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Item High Willingness to Use HIV Pre-Exposure Prophylaxis Among Transgender Women in Argentina(2016-12-01) Zalazar, Virginia; Aristegui, Ines; Kerr, Thomas; Marshall, Brandon D L; Romero, Marcela; Sued, Omar; Socias, Maria E.Fil: Sued O. Fundación Huésped, Buenos Aires; ArgentinaItem HIV/AIDS prevention, care and treatment in the Region of the Americas: achievements, challenges and perspectives(2016-12) Pérez, Freddy; Ravasi, Giovanni; Figueroa J, Peter; Grinsztejn, Beatriz; Kamb, Mary; Sued, Omar; Ghidinelli, MassimoThe world has pledged within the Sustainable Development Goals to end the AIDS epidemic by 2030. In Latin America and the Caribbean in 2015 approximately 2.0 million people were living with HIV and an estimated 100 000 new infections occurred. Yet, significant progress has been made in the Region of the Americas over the past ten years in expanding access and coverage of HIV care and treatment and in achieving elimination of mother-to-child transmission of HIV and syphilis (1, 2). Regarding HIV prevention, and HIV stigma and discrimination new regional elimination targets have also been developed and endorsed (3). However, challenges still persist; among them, a 3% increase in the rate of new HIV infections in the Region between 2010 and 2015 (4). This special issue on HIV/AIDS prevention, care and treatment in the Region of the Americas: achievements, challenges and perspectives provides an opportunity to present the current response to HIV/AIDS in the Region with a focus on three main areas: HIV prevention, HIV care and treatment, and the elimination of mother-to-child transmission of HIV and congenital syphilis. A call for papers was issued in early 2016, and 12 articles were selected for publication—nine original research papers, one brief communication, one review, and one opinion and analysis article. The papers represent seven different countries as well as an overview of the Caribbean sub-region. A successful HIV prevention program requires a combination of structural, biomedical, and behavioral interventions that are mutually reinforcing, continually evaluated, and tailored to the needs and risks of specific key populations and others who are vulnerable to infection. Previous reports have shown the importance of combination prevention strategies (5). The special issue addresses this by focusing on HIV prevention strategies available for men who have sex with men in the United States (6), as well as the social vulnerability of transgender persons (7). Both papers highlight the need for tailored interventions that take into account local epidemiological contexts.Item Impact of reverse transcriptase resistance on the efficacy of TMC125 (etravirine) with two nucleoside reverse transcriptase inhibitors in protease inhibitor-naïve, nonnucleoside reverse transcriptase inhibitor-experienced patients: study TMC125-C227†(2008-11-27) Ruxrungtham, K; Pedro, RJ; Latiff, GH; Conradie, F; Domingo, P; Lupo, S; Pumpradit, W; Vingerhoets, JH; Peeters, M; Peeters, I; Kakuda, TN; De Smedt, G; Woodfall, B; on behalf of the TMC125-C227 study groupHIV-NAT, Thai Red Cross AIDS Research Center and Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailanItem Prevalence of cryptococcal infection among advanced HIV patients in Argentina using lateral flow immunoassay(2017-06-15) Frola, Claudia; Guelfand, Liliana; Blugerman, Gabriela; Szyld, Edgardo; Kaufman, Sara; Cahn, Pedro; Sued, Omar; Pérez, HéctorBackground Globally, Latin America ranks third among regions with most cases of AIDS related cryptococcal meningitis. In 2009, a lateral flow immunoassay (LFA) for the detection of cryptococcal antigen (CrAg) was developed as a potential point-of-care test for diagnosis of cryptococcal infection. In 2011 World Health Organizations recommended on CrAg screening for HIV positive persons with CD4 below 100 cells/μL, followed by preemptive fluconazole treatment. However, in Argentina no formal recommendations for CrAg screening have been issued. Methods HIV positive patients > = 18 years with advanced immunosuppression (CD4 counts ≤100 cells/μL within 3 months or WHO stage III/IV), who visited the hospital between April 1, 2014 and January 31, 2015, were included. The LFA was performed according to the manufacturer’s instructions on all serum samples. When CrAg detection was positive, a lumbar puncture was performed to rule out cryptococcal meningitis. Patients without evidence of meningeal involvement were treated with preemptive oral fluconazole in ambulatory care. Results We included 123 patients. Prevalence of CrAg-positivity was 8.1%. Among the 10 CrAg-positive patients, 6 had meningeal involvement detected through the CSF analysis (CSF India-ink testing, CSF CrAg and culture). The remaining 4 patients with positive CrAg received targeted preemptive treatment with oral fluconazole and were free of cryptococcal disease during the follow-up period. None of the 113 patients with a negative CrAg test result developed cryptococcal disease. Conclusions This is the first study in Argentina, to our knowledge, describing the prevalence of cryptococcosis and usefulness of CrAg screening. LFA provided early diagnosis to determine a high prevalence of CrAg in our hospital, and that screening for subclinical infection with preemptive antifungal treatment, prevented a substantial proportion of meningeal disease.Item The HIV care cascade in Buenos Aires, Argentina: results in a tertiary referral hospital(2016-12) Cesar, Carina; Blugerman, Gabriela; Valiente, José Antonio; Rebeiro, Peter; Sued, Omar; Fink, Valeria; Romero Soto, Mariana; Cillis, Roberto; Yamamoto, Cleyton; Falistocco, Carlos; Cahn, Pedro; Pérez, HéctorObjective: To determine rates of retention, antiretroviral therapy (ART) use, and viral suppression in an adult cohort from a public tertiary referral hospital in the city of Buenos Aires, Argentina. Methods: HIV-positive ART-naïve patients ≥ 18 years old starting care 2011-2013 contributed data until the end of 2014. Three outcomes were assessed in 2014: retention in care, ART use, and viral suppression. Patient characteristics associated with each outcome were assessed through logistic regression. Results: A total of 1 031 patients were included. By the end of 2014, 1.5% had died and 14.8% were transferred to a different center. Of the remaining 859 patients, 563 (65.5%) were retained in 2014. Among those retained, 459 (81.5%) were on ART in 2014. Of those 459 on ART, 270 (58.8%) were virologically suppressed. Younger age was associated with lower retention (OR (odds ratio): 0.67; 95% CI (confidence interval): 0.44-0.92 for ≥ 35 vs. < 35 years), but unrelated with ART use or viral suppression. Low CD4 count at first visit was associated with ART use (OR: 35.72 for CD4 < 200, 7.13 for CD4 200-499 vs. ≥ 500, P < 0.001) and with virologic suppression (OR: 2.17 for CD4 < 200, 2.46 for CD4 200-499 vs. ≥ 500, P: 0.023). Conclusions: Our hospital in Buenos Aires is still below the recommended 90-90-90 targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for ART use and viral suppression. We found a major gap in retention in care. Identifying younger age as being associated with worse retention will help in the design of targeted interventions.Item Clinical and public health implications of acute and early HIV detection and treatment: a scoping review(2017-06-28) Rutstein, Sarah E; Ananworanich, Jintanat; Fidler, Sarah; Johnson, Cheryl; Sanders, Eduard J; Sued, Omar; Saez-Cirion, Asier; Pilcher, Christopher D; Fraser, Christophe; Cohen, Myron S; Vitoria, Marco; Doherty, MegIntroduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. Results and discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.Item HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy—Results From the IeDEA Collaboration(2017-11-01) Jiamsakul, Awachana; Awachana, Azar; Althoff, Keri N; Cesar, Carina; Cortes, Claudia; Davies, Mary-Ann; Do, Viet Chau; Eley, Brian; Gill, John; Kumarasamy, Nagalingeswaran; Machado, Daisy Maria; Moore, Richard; Prozesky, Hans; Zaniewski, Elizabeth; Law, MatthewMachadoItem Expansion of CD25-Negative Forkhead Box P3-Positive T Cells during HIV and Mycobacterium tuberculosis Infection(2017-05-09) Angerami, Matías T; Suarez, Guadalupe V; Vecchione, María B; Laufer, Natalia; Ameri, Diego; Ben, Graciela; Perez, Hector; Sued, Omar; Salomon, Horacio ; Quiroga, María FTuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of “unconventional” CD4+CD25−FoxP3+ Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4+CD25+FoxP3+ Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg. Also, IL-10, TGF-β, IFN-γ production, and the suppressor capacity of uTregs were analyzed in cocultures with effector lymphocytes and compared with the effect of regulatory T cells (Tregs). We found diminished expression of CD39 and higher levels of PD1 on uTreg compared to cTreg in both HIV-TB and healthy donors (HD). In addition, uTreg and cTreg showed differences in maturation status in both HIV-TB and HD groups, due to the expansion of effector memory uTregs. Interestingly, both HIV-TB and HD showed a pronounced production of IFN-γ in uTreg population, though no significant differences were observed for IL-10 and TGF-β production between uTreg and cTreg. Moreover, IFN-γ+ cells were restricted to the CD39− uTreg population. Finally, when the suppressor capacity was evaluated, both uTreg and cTreg inhibited polyclonal T cell-proliferation and IFN-γ production in a similar extent. These findings suggest that uTregs, which are expanded during HIV-TB coinfection, exert regulatory functions in a similar way to cTregs despite an altered surface expression of Treg characteristic markers and differences in cytokine production.Item Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates(2017-11-03) Ruiz, Maria; Salido, Jimena; Abusamra, Lorena; Ghiglione, Yanina; Cevallos, Cintia; Damilano, Gabriel; Rodriguez, Ana María; Trifone, César; Laufer, Natalia; Giavedoni, Luis D; Sued, Omar; Salomon, Horacio ; Gherardi, María Magdalena; Turk, GabrielaAs the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV+-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV− donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.Item Physician-delivered motivational interviewing to improve adherence and retention in care among challenging HIV-infected patients in Argentina (COPA2): study protocol for a cluster randomized controlled trial(2018-07-24) Sued, Omar; Cassetti, Isabel; Cecchini, Diego; Cahn, Pedro; de Murillo, Lina Bofill; Weiss, Stephen M; Mandell, Lissa N; Soni, Manasi; Jones, Deborah LBackground “Challenging” HIV-infected patients, those not retained in treatment, represent a critical focus for positive prevention, as linkage to care, early initiation of antiretroviral therapy, adherence and retention in treatment facilitate viral suppression, thus optimizing health and reducing HIV transmission. Argentina was one of the first Latin American countries to guarantee HIV prevention, diagnosis and comprehensive care services, including antiretroviral medication, which removed cost and access as barriers. Yet, dropout occurs at every stage of the HIV continuum. An estimated 110,000 individuals are HIV-infected in Argentina; of these, 70% have been diagnosed and 54% were linked to care. However, only 36% have achieved viral suppression and 31% of those diagnosed delayed entry to care. To achieve meaningful reductions in HIV infection at the community level, innovative strategies must be developed to re-engage patients. Motivational Interviewing (MI) is a patient-centered approach and has been used by therapists in Central and South America to enhance motivation and commitment in substance use and risk reduction. Our pilot feasibility study utilized culturally tailored MI in physicians to target patients not retained in treatment in public and private clinics in Buenos Aires, Argentina. Results demonstrated that a physician-based MI intervention was feasible and effective in enhanced and sustained patient adherence, viral suppression, and patient-physician communication and attitudes about treatment among these patients at 6 and 9 months post baseline. Methods/design This clinical trial seeks to extend these findings in public and private clinics in four urban population centers in Argentina, in which clinics (n = 6 clinics, six MDs per clinic site) are randomized to experimental (physician MI Intervention) (n = 3) or control (physician Standard of Care) (n = 3) conditions in a 3:3 ratio. Using a cluster randomized clinical trial design, the study will test the effectiveness of a physician-based MI intervention to improve and sustain retention, adherence, persistence, and viral suppression among “challenging” patients (n = 420) over 24 months. Discussion Results are anticipated to have significant public health implications for the implementation of MI to re-engage and retain patients in HIV treatment and care and improve viral suppression through high levels of medication adherence. Trial registration ClinicalTrials.gov, ID: NCT02846350. Registered on 1 July 2016.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 Segurança e eficácia da terapia antirretroviral baseada em dolutegravir, na semana 48, em adultos coinfectados hiv/tb(2018-12) Dooley, Kelly E; Kaplan, Richard; Mwelase, Noluthando; Grinsztejn, Beatriz; Ticona, Eduardo; Lacerda, Marcus; Sued, Omar; Belonosova, Elena; Ait‐Khaled, Mounir; Angelis, Kostas; Brown, Dannae; Singh, Rajendra; Talarico, Christine; Tenorio, Allan; Keegan, Michael; Aboud, Michael; Zajdenverg, RobertoIntrodução: O tratamento concomitante da tuberculose e do HIV é desafiador devido às interações medicamentosas, à sobreposição de toxicidades e à síndrome de reconstituição imune (IRIS/SIRI). Objetivo: A eficácia e a segurança de dolutegravir (DTG) foram avaliadas nos adultos coinfectados com HIV e tuberculose. Metodologia: Inspiring é um estudo fase 3 b, aberto, não comparativo, com controle ativo, randomizado, em adultos que vivem com HIV‐1, virgens de tratamento (CD4+ > ou = 50 cels/mm3) com TB responsiva ao tratamento. Os participantes em tratamento para TB baseado em rifampicina até oito semanas foram randomizados (3:2) para receber DTG (50 mg duas vezes ao dia até duas semanas após término do tratamento da TB, seguido por 50 mg uma vez ao dia) ou EFV (600 mg uma vez ao dia) com dois ITRNs por 52 semanas. O desfecho primário foi a proporção de voluntários em uso de DTG com HIV‐1 < 50 c/mL (respondedores). Resultado: Os participantes foram randomizados para DTG (n = 69) ou EFV (n = 44). A proporção de respondedores na semana 48 (ITT‐E) foi 52/69 (75%) para DTG e 36/44 (82%) para EFV. Ausência de resposta ao DTG foi decorrente primordialmente por interrupções não relacionadas ao tratamento: 11 voluntários (16%) com DTG e três (7%) com EFV descontinuaram por razões não relacionadas ao tratamento, embora suprimidos (principalmente por perda de seguimento). Houve duas falhas virológicas definidas pelo protocolo (PDVF), mas sem emergência de mutações de resistência ao tratamento (RAMs) no braço de DTG e uma PDVF com EFV, com RAMs para ITRN e ITRNN. A mediana de aumento da contagem de CD4+ na semana 48 foi de 220 cels/mm3 com DTG e 190 cels/mm3 com EFV. Dois voluntários em uso de EFV interromperam o tratamento por eventos adversos. As taxas de IRIS associada à TB foram baixas (DTG, n = 4 [6%]; EFV, n = 4 [9%]). Nenhum participante interrompeu o tratamento por causa de IRIS nem por eventos hepáticos. O sucesso do tratamento da tuberculose foi de 61/69 (88%) e 39/44 (89%) com DTG e EFV, respectivamente. A mediana de concentração mínima de DTG durante o uso de dolutegravir duas vezes ao dia com rifampicina foi semelhante à de dolutegravir uma vez ao dia sem rifampicina. Discussão/conclusão: Esses resultados revelam que dolutegravir (DTG) é eficaz e bem tolerado em adultos coinfectados por TB e HIV que recebem tratamento para tuberculose com rifampicina.Item Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection(2018-04-27) Vecchione, María Belén; Eiras, Javier; Suarez, Guadalupe Verónica; Angerami, Matías Tomás; Marquez, Cecilia; Sued, Omar; Ben, Graciela; Pérez, Héctor Miguel; Gonzalez, Diego; Maidana, Patricia; Mesch, Viviana; Quiroga, María Florencia; Bruttomesso, Andrea ClaudiaAn estimated one third of the world’s population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.Item Infección por HPV de alto riesgo y lesiones intraepiteliales anales en hombres HIV positivos que tienen sexo con hombres(2018-06-01) Valeria, Fink; Svidler López, Laura; González, Fernanda; Tejo, Mariana; Presencia, Gisela; Sidra, Gabriela; Galperín, María Victoria; Pastore, Rita Ofelia L; Figurelli, Silvina; Mammana, Lilia; Cesar, Carina; Sued, Omar; Bouzas, Maria Belen; Cahn, PedroIntroducción: El cáncer anal, asociado a la infección con virus de papiloma humano de alto riesgo (HPV-AR), es muy frecuente en hombres que tienen sexo con hombres (HSH) HIV+. Objetivo: Evaluar frecuencia de infección por HPV-AR, genotipos y lesiones asociadas, y factores asociados. Materiales y métodos: Estudio en HSH HIV+ (septiembre 2012-marzo 2014, Hospital Fernández). Se recogió información demográfica, de HIV, HPV y prácticas sexuales. Se realizó citología anal, detección de HPV-AR (HC2 High- Risk HPV DNA, Digene®) y genotipificación en las muestras HPV-AR+ (Inno Lipa®, Fujirebio). Los pacientes firmaron consentimiento informado. Se indicó tratamiento según resultados. Resultados: Completaron el estudio 57 pacientes. Mediana de edad: 40 años (rango intercuartil [RIC]: 29-45); de CD4: 444 cels/mm3 (RIC: 345-568); 77% recibían tratamiento antirretroviral, 68% con carga viral no detectable. Citologías: negativas (24%); lesión intraepitelial de bajo grado (54%); lesión intraepitelial de alto grado (20%); ASCUS (2%). El 80% fue HPV-AR+. Los pacientes con diagnóstico de HPV-AR (p=0,006) y de lesión intraepitelial tuvieron CD4 <500 cels/ mm3 con más frecuencia (p=0,030). Los pacientes con HPV-AR tuvieron mayor frecuencia de carga viral detectable (p=0,020, prueba de Fisher). El porcentaje de pacientes con uso consistente de preservativo fue mayor entre los pacientes sin lesión citológica (p=0,026). Genotipos de alto riesgo más frecuentes: HPV-16 (51%), HPV-31 (44%) y HPV-51 (40%); de bajo riesgo: HPV-6 (47%) y HPV-44 (35%). Conclusiones: Se encontró elevada frecuencia de lesión citológica (76%) y de HPV-AR (80%). Es necesario establecer estrategias de prevención en esta población incluyendo tamizaje, vacunación y promoción de sexo seguro.Item PD-1 Expression in HIV-Specific CD8+ T cells Before Antiretroviral Therapy Is Associated With HIV Persistence(2019-01) Ghiglione, Yanina; Trifone, César; Salido, Jimena; Rhodes, Ajantha; Ruiz, Maria; Polo, María Laura; Salomon, Horacio ; Laufer, Natalia; Sued, Omar; Lewin, Sharon; Turk, GabrielaBackground: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8+ T-cell function and phenotype before therapy and HIV persistence on ART. Methods: Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics. Results: Elevated immune activation, dominance of monofunctional CD8+ T cells, and skewed distribution of memory profile were observed before ART. After ART initiation, HIV DNA and US-RNA levels rapidly diminished, reaching a plateau by 30 weeks after ART. The proportion of baseline HIV-specific effector memory and terminal effector CD8+ T cells directly correlated with HIV DNA levels at 1 year after ART. A strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1High CD8+ T cells measured before ART and HIV DNA at 1 year after ART. Conclusions: A higher proportion of terminally differentiated CD8+ T cells and increased PD1 expression were associated with HIV persistence on ART after treatment of primary infection. Thus, the quality of the early CD8+ T-cell immune response may serve as a predictor of HIV persistence on ART.Item Survival after cancer diagnosis in a cohort of HIV-positive individuals in Latin America(2018-05-08) Fink, Valeria; Jenkins, Cathy A; Castilho, Jessica L; Person, Anna K; Shepherd, Bryan E; Grinsztejn, Beatriz; Netto, Juliana; Crabtree-Ramirez, Brenda; Cortes, Claudia; Padgett, Denis; Jayathilake, Karu; McGowan, Catherine; Cahn, PedroBackground This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Methods Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. Results Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32–47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p = 0.02), age (aHR = 1.02 per year, p = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p = 0.01). Conclusion ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.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, PedroBackground: 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.Item Functionality of CD8+ T-cells in subjects under cART: implications on cure strategies(2018-08) Salido, J; Ruiz, Maria; Trifone, C; Figueroa, MI; Caruso, MP; Gherardi, MM; Sued, Omar; Horacio, S; Natalia, L; Ghiglione, Y; Turk, GabrielaBackground: Reaching HIV cure will largely depend on the capacity of HIV-specific memory CD8+ T-cells (CD8TC) to eliminate the viral reservoir. However, CD8TC response is limited in subjects on cART. Here, we aimed to investigate the phenotype and function of in vitro expanded CD8TCs in HIV+ subjects and the impact of ART initiation timing on these parameters. Methods & Materials: PBMCs from 28 HIV+ subjects on cART for 1 year were obtained. Twelve initiated treatment during chronic infection (Delayed Treatment, DT) and 16 within four months post-infection (Early Treatment, ET). PBMCs were stimulated with peptides spanning Nef and Gag plus IL-2 during 14 days. ELISPOT (pre and post-expansion) and Flow Cytometry (FC, post-expansion) were performed to assess expanded CD8TC function (CD107a/b, IFN-g, IL-2, MIP-1b and TNF-a) and phenotype (CD45RO, CCR7, CD95 and PD1). Data was analyzed using non-parametric statistics. Results: Magnitude of ELISPOT responses increased after expansion by 103 times (p < 0.002), in both groups, being this effect more pronounced in CD8TCs, compared to CD4TCs (p < 0.0001), as confirmed by FC. Cells showed higher avidity after stimulation (evidenced by greater spot sizes, p < 0.002). DT subjects displayed a broader response to HIV than ET, after expansion. ET group had a significantly higher proportion of monofunctional degranulating CD8TCs (CD107a/b+), when challenged against Gag peptides (p = 0.037) compared to DT. Contrary, DT group showed higher polyfunctionality (p = 0.009). In both groups, CD4TC responses were of lesser magnitude compared to CD8TCs and predominantly monofunctional. Bulk and HIV-specific CD8TC phenotype varied significantly between groups: ET subjects showed a preservation of stem and central memory cells while DT showed a fully-differentiated profile (p < 0.005). When analyzing memory distribution within PD1+CD8+ cells, terminal effector were the most frequent subpopulation in DT and effector memory cells in ET individuals; evidencing a differential cell exhaustion profile in both groups. Conclusion: We demonstrated that HIV-specific CD8TCs could be selectively stimulated and expanded in subjects under ART. We also showed that ART initiation timing has an impact on phenotype and function of CD8TCs, reflecting consequences of longer antigen persistence on immune function. Overall, results presented in this work have important implications for the development of cure strategies aim at boosting CD8TC responses.Item Trends in proportion of older HIV-infected people in care in Latin America and the Caribbean: a growing challenge(2018-05-30) Caro-Vega, Y; Belaunzarán-Zamudio, PF; Crabtree-Ramírez, B; Shepherd, BE; Mejia, F; Giganti, MJ; Patterson, Patricia; Grinsztejn, B; Wolff, M; Pape, JW; Padgett, D; Castilho, JL; Pape, JW; Padgett, D; Castilho, JL; McGowan, C; Sierra-Madero, JGWe aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.Item Early Retention in Care Neither Mediates Nor Modifies the Effect of Sex and Sexual Mode of HIV Acquisition on HIV Survival in the Americas(https://doi.org/10.1089/apc.2018.0028, 2018-08-01) Coelho, Lara; Rebeiro, Peter F; Castilho, Jessica L; Caro-Vega, Yanink; Mejia, Fernando A; Cesar, Carina; Cortes, Claudia; Padgett, Denis; McGowan, Catherine C; Veloso, Valdiléa G; Sterling, Timothy R; Grinsztejn, Beatriz; Shepherd, Bryan E; Luz, Paula M; for the CCASAnetEarly retention in care, sex, and sexual mode of HIV acquisition has been associated with mortality risk among persons living with HIV (PLWH). We assessed whether early retention in care mediates or modifies the association between mortality and sex and sexual mode of HIV acquisition among PLWH on antiretroviral therapy (ART) in the Americas. ART-naïve, adult PLWH (≥18 years) enrolling at Caribbean, Central and South America network for HIV epidemiology (CCASAnet) and Vanderbilt Comprehensive Care Clinic sites 2000–2015, starting ART, and with ≥1 visit after ART-start were included. Early retention in care was defined as ≥2 HIV care visits/labs ≥90 days apart in the first year of ART. Cox models assessed the association between early retention in care, sex, and sexual mode of HIV acquisition [i.e., women, heterosexual men and men who have sex with men (MSM)], and mortality. Associations were estimated separately by site and pooled. Among 11,721 included PLWH (median follow-up, 4.3 years; interquartile range, 2.0–7.6), 647 died (rate = 10.9/1000 person-years) and 1985 were lost to follow-up (rate = 33.6/1000 person-years). After adjustment for confounders, early retention in care was associated with lower mortality during subsequent years (pooled hazard ratio = 0.47; 95% confidence interval = 0.39–0.57). MSM had lower and heterosexual men had comparable mortality risk to women; risks were similar when adjusting for early retention in care. Additionally, no evidence of an interaction between early retention in care and sex and sexual mode of HIV acquisition on mortality was observed (p > 0.05). Early retention in care substantially reduced mortality but does not mediate or modify the association between sex and sexual mode of HIV acquisition and mortality in our population.