tasas de transmisión de la infección por el VIH y permite conocer el patrón de crecimiento de la epidemia y la tasa de transmisión de cepas resistentes a los antirretrovirales, que en España es del 10%; b) inmunopatológico, ya que es una oportunidad única para estudiar los mecanismos virológicos, inmunológicos, y genéticos implicados en la transmisión y patogenia de esta enfermedad; y c) terapéutico, ya que el inicio del tratamiento antirretroviral en esta fase podría modificar la historia natural de esta infección. Sin embargo, este es un tema controvertido y en la actualidad la mayoría de comités de expertos sólo recomiendan el tratamiento si se pueden incluir los pacientes en ensayos clínicos o si las manifestaciones clínicas son graves o duraderas.Item Avances en la construcción del Inventario de Estigma relacionado con el VIH (IE-VIH) en Buenos Aires, Argentina(2018-05) Radusky, Pablo; Zalazar, Virginia; Aristegui, Ines; Sued, Omar; Mikulic, Isabel MaríaLa expresión del estigma relacionado con el VIH, siendo culturalmente determinada, ha sufrido cambios a través de las décadas, asumiendo formas más sutiles, aunque igualmente perjudiciales. Por consiguiente, con el fin de medir este constructo, deben ser desarrollados nuevos instrumentos más actualizados y que capturen sus particularidades en contextos específicos. Tres dimensiones del estigma son reconocidas por los principales marcos teóricos: internalizado, anticipado y experimentado. Los objetivos de este estudio fueron explorar el funcionamiento de un conjunto inicial de ítems de un nuevo instrumento para medir estigma, obtener evidencia de confiabilidad y validez del instrumento y describir los niveles de estigma en personas con VIH adultas del Área Metropolitana de Buenos Aires (AMBA). Cinco expertos evaluaron la claridad, relevancia y validez de contenido de 88 reactivos preliminares. Una versión depurada de 77 ítems fue administrada a una muestra piloto. El análisis estadístico incluyó el análisis descriptivo de los ítems, alfas de Cronbach para establecer la confiabilidad y correlaciones con la Escala de Estigma de VIH, para verificar la validez de criterio. La muestra final consistió en 46 personas con VIH, adultas, residentes en el AMBA (67% hombres, 31% mujeres y 2% mujeres transgénero). La media de edad fue de 41 años (DE = 10.68). Cincuenta ítems con adecuada asimetría, curtosis y correlación ítem-total fueron conservados. Las escalas mostraron buena confiabilidad: Internalizado.86; Anticipado = .85 y Experimentado = .86. Cada escala correlacionó positiva y significativamente con su criterio. Se hallaron niveles más elevados de estigma anticipado, que de estigma internalizado y experimentado. Este nuevo instrumento diseñado para medir estigma relacionado con el VIH considerando sus particularidades locales, ha demostrado adecuada confiabilidad y validez, en esta primera etapa de su construcción. La etapa siguiente consistirá en un análisis factorial con una muestra de mayor tamaño con el fin de incrementar la evidencia de validez.Item Behçet's disease in an HIV-1-infected patient treated with highly active antiretroviral therapy(2006) Gómez-Puerta, Jose A.; Espinosa, Gerard; Miro, Jose M.; Sued, Omar; Llibre, Josep M.; Cervera, Ricard; Font, JoanBehcet’s disease is a systemic vasculitis of unknown etiology, characterized by recurrent oral and genital ulcers and uveitis. In addition, cutaneous, articular, neurologic, intestinal, pulmonary, urogenit tal and vascular manifestations have been observed in these patients [1]. Since the introduction of protease inhibitor-based antiretroviral therapy in 1996, the natural history of human immunodeficiency virus infection changed dramatically, with a decrease in disease progression and mortality. Simultaneously, a wide variety of autoimmune diseases emerged in this group of patients although the number of reports of HIV patients with Behcet’s disease seems to remain stable [2]. The diagnosis of Behcet’s disease in HIV pat tients may be difficult to establish, mainly because some clinical manifestations of infections related or not with HIV may mimic the clinical features of Behcet’s. We describe here an HIV-infected patient who developed Behcet’s disease 10 years after contracting HIV infection. In addition, we review the literature and describe the clinical characteristics of patients with this associationItem Bioinformatic analysis of post-transmission viral readaptation in Argentine patients with acute HIV-1 infection(2020-07) Damilano, G; Sued, Omar; Satorres, S; Ruiz, Maria; Ghiglione, Y; Guzman, F; Turk, Gabriela ; Quiroga, F; Cahn, Pedro; Salomon, Horacio; Dilernia, DarioDuring 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 primary HIV infection and 8 subjects that were the HIV positive partner resulting in 8 transmission pairs. Genotyping of the genetic polymorphisms of HLA class I A and B was performed using PCR-SSOP. Viral RNA extraction was from plasma. 570 single Gag-gene amplifications were obtained by limiting-dilution RT-PCR. Epitope prediction was performed with NetMHC CBS prediction server for the 19 HLA-A and single bondB alleles. Cytotoxic response prediction was performed by using the IEDB Analysis Resource. From our results, we deduce that the transmitted CTL / gag escape frequency in the founder virus was at least double compared to the post-transmission events. Additionally, by means of an algorithm that combines these frequencies, we observed that the founder viruses better adapted to the HLA A / B alleles of the recipient could contribute to a greater progression of the infection. Our results suggest that there is a large adaptation of HIV-1 to the HLA A / B alleles prevalent in our population. However, despite this adaptive advantage, the virus needs to make “readjustments” through new escape and compensatory mutations. Interestingly, according to our results, this readaptation could have a role in the progression of the infection.Item Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?(2018-01-13) Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, Maria; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomon, Horacio ; Giavedoni, Luis D; De los Ángeles Pando, María; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, OmarProgression 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+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.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, PedroAntecedentes: 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.Item Boosting HIV Treatment Options: Good News, New Challenges(2013) Cahn, Pedro; Sued, OmarFor >15 years, ritonavir (RTV) has been the only pharmacokinetic enhancer (ie, booster) for human immunodeficiency virus (HIV) protease inhibitors. The development of cobicistat (COBI) promises to provide an alternative to RTV without direct antiviral effects of its own. COBI, a potent cytochrome P450 3A (CYP3A) inhibitor recently approved by the Food and Drug Administration (FDA) for use in a single-tablet regimen of elvitegravir/COBI/emtricitabine(FTC)/tenofovir disoproxil fumarate (TDF), is currently being studied in phase 3 trials as booster of other antiretroviral drugs. In vitro studies demonstrate that COBI, unlike RTV, is a weak inhibitor for CYP2D6 and does not have inhibitory effects on other CYP isoforms (ie, CYP1A2, CYP2C09, and CYP2c19), making pharmacologic interactions more predictable [1]. COBI also seems to have less impact than RTV on normal adipocyte functions, such as lipid accumulation and/or response to insulin, which may offer the potential for fewer adverse biochemical effects relative to RTV [2]. In addition, the better solubility of COBI allows creation of a tablet formulation and coformulations that might foster the availability of other single-tablet regimens. In this issue of the Journal, Gallant et al report the 48-week results of a study comparing COBI with RTV as a pharmacoenhancer for atazanavir (ATV) plus FTC/TDF in 698 treatment-naive HIV type 1 (HIV-1)–infected patients. Study subjects were recruited in the United States, the Dominican Republic, Mexico, Thailand, Portugal, Germany, the United Kingdom, Italy, and Switzerland and were randomly assigned in a 1:1 ratio to receive COBI or RTV. Most of the participants (60%) were white, and similar to other large trials, the proportion of women (17%) was low. Twenty-four percent reported Hispanic/Latino ethnicity. The study allowed the inclusion of individuals with active hepatitis, with hepatitis B present in 3.6% of patients and hepatitis C in 5.3%. The immunologic status of the patients was relatively good, with 48% having CD4+ T-cell count of >350 cells/mL, reflecting the latest recommendations for treatment initiation [3]. Randomization was stratified by viral load, with 39.7% of patients having >100 000 HIV RNA copies/mL at baseline. Of the 692 patients who initiated treatment with the study medication, 344 were in the COBI arm and 348 were in the RTV arm. At 48 weeks, COBI-boosted ATV was shown to be virologically noninferior to RTV-boosted ATV, with 293 patients (85.2%) and 304 patients (87.4%) in the COBI and RTV arms, respectively, achieving an HIV-1 RNA load of <50 copies/mL, in accordance with the FDA snapshot intention-to-treat analysis (observed difference, −2.2% [95% confidence interval, −7.4% to 3.0%]). Mean increases in CD4+ T-cell counts were also similar in the COBI and RTV groups (+213 cells/mm3 and +219 cells/mm3, respectively at week 48). Favorable responses were comparable in patients with a high viral load (86.4% in the COBI group vs 86.0% in the RTV group). Of the 95 subjects who were not reported as having achieved virologic success, treatment in 34 was defined as virologic failure (5.8% and 4% in the COBI and RTV arms, respectively), but this small difference was not statistically significant. The remaining 61 patients discontinued the protocol because of adverse events or other reasons, despite having undetectable viral loads. No major tolerability issues were reported. Gastrointestinal adverse events were not statistically different between the COBI and RTV groups, with similar rates of nausea (17.7% and 16.4%, respectively), vomiting (7.3% and 4.6%, respectively), or diarrhea (15.4% and 20.4%, respectively), but only 2 patients (1 in each arm) had to stop treatment because of gastrointestinal complaints. A similar tolerability profile was shown in another study comparing elvitegravir/COBI/FTC/TFV with COBI-boosted ATV [4]. The most common adverse events were those related to an elevated bilirubin level, a well-known side effect of ATV use, and included jaundice and scleral icterus, reaching rates of 40.7% and 36.2% in the COBI and RTV groups, respectively, although these rarely led to treatment discontinuation (3.5% in the COBI arm and 3.2% in the RTV group). A small increase in serum creatinine level, usually within the first 8 weeks of treatment, was observed in both arms (median change from baseline, + 0.13 mg/dL vs + 0.09 mg/dL; P < .001) with a concomitant decrease in the estimated glomerular filtration rate (eGFR; median change, −12.9 mL/min vs −9.1 mL/min; P < .001), although renal adverse events leading to treatment discontinuation were rarely reported. Only 6 patients (1.7%) in the COBI arm and 5 patients (1.4%) in the RTV group stopped receiving study drugs, and no patient required dialysis. Of note, in the COBI arm most of the patients (5 of 6) who stopped treatment had laboratory findings consistent with proximal tubulopathy, such as hypophosphatemia, proteinuria, or normoglycemic glycosuria, that resolved or improved after treatment discontinuation, whereas in the RTV group most of the patients (3 of 5) who stopped treatment showed an increase in their serum creatinine level without evidence of tubular dysfunction. Renal safety emerged as a potential concern early in the development of COBI, as increases in the serum creatinine level were observed in patients treated with COBI-containing regimens. This increase is not associated with an actual decrease in the actual GFR; instead, COBI drives a reduction in the eGFR, because of an inhibition of the secretion of creatinine, without affecting the actual GFR [5]. An increase of ≥0.4 mg/dL from baseline was proposed for distinguishing the effect of cobicistat on the serum creatinine level from genuine renal dysfunction [6]. In the study by Gallant et al, changes in renal measurements were observed in both groups, and abnormalities reverted after discontinuation of study drugs. It has been previously reported that TDF, which was used in both study arms, can cause proximal tubulopathy [7]. Observational studies have also shown that this toxicity might be more frequent when TDF is associated with ritonavir-boosted protease inhibitors [8]. Experiments in vitro [9] have shown that COBI increases the intestinal absorption of protease inhibitors and TDF. The clinical relevance of these findings remains unclear and deserves further research. Of note, although the number of patients who discontinued participation in this phase 3 study because of renal events was small, proximal tubulopathy features were observed in 5 of 6 subjects in the COBI arm and in 2 of 5 subjects in the RTV arm. During COBI use, routine renal monitoring (eg, urine protein level, urine glucose level, serum creatinine level, and calculated creatinine clearance rate) every 6 months (as recommended for patients receiving TDF) is advised for early identification of tubulopathy. A tenofovir prodrug in development, tenofovir alafenamide fumarate (TAF), formerly known as GS-7340, has antiviral potency similar to or exceeding that of TDF. It was designed to reach higher concentrations in cells and lymphoid tissues, with lower levels in blood serum, which may minimize its detrimental effects on kidneys and bones [10]. Studies to evaluate the efficacy of TAF in a tablet coformulated with elvitegravir/COBI and FTC are underway [11]. How this new drug will interact with COBI remains a research question. The results of the study by Gallant et al validate those reported by Elion et al in the phase 2 study of COBI versus RIT [12]. In that study, 89 patients were randomly assigned in a 2:1 ratio to the ATV/COBI arm. Through week 48, both groups achieved and maintained similar rates of virologic suppression and similar CD4+ T-cell count increases. Similarly, the most common toxicity was also driven by high bilirubin levels. Actually, slightly higher bilirubin levels in the COBI arm were found in the studies by Elion et al and Gallant et al; it was hypothesized that differences between COBI and RTV in the affinity for off-target metabolic enzymes could be implicated, although levels of ATV measured in a subsample of patients were not significantly different between arms. Gilead has submitted a New Drug Application to the FDA for marketing approval of cobicistat as a boosting agent for darunavir and ATV [13]. Studies of coformulations with these drugs are ongoing [14]. Of note, Gilead, the COBI patent holder, signed an agreement with the Medicines Patent Pool to transfer the manufacturing technology to Indian companies in order to produce generic versions of this drug, making it potentially available in 102 low- and middle-income countries [15]. In conclusion, this phase 3 study shows that COBI-boosted ATV has high a efficacy, a good tolerability profile, and is noninferior to RTV-boosted ATV. Its potential role in novel ART combinations will depend on the confirmation of its promising data as a new boosting agent, cost comparisons to ritonavir, and the availability of new coformulations. HIV caregivers now have a new tool for managing their patients, as well as a new challenge in understanding the implications of changes in results of renal function tests.Item Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women(2021-08) Landovitz, Raphael; Donnell, Deborah J.; Clement, Meredith; Hanscom, Brett; Cottle, Leslie; Coelho, Lara; Cabello, Robinson; Chariyalertsak, Suwat; Dunne, Eileen F.; Frank, Ian; Gallardo-Cartagena, Jorge A.; Gaur, Aditya H.; Gonzales, Pedro; Tran, Ha V.; Hinojosa, Juan C.; Kallas, Esper; Kelley, Colleen F.; Losso, Marcelo H.; Valdez Madruga, J.; Middelkoop, Keren; Phanuphak, Nittaya; Santos, Breno R.; Sued, Omar; Valencia Huamaní, Javier; Overton, Edgar T.; Swaminathan, Shobha; del Rio, Carlos; Gulick, Roy M.; Richardson, Paul; Sullivan, Philip; Piwowar-Manning, Estelle M.; Marzinke, Mark; Hendrix, Craig; Li, Maoji; Wang, Zhe; Marrazzo, Jeanne; Daar, Eric; Asmelash, Aida; Brown, Todd T.; Anderson, Peter; Eshleman, Susan H.; Bryan, Marcus; Blanchette, Cheryl; Lucas, Jonathan; Psaros, Christina; Safren, Steven A.; Sugarman, Jeremy; Scott, Hyman; Eron, Joseph; Fields, Sheldon D.; Sista, Nirupama D.; Gomez, Kailazarid; Jennings, Andrea; Kofron, Ryan M.; Holtz, Timothy H.; Shin, Katherine; Rooney, James F.; Smith, Kimberly; Spreen, William; Margolis, David; Rinehart, Alex; Adeyeye, Adeola; Cohen, Myron; McCauley, Marybeth; Grinsztejn, BeatrizBACKGROUND Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate–emtricitabine (TDF–FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF–FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF–FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS CAB-LA was superior to daily oral TDF–FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.)Item Características clinicoepidemiológicas y tendencias en el tratamiento antirretroviral de una cohorte de pacientes con infección por el virus de la inmunodeficiencia humana. Cohorte PISCIS(2005-04) Jaén, Ángeles; Casabona, Jordi; Esteve, Anna; Miró, Jose M; Tural, Cristina; Ferrer, Elena; Riera, Melchor; Segura, Ferran; Force, Lluís; Sued, Omar; Vilaró, Josep; Masabeu, Àngels; García, Isabel; Dorca, Esther; Altès, Jordi; Navarro, Gemma; Podzamczer, Daniel; Villalonga, Concepción; Clotet, Bonaventura; Gatell, JoseFundamento y objetivo: Los objetivos de este estudio fueron describir el proceso de implementación de la cohorte PISCIS y las características clinicoepidemiológicas y las tendencias en el tratamiento antirretroviral (TARV) de los pacientes con infección por el virus de la inmunodeficiencia humana (VIH) incluidos desde 1998 hasta 2003. Pacientes y método: Estudio de cohorte prospectivo de pacientes con infección por el VIH de 16 años de edad o mayores atendidos en primera visita en 10 hospitales de Cataluña y uno de las Baleares. El análisis estadístico de las tendencias se realizó mediante el test de la *2 de Mantel. Resultados: Se incluyó a un total de 5.968 pacientes (edad media: 39,5 años; 75% varones) con un tiempo medio de seguimiento de 26,4 meses (13.130 personas-año). Del total, 2.763 fueron nuevos diagnósticos, en los que la vía de transmisión más frecuente fue la heterosexual (43%), seguida de la homosexual (31%). Se observó una tendencia significativamente creciente en la proporción de sujetos de edad inferior a 35 años e inmigrantes. Un 43% tenían una cifra de linfocitos CD4 inferior a 200 células/µl en la determinación más cercana al diagnóstico de la infección por el VIH. Del total, un 87% estaban en TARV en el año 2003. Entre los pacientes no tratados previamente que iniciaron pautas de TARV con 3 o más fármacos, se observó una disminución de las pautas que incluían inhibidores de la proteasa (del 85% en 1998 al 25% en 2003; p < 0,001), mientras que aumentaron otras que contenían inhibidores de la transcriptasa inversa no análogos y análogos de los nucleósidos. Conclusiones: Las cohortes de pacientes con infección por el VIH son viables en nuestro medio y tienen gran utilidad clínica y en salud pública. La vía de transmisión más frecuente entre los nuevos diagnósticos es la heterosexual, el retraso en el diagnóstico es elevado y las pautas de TARV han ido cambiando para adaptarse a las recomendadas por las guías.