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Hace ya 30 años, Fundación Huésped comenzó a publicar su revista Actualizaciones en SIDA con el objeto de difundir los diferentes aspectos médicos y sociales relacionados con la desafiante problemática del VIH/ sida. Veinte años después, en 2013, considerando el prestigio alcanzado por Actualizaciones en SIDA y la necesidad de crecimiento y expansión de su canal de difusión científica, la Sociedad Argentina de Infectología (SADI) se incorporó como institución coeditora. A partir de ese momento, se ampliaron los contenidos de la revista hacia todos los aspectos vinculados con las enfermedades infecciosas más allá del VIH/sida, por lo que se decidió cambiar su denominación por la de Actualizaciones en Sida e Infectología (ASEI). Numerosos colegas han hecho su aporte para que ASEI sea hoy en día la principal publicación científica en el campo de la infectología argentina, y una de las más importantes en el mundo de habla hispana. ¡Pero queremos ir por más! Quienes hacemos ASEI queremos cumplir con el sueño de tener una revista sobre infectología indexada en el máximo nivel. Y tras ese objetivo estamos trabajando arduamente. En la actualidad, ASEI se se encuentra incluida en las siguientes bases de datos: LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), http://lilacs.bvsalud.org/es/, una de las bases de datos de literatura científica en Acceso Abierto de la Red de la Biblioteca Virtual en Salud de BIREME, el Centro Latinoamericano y del Caribe de Información en Ciencias de la Salud dependiente de la Organización Panamericana de la Salud (OPS) y de la Organización Mundial de la Salud (OMS). En LILACS participan 26 países de la región y hay más de 603.000 registros bibliográficos de artículos en español, portugués e inglés publicados a texto completo en cerca de 900 revistas sobre ciencias de la salud. BINACIS - Bibliografía Nacional en Ciencias de la Salud. Reúne el material de los centros cooperantes de la Red Nacional de Información en Ciencias de la Salud (RENICS). Desde febrero de 2018, BINACIS forma parte del Índice Regional de BIREME, que contiene más de 144 mil registros. Latindex – Sistema Regional de Información en Línea para Revistas Científicas de América Latina, el Caribe, España y Portugal (México). Latindex es un sistema de información sobre las revistas de investigación científica, técnico-profesionales y de divulgación científica y cultural que se editan en los países de América Latina, el Caribe, España y Portugal. Actualmente, ASEI forma parte del Directorio Latindex, en el que se ofrecen datos bibliográficos y de contacto de todas las revistas registradas, tanto de publicación impresa como electrónica. Asimismo, próximamente se realizará la postulación para que la revista integre el catálogo de publicaciones de esta base de datos de información científica, para lo cual venimos realizando un proceso de modificaciones en la política editorial acorde a los requisitos establecidos por Latindex. El ingreso al este último catálogo habilitará a ASEI a presentar su postulación para ingresar al Núcleo Básico de Revistas Científicas Argentinas, un proyecto del Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (Conicet) que establece un conjunto de publicaciones científicas y tecnológicas nacionales en los distintos campos del conocimiento que son sometidas a una evaluación exhaustiva con criterios únicos definidos de calidad y trascendencia. Actualmente, esta base está conformada por 359 revistas, de las cuales 50 son de ciencias biológicas y de la salud. Todos estos pasos son necesarios para intentar alcanzar el acceso a bases de datos científicas internacionales de mayor relevancia, como es el caso de MEDLINE, a fin de incrementar aun más la difusión y el impacto de nuestra revista. Como parte de este proceso de reconversión, ASEI ha encarado una renovación del equipo de asesores editoriales, con la integración de un Consejo Asesor más reducido y de más activa participación y responsabilidad editorial, con miembros que serán renovados inicialmente cada dos años. Por tal motivo, queremos agradecer a tantos profesionales que nos han acompañado desde hace años como miembros de nuestros Comités Científico y Asesor, prestigiando sin dudas a la revista. Por supuesto, todos estos cambios se conjugan con la permanente invitación a nuestros lectores a que continúen contribuyendo con estos objetivos mediante el envío de artículos para ser evaluados para publicación en la revista. De esa manera podremos cumplir con el anhelo de tener una revista argentina de infectología indexada en las principales bases de datos. ¡Sabemos que es posible, solo tenemos que trabajar para ello!

Background Evidence among key populations supports acceptability of HIV self-testing (HIVST) due to its privacy and convenience. However, insufficient research has been done among transgender women (TGW), especially in Latin America. Consequently, the aim of this study was to explore the acceptability, perceptions and recommendations for HIVST implementation among TGW in Buenos Aires. Methods A focus group was conducted in July 2019. Particpants were invited to touch and learn about a displayed HIVST kit. The following main topics were explored: acceptability, reasons for seeking self-testing, preferences for training, distribution, periodicity and recommendations for HIVST implementation. Results The sample consisted of 12 TGWs; mean age of 26 years (IQR = 22–28); 66% had history of sex-work. The main motivations for seeking HIVST were convenience, privacy, and usage to reduce stigma and discrimination by health-care providers. Recommendations for HIVST were: distribution from primary health centers and trans-sensitive centers; affordable price; assistance by peer health promoters; and the provision of clear written and video instructions. Conclusions Tailored implementation of HIVST can increase HIV testing rates, early detection, and linkage to HIV-care in this high-prevalence group. This study provided community-driven suggestions to inform and adapt an HIVST feasibility pilot study and future implementation in Argentina.

Evidence indicates that the microbiome plays a significant role in HIV immunopathogenesis as well as in HIV-associated complications. In Argentina, men who have sex with men (MSM) and transgender women (TGW) are at the highest risk for infection with HIV and AIDS-related viruses. This study aimed to characterize the oral and anal microbiome of MSM and TGW with and without HIV. One hundred and thirty oral and anal DNA-derived samples were obtained from 78 participants and subjected to shotgun metagenomics sequencing for further microbiome analysis. Results: A significantly lower alpha diversity and higher beta diversity were found in the anal samples compared with oral samples. Significant differences in the microbiome composition were found among subjects associated with HIV infection, gender, sex behavior, CD4+ T cell counts, antiretroviral therapy (ART) and the presence of HPV-associated precancerous anal lesions. For viruses, results confirm the occurrence of oncogenic viromes in this high HIV-risk population. The HIV-associated oral microbiome was characterized by the enrichment of several bacteria related to periodontal disease pathogenesis. Conversely, predominantly anal bacteria showed a significant decrease in HIV-infected subjects (Coprococcus comes, Finegoldia magna, Blautia obeum, Catenibacterium mitsuokai). TGW showed enrichment in species related to sexual transmission, which concurs that most recruited TGW are or have been sex workers. Prevotella bivia and Fusobacterium gonidiaformans were positively associated with the presence of anal precancerous lesions among HIV-infected subjects. The enrichment of Holdemanella biformis and C. comes were associated with detectable viral load and ART untreated patients. Metabolic pathways were distinctively affected according to whether the predominant factors were associated with sexual behavior or HIV pathogenesis. Gene family analysis identified bacterial gene signatures that may potentially be prognostic and/or predictive biomarkers of HIV/AIDS-associated malignancies. Conclusions: We have identified distinctive microbial features at two easily accessible sites related to HIV immunopathogenesis. These could also be implemented as potential biomarkers to predict the risk of precancerous anal lesions or as therapeutic targets.

To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.Design:Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).Methods:Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.Results:At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA, This study was funded by ViiV Healthcare

La terapia antirretroviral de alta eficiencia (TAAE) nació como la combinación de tres drogas en 1996, y desde entonces es el estándar de cuidado en todas las guías de tratamiento, debido a su extraordinario impacto en la reducción de la morbimortalidad asociada al VIH/sida. Las primeras combinaciones eran complejas de tomar y tolerar para los pacientes. Las primeras generaciones de personas viviendo con VIH y de profesionales tratantes tuvieron que lidiar con esquemas de hasta 24 tabletas diarias, en tres tomas por día, con severos efectos adversos asociados tanto a los inhibidores nucleósidos de la transcriptasa reversa (INTR) de primera generación (zidovudina, stavudina y didanosina) como a los inhibidores de la proteasa (saquinavir, ritonavir, nelfinavir e indinavir). En la actualidad, tenemos regímenes de terapia triple más eficaces, mejor tolerados y más simples, basados en una o a lo sumo dos tabletas al día para su indicación en el inicio de tratamiento, así como en casos de personas con supresión virológica recibiendo regímenes más complejos. Los regímenes recomendados en las guías locales e internacionales han mostrado en los estudios que fundamentaron su aprobación, niveles de supresión virológica superiores al 90%. Resulta difícil imaginar que nuevas drogas puedan exceder esa marca. Las toxicidades remanentes en los esquemas actuales (aunque marcadamente menos frecuentes y severas que las descriptas en el párrafo anterior) presentan un obstáculo para la adhe- rencia al tratamiento en ciertos casos (1). A la fecha, el TAAE es de por vida. Y como resultado del mismo la expectativa de vida de una persona viviendo con VIH (PVCH) es similar a la de una persona VIH negativa, siempre que logre mantener suprimida la replicación viral, lo que implica la coexistencia de la infección viral crónica con las comorbilidades asociadas a la edad avanzada y la polifarmacia consecuente, con su potencial riesgo de interacciones medicamentosas. Por lo expuesto, la investigación de nuevas estrategias se ha orientado en los últimos años a la búsqueda de opciones más simples, tendiendo a la reducción de la carga de drogas (terapia doble) o bien regímenes de administración intermitente, por vía inyectable IM o SC, implantes o medicación oral de liberación prolongada. En esa línea, diversos estudios exploraron la simplificación del tratamiento ARV utilizando dos drogas en vez de tres. Los estudios iniciales, basados en reducir los esquemas de dos INTR más un IP o un INNTR quitando la tercera droga, fallaron en su intento de demostrar no inferioridad. Otros intentos, asociando dos drogas (IP + INNTR; IP + maraviroc, entre otros), tampoco resultaron exitosos. Más aun, la asociación de dos excelentes fármacos como raltegravir y darunavir/ritonavir (2) no pudo demostrar no inferioridad en el estrato de pacientes con más de 100.000 copias de carga viral basal o CD4 inferiores a 200 células/mm3. Por lo observado hasta ahora, parece ser imprescindible incluir un inhibidor de la transcriptasa reversa para obtener un esquema exitoso de terapia doble. La observación de un alto porcentaje de supresión viral con IP en monoterapia (si bien insuficiente para demostrar no inferioridad) nos motivó a considerar como pregunta de investigación qué sucedería si se asociara un IP con lamivudina (3TC) para inicio de tratamiento. Generamos esta hipótesis basados en la excelente tolera- bilidad del 3TC, su comodidad posológica, su bajo costo y su particular actividad residual, aun en presencia de la mutación M184V/I por su efecto sobre la capacidad replicativa del VIH (3). Así nació el estudio GARDEL (4), primer estudio multicéntrico, randomizado, con poder estadístico para poder demostrar la no inferioridad del esquema de lopinavir/ritonavir más 3TC comparado con el mismo IP más dos INTR en pacientes que inician tratamiento. La no inferioridad fue demostrada a las 48 semanas y confirmada a las 96 semanas, incluyendo el estrato de pacientes con carga viral basal mayor a 100.000 copias/mL. Posteriormente, el estudio ANDES confirmó esos hallazgos utilizando la coformulación de darunavir/ritonavir 800/100 mg asociada al 3TC. En paralelo, observando la potencia, comodidad posológica y tolerabilidad de los inhibidores de la integrasa (INSTI) de segunda generación (dolutegravir y bictegravir), exploramos la terapia doble con dolutegravir y 3TC en el estudio PADDLE, un piloto con 20 pacientes que mostró 90% de supresión viral a 48 y 96 semanas en el análisis por intención de tratamiento y 95% en el análisis por protocolo. Este estudio fue seguido por el ACTG 5353, que incorporó 120 pacientes, con similares resultados. Ambos estudios fundamentaron la realización de los estudios GEMINI (5), fase 3, randomizados, muticéntricos, doble ciego que incluyeron más de 1400 participantes, confirmando la no inferioridad de la asociación dolutegravir+3TC respecto del esquema dolutegravir +Tenofovir/FTC. De esta manera se estableció una nueva alternativa para inicio del TARV en diferentes guías de tratamiento (6), incluyendo las de la Sociedad Argentina de Infectología (SADI) y del Ministerio de Salud de la Nación. Ya en 2017 la Administración de Alimentos y Medicamentos de los Estados Unidos (FDA) había aprobado la primera combinación de terapia doble para simplificación del tratamiento en pacientes con carga viral indetectable, consistente en dolutegravir y rilpivirina, régimen no disponible en la Argentina. Algunas guías limitan la indicación de Dolutegravir+3TC a pacientes con carga viral inferior a 500.000 copias/mL y/o recuentos de CD4 menores a 200 células/mL, aunque esta última limitación no está establecida por la FDA ni por la European Medicines Agency (EMA). Los estudios TANGO y SALSA demostraron la no inferioridad de DTG/3TC en simplificación para pacientes con supresión virológica respecto a la terapia triple basada en TAF (TANGO) o en cualquier régimen de triterapia (SALSA). Esta opción de terapia doble también fue incorpora- da en las guías arriba mencionadas. Nuevos compuestos como el lenacapavir (inhibidor de la capside viral) y el islatravir (inhibidor de la translocación) están siendo ensayados en estrategias de terapia dual, aunque islatravir tiene sus ensayos suspendidos por la aparición inesperada de un impacto negativo sobre el recuento linfocitario y de células CD4. ¿Implica esto el reemplazo de la triterapia por terapia doble en todos los casos? La respuesta es no. La terapia doble no ha sido ensayada en niños, mujeres embarazadas ni en casos de TBC tratada con rifampicina, está contraindicada en caso de infección activa por hepatitis B, así como en casos de fallo previo al tratamiento. Pero sin duda representa una nueva alternativa para inicio y simplificación de tratamiento. Mientras se persiste en la búsqueda de la cura, el desarrollo de nuevas estrategias pasa por regímenes con menos carga de drogas, ya sea por reducción del número de fármacos o por estrategias de liberación prolongada que eviten la toma diaria del TARV. Hacia allí vamos.

Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.

BackgroundDual therapy has emerged as a novel concept for HIV treatment. The ARTE study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.MethodsRandomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (ResultsOut of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and, 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/μL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.ConclusionATV/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.This study is registered with ClinicalTrials.gov, Number: NCT01829802

Transgender women (TGW) experience high prevalence of depression worldwide.This study analyzed the prevalence and correlates of depressive symptoms among 61 HIV + TGW (age: M = 29.87 years, SD = 6....

Purpose: Stigma toward transgender women (TGW) increases psychosocial vulnerability, leading to poor mental health and affecting access and retention in HIV care. Trans-sensitive health care (TSHC) has the potential to mitigate this adverse impact. This study aimed to describe baseline characteristics in gender identity stigma (GIS), mental health, and substance use among TGW living with HIV initiating antiretroviral treatment and to analyze changes after 6 months in HIV care in a TSHC clinic in Argentina. Methods: Sixty-one TGW living with HIV responded to the following questionnaires at baseline and after 6 months in TSHC: sociodemographic, experiences of GIS (in health care, police, etc.), Center for Epidemiologic Studies Depression Scale (CES-D) (depression), State Trait Anxiety Inventory (STAI) (anxiety), Drug Abuse Screening Test (DAST-10) (drug use), Alcohol Use Disorders Identification Test (AUDIT) (alcohol use), 8-item Personal Wellbeing Index—Adults (PWI-A) (quality of life [QOL]), Personality Inventory for DSM-5—Brief Form (PID-5-BF) (maladaptive personality traits), and Duke Index (social support). Analyses included Pearson correlations to analyze associations between variables; and paired sample t-tests, to explore changes between baseline and 6 months. Results: A significant proportion experienced episodes of GIS the last year in any context. At baseline, 50.8% showed significant depressive symptoms and 65.6% reported any drug use in the last year. At 6 months, participants experienced a significant reduction of GIS, both enacted and internalized, anxiety, drug, and alcohol use, and improvement in QOL. The remaining mental health indicators were not significantly modified. Conclusion: A TSHC service may have a gender-affirmative impact on TGW initiating HIV care that contributes to reduce GIS and substance use and improve mental health. This highlights the importance that HIV care programs for TGW comply with trans-sensitive essential components to enhance retention.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96. The incidence of PDVF was as expected in this difficult-to-treat patient population and, among RC participants, was comparable regardless of the presence of predefined gp120 amino acid substitutions that potentially influence phenotypic susceptibility to temsavir (S375H/I/M/N/T, M426L, M434I, M475I) or baseline temsavir 50% inhibitory concentration fold change (IC

Background To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)–infected patients. Methods RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4+ cell count, and antiviral resistance were evaluated. Results Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3–4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA + cell count increased over time until week 192 and remained constant thereafter. Conclusions RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.

Background: Fostemsavir, a prodrug of the first-in-class attachment inhibitor, temsavir, is indicated for heavily treatment-experienced individuals with multidrug-resistant HIV-1. We previously reported superior efficacy of fostemsavir versus placebo in the randomised cohort of the BRIGHTE study after 8-day functional monotherapy (primary endpoint); here we report planned interim analyses through week 96. Methods: BRIGHTE (NCT02362503) is an ongoing multicentre, two-cohort, phase 3 trial, done at 108 centres in 22 countries. We enrolled heavily treatment-experienced adults (≥18 years) failing antiretroviral therapy (HIV-1 RNA ≥400 copies per mL) into two cohorts: the randomised cohort, in which patients with one or two fully active antiretrovirals remaining received oral fostemsavir (600 mg twice a day) or placebo in combination with their failing regimen for 8 days, followed by fostemsavir plus optimised background therapy; or the non-randomised cohort, in which patients with no remaining antiretroviral options received oral fostemsavir (600 mg twice a day) plus optimised background therapy from day 1. Endpoints for the week 96 interim analyses included the proportions of participants with plasma HIV-1 RNA of less than 40 copies per mL, changes from baseline in CD4 cell counts, and the frequency of adverse events, adverse events leading to discontinuation, and deaths. The intention-to-treat exposed population and the safety population both included all participants who received at least one dose of study treatment. The response rates (proportion of participants with HIV-1 RNA

Cumulative burden of multiple mental health conditions may worsen physical health outcomes in vulnerable populations. Accordingly, identifying cumulative burdens of mental health conditions that may affect HIV treatment and care can guide public health strategies to reduce their impact on HIV-related health outcomes. This study examined the relationship between the cumulative burden of mental health conditions and factors associated with engagement in HIV care in Argentina. Data for this study was obtained at baseline from Conexiones y Opciones Positivas en la Argentina 2 (COPA2). Participants (N = 360) were cisgender patients living with HIV who were lost to care, recruited from seven clinics serving people living with HIV in four Argentine urban centers. Cumulative burden of mental health conditions (i.e., depressive symptoms, problematic substance use, unhealthy alcohol use, and psychotic symptoms) was assessed. Every one-point increase in the number of mental health conditions present was associated with a decrement in patient-provider communication (b = − 0.22, p

BackgroundAlthough antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy.MethodsAn open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20

International audience; Background: Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor.Methods: In this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options. In the first cohort, we assigned (in a 3:1 ratio) patients who had the option of using at least one fully active, approved antiretroviral drug in at least one but no more than two antiretroviral classes to add either fostemsavir (at a dose of 600 mg twice daily) or placebo to their failing regimen for 8 days, followed by open-label fostemsavir plus optimized background therapy (randomized cohort). In the second cohort, patients who had no remaining antiretroviral options were started on open-label fostemsavir plus optimized background therapy on day 1 (nonrandomized cohort). The primary end point was the mean change in the HIV-1 RNA level from day 1 through day 8 in the randomized cohort.Results: A total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in the HIV-1 RNA level was 0.79 log10 copies per milliliter in the fostemsavir group and 0.17 log10 copies in the placebo group (P

Background Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. Methods In this phase ...

Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor that has shown non-inferior efficacy to ritonavir-boosted darunavir, with a superior lipid profile, in adults with HIV who were treatment naive at week 48 in the phase 3 DRIVE-FORWARD trial. Here we present the 96-week data for the study.This randomised, controlled, double-blind, multicentre, non-inferiority, phase 3 study was undertaken at 125 clinical centres in 15 countries. Eligible participants were adults (aged ≥18 years) infected with HIV-1 who were naive to antiretroviral therapy, with a plasma HIV-1 RNA concentration of 1000 copies per mL or higher at screening, and no known resistance to any of the study drugs. Participants were randomly assigned (1:1) using an interactive voice and web response system, stratified by baseline HIV-1 RNA concentration and background nucleoside reverse transcriptase inhibitor therapy, to doravirine (100 mg per day) or ritonavir-boosted darunavir (100 mg ritonavir and 800 mg darunavir per day), both with investigator-selected nucleoside reverse transcriptase inhibitors: emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. Participants and investigators were masked to treatment assignment until week 96. The primary efficacy endpoint was the proportion of participants who had a plasma HIV-1 RNA concentration of less than 50 copies per mL at week 48, which has been reported previously. Here we report the key secondary efficacy endpoint of the proportion of participants who achieved this concentration by week 96, assessed in all participants who received at least one dose of any study drug, regardless of whether it was their randomly assigned treatment. We used a US Food and Drug Administration snapshot approach and a margin of 10 percentage points to define the non-inferiority of doravirine to ritonavir-boosted darunavir at 96 weeks. Key safety endpoints were change in fasting serum lipid concentrations, the incidence of adverse events, and time to discontinuation due to an adverse event, assessed in all participants who received at least one dose of any study medication. This study is registered with ClinicalTrials.gov, NCT02275780, and is closed to accrual.Between Dec 1, 2014, and Oct 20, 2015, 1027 individuals were screened, of whom 769 participants were randomly assigned to doravirine (n=385) or ritonavir-boosted darunavir (n=384), and 383 in both groups were given at least one dose of their allocated treatment. Most participants were male (645 [84%] of 766) and white (560 [73%]), with a mean age of 35·2 years (SD 10·6). 292 participants in the doravirine group and 273 in the darunavir group completed 96 weeks of treatment. At week 96, a higher proportion of the doravirine group (277 [73%] of 383) achieved an HIV-1 RNA concentration of less than 50 copies per mL than did of the darunavir group (248 [66%] of 383; difference 7·1%, 95% CI 0·5-13·7). Responses were similar regardless of baseline characteristics. Treatment-emergent resistance to any study drug occurred in two (1%) of 383 participants in the doravirine group and one (1%) of 383 in the ritonavir-boosted darunavir group. Significant differences were seen between treatment groups in mean changes from baseline in LDL cholesterol (-14·6 mg/dL, 95% CI -18·2 to -11·0) and non-HDL cholesterol (-18·4 mg/dL, -22·5 to -14·3). Frequencies of adverse events were similar between groups. No significant treatment difference (log-rank nominal p=0·063) through week 96 was observed in time to discontinuation due to an adverse event. The most common adverse events (week 0-96) were diarrhoea (65 [17%] in the doravirine group vs 91 [24%] in the ritonavir-boosted darunavir group), nausea (45 [12%] vs 52 [14%]), headache (57 [15%] vs 46 [12%]), and upper respiratory tract infection (51 [13%] vs 30 [8%]). Two participants, one in each group, died during treatment; neither death was considered to be related to study medication.These results through 96 weeks support the efficacy and safety results reported previously for doravirine at 48 weeks, supporting the use of doravirine for the long-term treatment of adults with previously untreated HIV-1 infection.Merck.

Entry inhibitors are a relatively new class of antiretroviral therapy and are typically indicated in heavily treatment experienced individuals living with HIV. Despite this, there is no formal definition of 'heavily treatment experienced'. Interpretation of this term generally includes acknowledgement of multidrug resistance and reflects the fact that patients in need of further treatment options may have experienced multiple lines of therapy. However, it fails to recognize treatment limiting factors including contraindications, age-associated comorbidities, and difficulty adhering to regimens.This manuscript follows a roundtable discussion and aims to identify the unmet needs of those living with HIV who are in need of further treatment options, to broaden the definition of heavily treatment experienced and to clarify the use of newer agents, with an emphasis on the potential role of entry inhibitors, in this population.Within the entry inhibitor class, mechanisms of action differ between agents; resistance to one subclass does not confer resistance to others. Combinations of entry inhibitors should be considered in the same regimen, and if lack of response is seen to one entry inhibitor another can be tried. When selecting an entry inhibitor, physicians should account for patient preferences and needs as well as agent-specific clinical characteristics. Absence of documented multidrug resistance should not exclude an individual from treatment with an entry inhibitor; entry inhibitors are a valuable treatment option for all individuals who are treatment limited or treatment exhausted. We should advocate for additional clinical trials that help define the role of entry inhibitors in people with exhausted/limited ART options other than drug resistance.

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 3. 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.

Objectives: The aim of this study was to describe the incidence, clinical characteristics, and risk factors of late-onset opportunistic infections (LOI) in people who live with HIV (PWLHA) within the Caribbean, Central and South America network for HIV epidemiology. Methods: We performed a retrospective cohort study including treatment-naive PWLHA enrolled at seven sites (Argentina, Brazil, Chile, Peru, Mexico, and two sites in Honduras). Follow-up began at 6 months after treatment started. Outcomes were LOI, loss to follow-up, and death. We used a Cox proportional hazards model and a competing risks model to evaluate risk factors. Results: A total of 10,583 patients were included. Median follow up was at 5.4 years. LOI occurred in 895 (8.4%) patients. Median time to opportunistic infection was 2.1 years. The most common infections were tuberculosis (39%), esophageal candidiasis (10%), and Pneumocystis jirovecii (P. jirovecii) pneumonia (10%). Death occurred in 576 (5.4%) patients, and 3021 (28.5%) patients were lost to follow-up. A protease inhibitor–based regimen (hazard ratio 1.25), AIDS-defining events during the first 6 months of antiretroviral-treatment (hazard ratio 2.12), starting antiretroviral-treatment in earlier years (hazard ratio 1.52 for 2005 vs 2010), and treatment switch (hazard ratio 1.31) were associated with a higher risk of LOI. Conclusion: LOI occurred in nearly one in 10 patients. People with risk factors could benefit from closer follow-up.

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, CDRegional clinics (Participants were an average age of 39·15 (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.National Institutes of Health.

El día en que escribo, así como el día en que ustedes lean esta nota editorial, cerca de 5000 personas adquirirán HIV en el mundo, entre ellas, 500 niñas y niños. Hoy 2600 personas morirán a causa del sida. Esta semana, 7000 mujeres de entre 15 y 24 años se habrán infectado. Cuando hace 40 años veíamos los primeros casos de lo que después sabríamos que era la infección por HIV, pensar en terminar con la epidemia parecía una utopía. En medio de una de las emergencias de salud más importantes de la historia, la incógnita era si alguna vez iba a terminar. Era una ilusión más cercana a una fantasía que a una realidad alcanzable. Todos los días veíamos contraer el HIV y morir a cada vez más personas como consecuencia del sida. A la epidemia descontrolada se sumaban el estigma y la discriminación con que se trataba a los pacientes fuera y, aún más grave, dentro del sistema de salud.En estos 40 años hemos avanzado enormemente en nuestros conocimientos desde las ciencias básicas hasta las ciencias sociales, incluyendo, de manera destacada, los avances en el tratamiento antirretroviral.Sin embargo, cuarenta años después de la descripción de los primeros casos, la enfermedad por HIV, que es prevenible y tratable, sigue siendo transmitida y constituye una importante causa de muerte, particularmente para las poblaciones más vulnerables.¿Por qué no controlamos el HIV si es prevenible y tratable? ¿Por qué no impedimos muertes evitables? ¿Qué hace falta para controlar la epidemia?La respuesta es muy simple: voluntad política, liderazgo e inversión eficiente. El mundo se puso como objetivo controlar el HIV en 2020. No se pudo. Pasó al 2030. ¿Se podrá? Cumplir esta meta se lo debemos a los 39 millones de personas que murieron a causa de la enfermedad hasta ahora, y además es un compromiso ineludible con las personas que hoy viven con el virus y con las generaciones que vienen. Sin embargo, aun cumpliendo los objetivos de ONUSIDA del 90/90/90, el 27% de las personas que viven con el virus no tendrían su carga viral indetectable, y por lo tanto estarían en riesgo de enfermar, morir y transmitir la infección. Aun si alcanzáramos el 90/90/90 sería insuficiente para los casi 10 millones que seguirían con su viremia no controlada. La expansión universal del TARV es un imperativo ético, pero también sanitario. Cada día perdido lo pagan miles de mujeres, hombres y niños con sus vidas.El diagnóstico y el tratamiento tempranos combinados con los beneficios de la terapia antirretroviral, permiten que las personas con HIV tengan una calidad de vida similar a la de que aquellas que no tienen el virus. Así, se reducen las muertes relacionadas con el sida, y a la vez disminuyen las posibilidades de nuevas infecciones a medida que las personas con HIV alcanzan niveles indetectables de virus en la sangre. Hoy quien accede a y cumple con un tratamiento exitoso ya no transmite la infección a su pareja (I=I).En nuestro país, el acceso al diagnóstico y tratamiento es gratuito por ley. La seguridad social, las prepagas y, principalmente, el Estado nacional brindan estos servicios… a los que los solicitan. Así, el sistema reproduce su carácter darwiniano, seleccionando a los más aptos. ¿Quiénes son los más aptos? Los que tienen tiempo, salud suficiente y fondos para costearse el transporte para ir a los centros de salud. Los que no dependen de cobrar el presentismo y quienes no lo perderían en caso de ir al hospital en el estrecho horario que suelen ofrecer nuestros sistemas, más adaptados a los horarios de los equipos de salud que a las necesidades de los pacientes. De esta manera, el sistema de salud reproduce y amplifica el más importante determinante de enfermedad en nuestras sociedades: la desigualdad social. Finalmente, quienes no vienen a tiempo, llegan al sistema de salud. Los traen en ambulancia, con su enfermedad avanzada.¿Cómo abordar esta situación? Descentralizando el testeo, acercando la salud a las personas en vez de esperar pasivamente que vengan. Masificando los test rápidos, promoviendo el autotest, eliminando las barreras burocráticas que dificultan el testeo, implementando el tratamiento inmediato (en lo posible el mismo día) y teniendo una política proactiva de retención en el cuidado y recuperación de las personas perdidas en su seguimiento. Implementar el tratamiento como eje central de la prevención en el marco de un conjunto que incluya otras acciones como la educación sexual, la promoción del uso de preservativos, la PrEP, la reducción de daños y el combate al estigma y la discriminación es hoy más relevante que nunca. En nuestro país se estima que más del 17% de las personas que viven con HIV desconocen su situación. Son, en teoría, alrededor de 22.000 individuos en riesgo de enfermar, transmitir y morir. Los lectores con “DNI de números bajos” recordarán una película española, llamada Solos en la madrugada, donde José Sacristán interpreta a un conductor de radio que se dirige a su audiencia después de la muerte del dictador Francisco Franco. Y les dice: “No podemos pasarnos los próximos 40 años hablando de los 40 años de dictadura”.Parece aplicable a nuestra actitud frente a la epidemia. Debemos decidir si queremos ser parte de la solución. Si no lo hacemos, seremos parte del problema. No podemos pasarnos otros 40 años hablando de los 40 años. Es hora de actuar. El desafío para todos es acortar los plazos y que el acceso al diagnóstico y al tratamiento oportuno sea universal, para controlar la epidemia de HIV/sida de una vez y para siempre. Pedro CahnDirector CientíficoFundación Huésped

Argentina has one of the highest suicide rates in Latin America and the Caribbean. Though people living with HIV are at increased risk for suicidal behavior, little research on suicide risk has been conducted among HIV-positive people in this region. This study examined risk factors for suicidal ideation among HIV-infected adults (N = 360) re-engaging in care in Argentina. Overall, 21% of participants reported suicidal ideation in the past week. In adjusted logistic regression models, younger age, increased depressive symptomatology, and drug abuse were associated with suicidal ideation (p

Introducción: Chemsex está relacionado con el uso de ciertas drogas que facilitan la excitación y el prolongar la duración de los encuentros sexuales. Objetivo: Describir el perfil de consumo de los usuarios de sustancias durante las relaciones sexuales (SRS) y su relación con variables demográficas, de estilo de vida y de salud. Métodos: Estudio descriptivo y transversal realizado a través de una encuesta autoadministrada y anónima en el marco de la plataforma Google Forms® que se transmitió en diferentes redes sociales. Objetivo: describir los aspectos demográficos y de estilo de vida de los encuestados y del subgrupo de usuarios de SRS y chemsex. Resultados: Se recibieron 2924 encuestas; 421 personas (16,9%) refirieron haber consumido al menos una vez uno o más de los siguientes: mefedrona, metanfetamina, crystal meth, GHB/GBL, cocaína, LSD, poppers, ketamina y éxtasis. Chemsex se definió como el consumo de los tres primeros y su prevalencia fue del 1,1%. El perfil de usuario de SRS y chemsex en nuestro estudio fue un hombre de entre 26 y 35 años, HSH y habitante de la Ciudad de Buenos Aires. Hubo mayor proporción de personas con VIH y diagnósticos de ITS en el último año dentro de los usuarios de SRS y chemsex. Conclusiones: Esta es la primera encuesta que trata este tema en nuestro país y en América Latina. Teniendo en cuenta la tendencia a un menor uso de los condones y a presentar más diagnósticos de ITS y VIH en la población de usuarios de SRS, consideramos de interés conocer la epidemiología en nuestra población.

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.

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 in Argentina disengaged from care. Methods: Regional clinics (n = 6) were randomized to condition, MI Intervention, Enhanced Standard of Care (ESOC), and recruited N = 360 disengaged patients disengaged from HIV care. Participants 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. 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 = ·001). There was an indirect effect of condition on ART adherence (B = 0·188, p = ·009), HIV viral load (B = -0·095, p = ·027), and self-efficacy (B = 0·063, p= ·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. Intervention participants reported greater satisfaction with patient-provider relationships (p = ·005), higher ART adherence (p = ·02), CD4+ counts NS, and lower HIV viral load (p = ·015). Retention in HIV care was higher at 12 months but not sustained. Interpretation: Physician-delivered MI enhanced patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. Implementation of sustained collaborative patient-centered MI in HIV clinical settings could strengthen patient-provider relationships and re-engage patients in their own care. Trial Registration: This study was registered at clinicaltrials.gov, NCT02846350. Funding: National Institutes of Health. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: This study was approved by the Institutional Review Board at the University of Miami Miller School of Medicine and at by each participating center.

Background: Passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of easily scaled up neutralizing antibodies against SARS-CoV-2. Methods: We conducted a double-blind, randomized, placebo-controlled trial of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 (ClinicalTrials.gov number NCT04494984). Findings: Enrolled patients were assigned to receive two doses of INM005 (n=118) or placebo (n=123). Median age was 54 years old, 65·1% were male and 61% had moderate disease at baseline. The median time from the onset of COVID-19 symptoms to the administration of the first dose of intervention was 6 days (interquartile range 5 to 8 days). At day 28 no significant difference was noted between study groups on primary endpoint (odds ratio, 1·61%, 95% confidence interval [95%CI] 0·71 to 3·63 p=0·34); however, overall variation in ordinal clinical status during the 28 days follow up period favored INM005. Improvement in at least two categories was significantly higher in INM005 at days 7, 14 and 21 of follow up. A significant difference was noted in time to improvement in at least two ordinal categories or hospital discharge: 14·2 (± 0·7) days in the INM005 group and 16·3 (± 0·7) days in the placebo group. Pre-specified subgroup analyses showed a more pronounced effect of the intervention over severe patients and with no antibody response at baseline. Overall mortality was 6·8% the INM005 group and 11·4% in the placebo group. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease. Funding: Funded by Inmunova and grants from the Ministries of Science and Production of Argentina. Trial Registration: ClinicalTrials.gov number NCT04494984 Declaration of Interests: MC, SS, VZ, LM, LS, FG received grants from Ministerio de Desarrollo Productivo “Programa soluciona. reactivacion de la economia del conocimiento” and Agencia Nacional de Promocion de la Investigacion, el Desarrollo Tecnologico y la Innovacion del Ministerio de Ciencia, Tecnologia e Innovacion. MD, JF, GV, AB, FC, MFA, LB, RT, SL, DS, MI, VS, RS, PC, MMC, LA, HLL, AC, DC declare reimbursement for conduction of clinical trial as investigator of the study. PC, OS, YK report other funds from Inmunova. EN, GL, WHB, SPLL report personal fees from Inmunova. AP, B de M, SM, Gabriel L declare no competing interests. SPLL declare personal fees from Movement Disorders Society, Laboratorio Elea and Merck pharmaceuticals. Ethics Approval Statement: The study protocol was approved by the Institutional Review Boards of all participant clinical sites as well as regional or jurisdictional Ethics Committees as applicable. The Argentinean National Administration of Medicines, Food and Medical Technology (ANMAT) also approved the study protocol.

Introducción: La distancia al hospital se ha propuesto como uno de los factores limitantes para la retención en cuidado. Métodos: Estudio de cohorte retrospectiva de pacientes HIV mayores de 18 años que iniciaron seguimiento en un centro de referencia en Buenos Aires, Argentina, entre 2011 y 2013. Se consideró retención al registro de ≥1 visita médica, laboratorio (CD4 y/o CV) y/o retiro de antiretrovirales dentro del año posterior a la primera consulta. Se utilizó Google Maps® para establecer la latitud y longitud de la dirección de los pacientes y Google Maps Distance Matrix API® para la distancia domicilio-hospital y tiempo de viaje. Resultados: De los 1020 pacientes que iniciaron seguimiento se excluyeron 15 que murieron y 158 que fueron derivados. De los restantes, 816 (96,3%) tenían registrada una dirección georreferenciable en su historia clínica. La mediana de edad durante la primera visita fue de 33 (RIC 27-41) años y 654 (77,9%) pacientes eran hombres. La mediana de distancia domicilio-hospital fue 10,3 (RIC 4,4-34,7) km y el tiempo medio de viaje fue 58,5 (RIC 35-102,5) minutos. 730 pacientes (89,5%; IC 87,1-91,5%) continuaban retenidos al año. No encontramos asociación entre el tiempo de viaje ni la distancia domicilio-hospital con la retención en cuidado en esta población. Conclusiones: En adultos HIV que se atienden en un hospital público de la CABA, el tiempo de viaje y la distancia domicilio-hospital no se asocian con la retención en cuidado dentro del año de la primera visita.

BACKGROUND In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through week 48. Here, we present long-term efficacy and safety outcomes through week 144 of the DRIVE-SHIFT trial. METHODS This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at day 1 [immediate switch group (ISG); n = 447] or week 24 [delayed switch group (DSG); n = 209]. Nine ISG participants who completed week 48 but did not enter extension-1 were excluded from week 144 efficacy analyses. RESULTS At week 144, HIV-1 RNA

El año 2020 será recordado en los futuros libros de historia como el año de la pandemia de CoVID-19, producida por el virus SARS-CoV-2. No es para menos, teniendo en cuenta que, habiendo transcurrido poco más de ocho meses desde la descripción de los primeros casos en la ciudad de Wuhan, provincia de Hubei, en China, ya se han reportado aproximadamente 30 millones de infectados, con más de 1 millón de muertes en todas las regiones del planeta. América Latina se ha convertido en los últimos meses en el epicentro de la pandemia. Seis de los doce países del mundo con más casos reportados pertenecen a esta región: Brasil, Perú, México, Colombia, Chile y Argentina. Quienes editamos esta publicación somos profesionales de la salud y, como tales, estamos profundamente comprometidos con las tareas asistenciales y de investigación derivadas de este inédito desafío epidemiológico. La pandemia ha provocado una catástrofe sanitaria, social y económica, con consecuencias aún no suficientemente medidas en el plano individual. Entre los centenares de miles de enfermos y fallecidos, los trabajadores de la salud están desproporcionadamente representados. Todos aquellos que formamos parte del equipo de salud tenemos colegas que han padecido la enfermedad en sus diferentes presentaciones, incluyendo las formas críticas y, lamentablemente, la muerte. En este difícil contexto nos fue imposible editar durante el primer cuatrimestre el número 102 de nuestra revista, que se viene publicando en forma ininterrumpida desde 1993. Por eso pedimos disculpas a nuestros lectores y junto con presentarles esta (demorada) edición número 102, nos comprometemos a regularizar la publicación de los números siguientes en los próximos meses. En nombre de la Sociedad Argentina de Infectología y Fundación Huésped les agradecemos su permanente apoyo y los invitamos a enviarnos sus trabajos para su eventual publicación. Seguimos trabajando para obtener la indexación de nuestra revista en PubMed. Contamos con ustedes.

Cumulative burden of multiple mental health conditions may worsen physical health outcomes in vulnerable populations. Accordingly, identifying cumulative burdens of mental health conditions that may affect HIV treatment and care can guide public health strategies to reduce their impact on HIV-related health outcomes. This study examined the relationship between the cumulative burden of mental health conditions and factors associated with engagement in HIV care in Argentina.Data for this study was obtained at baseline from Conexiones y Opciones Positivas en la Argentina 2 (COPA2). Participants (N = 360) were cisgender patients living with HIV who were lost to care, recruited from seven clinics serving people living with HIV in four Argentine urban centers. Cumulative burden of mental health conditions (i.e., depressive symptoms, problematic substance use, unhealthy alcohol use, and psychotic symptoms) was assessed.Every one-point increase in the number of mental health conditions present was associated with a decrement in patient-provider communication (b = - 0.22, p .001), self-efficacy (b = - 0.13, p = .012), and motivation for adherence (b = - 0.11, p = .039).This study found cumulative burden of depression, problematic substance use, unhealthy alcohol use, and psychotic symptoms to be negatively associated with factors related to engagement in HIV care. Results highlight the importance of identification and treatment of challenges to mental health, in order to ameliorate their influence on engagement in HIV care.

Since its first isolation in 1983, over 77 million people became infected with the human immunodeficiency virus (HIV), and only one case has been reported in which the virus was completely removed from the body. A recent second case was reported that remains to be confirmed. Antiretroviral therapy (ART) manages to control blood viral replication and, consequently, to restore -at least partially- the functions of the immune system, with a notable positive impact on the morbidity and mortality associated with the virus. However, given the difficulty in eliminating the virus from the body, treatment should be given for life. This long-term exposure to antiretroviral drugs implies the risk of generating intolerance, toxic effects, gaps in adherence and the potential selection of resistance mutations. Another limitation is the high cost of treating 37 million persons living with HIV, most of whom are living in resource-limited countries and relying on international aid initiatives. Having these challenges in mind, there is general agreement that new approaches for preventing and treating HIV infection are needed to control the epidemic, while vaccine development efforts continue. In this regard, new generation broadly neutralising monoclonal antibodies (bnMAbs) against the HIV viral envelope protein can prevent virus acquisition, reduce viremia, enhance immunity, and induce the killing of infected cells in animal models of HIV infection. Most importantly, some clinical trials have shown that bnMAbs could effectively d ecrease viremia and delay viral rebound in people chronically infected with HIV.Desde su primer aislamiento en 1983, el virus de la inmunodeficiencia humana (HIV) ha infectado a más de 77 millones de personas y solo se ha documentado un caso en el cual el virus fue removido completamente del organismo; aún resta confirmar un segundo caso informado recientemente. El tratamiento antirretroviral logra controlar la replicación viral en el plasma y en consecuencia recuperar (al menos parcialmente) la actividad del sistema inmune, con una notable reducción de la morbilidad y la mortalidad asociadas a la infección por HIV. Sin embargo, ante la dificultad para eliminar completamente el virus del organismo, es necesario continuar el tratamiento de por vida. Esto implica la exposició n a largo plazo a drogas antirretrovirales con riesgo de generar intolerancia, efectos tóxicos, brechas en la adherencia y selección de mutantes resistentes. Otro aspecto a considerar es la carga económica que implica tratar a 37 millones de personas infectadas con HIV, la mayoría de ellas en países que solo pueden afrontar esos costos con ayuda internacional. Por ello, hasta tanto se disponga de una vacuna capaz de prevenir la infección de todas las formas circulantes del HIV, es necesario desarrollar nuevas herramientas terapéuticas capaces de complementar y potenciar los efectos del tratamiento antirretroviral. Diversos ensayos preclínicos sugieren que la administración pasiva de anticuerpos monoclonales dirigidos contra la glicoproteína de envoltura viral podría prevenir la infección, reducir la carga viral, estimular la respuesta inmune y favorecer la eliminación de células infectadas con HIV.

Two-drug regimens (2DRs) can potentially reduce long-term cumulative drug exposure and decrease treatment-associated costs for HIV-1–infected individuals, who require lifelong therapy.1 The core antiretroviral agent in a 2DR must have high potency and a high barrier to resistance.1 As such, early studies investigating 2DRs as initial or maintenance therapy for HIV infection evaluated the pairing of the potent, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI) lamivudine with pharmacologically boosted protease inhibitors (PIs), which have a high barrier to resistance.2–6 Although noninferior efficacy was shown against 3-drug regimens (3DRs), PIs are associated with adverse metabolic effects, long-term toxicities, and drug–drug interactions, limiting their appeal as components of lifelong therapy.7,8 Thus, a need remains for well-tolerated, potent 2DRs with a high barrier to resistance. The integrase strand transfer inhibitor (INSTI) dolutegravir has a high barrier to resistance, making it a well-suited candidate for inclusion in a 2DR,9 particularly when paired with lamivudine,10 as previously observed.11,12 In primary week 48 analyses of the 2 phase III studies GEMINI-1 and GEMINI-2 in treatment-naive adults, dolutegravir + lamivudine was noninferior to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA

Supplemental Digital Content is Available in the Text., Background: Raltegravir 1200mg (2×600mg tablets) once daily (QD) demonstrated noninferior efficacy and similar safety to raltegravir 400mg twice daily (BID) at week 48 of the ONCEMRK trial. Here, we report the week 96 results from this study. Methods: ONCEMRK is a phase 3, multicenter, double-blind, noninferiority trial comparing raltegravir 1200mg QD with raltegravir 400mg BID in treatment-naive HIV-1–infected adults. Participants were assigned (2:1) to raltegravir 2×600mg QD or 400mg BID, both with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) for 96 weeks. Randomization was stratified by screening HIV-1 RNA and hepatitis B/C status. Efficacy was assessed as the proportion of participants with HIV-1 RNA 260 cells/mm3 from baseline in both groups. Resistance to raltegravir was infrequent, occurring in 0.8% of each treatment group through week 96. Adverse event rates were similar for the 2 regimens. Conclusions: In HIV-1–infected treatment-naive adults receiving FTC/TDF, raltegravir 1200mg QD demonstrated noninferior efficacy to raltegravir 400mg BID that was durable to week 96, with a safety profile similar to raltegravir 400mg BID.

Since 1996, triple-drug combinations consisting of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a ritonavir-boosted protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or recently, an integrase inhibitor have been considered the standard of care for treatment of HIV-infected individuals. As patients’ life expectancy has increased, an increasing rate of comorbidities has been reported. Cumulative toxicity and cost have become an important concern motivating new research exploring alternative antiretroviral treatment strategies. In different clinical trials, NRTI-sparing regimens have been explored in order to preserve effectiveness while reducing toxicity and potential costs. However, to date, class-sparing regimens have shown lower effectiveness than standard triple-drug therapy regimens in antiretroviral-naive patients. On the other hand, the use of dual therapy without certain nucleosides, such as tenofovir or zidovudine, was explored in the GARDEL trial consisting of the use of ritonavir-boosted lopinavir and lamivudine. This is the only large trial showing non-inferiority of dual therapy at 48 and 96 weeks compared to triple therapy. The improved potency, tolerability and durability, and fewer reported toxicities, of newer drugs with a higher resistance barrier paved the way for the evaluation of other class-sparing strategies, including monotherapy and dual therapies that are being applied as initial therapy or as a switch strategy in patients virologically suppressed on triple-drug regimens. The aim of the dual strategy is to achieve and maintain viral suppression, improve immunologic recovery, minimize short- and long-term adverse effects, and thereby improve adherence and potentially reduce costs.

Background In Argentina, HIV prevalence among transgender women (TGW) has been reported at 34%. The stigma is one of the most important factors limiting their access to healthcare services. The aims of this study were to compare different HIV testing methodologies, to determine the factors associated with HIV diagnosis and to determine the feasibility of a home-based HIV testing service for TGW. Methods A multidisciplinary team performed home-based HIV testing interventions in four cities of Argentina. Participants self-identified as TGW, older than 14 years and with a negative or unknown HIV status. Blood samples were screened by two rapid tests (RT), one based on antibodies (Determine™ HIV-1/2) and the other on antigen and antibodies (Determine™ HIV-1/2 Combo), and the subsequent blood processing via 4th generation ELISA (VIDAS HIV DUO). All reactive samples were confirmed with a viral load (VL). We compared the results of both RT with the ELISA. Samples were pooled in groups of 6 and a VL (Abbott Real Time) performed to identify acute HIV infections. Factors associated with HIV infection were evaluated with multivariate logistic regression analysis. Results A total of 260 TGW were tested, 51 tested positive (HIV prevalence 19.6%). There were no discordant results between both RTs nor between RTs and 4th generation ELISA, therefore the correlation was 100%. The VL identified 2 additional positive samples. The final analytic sample for positive cases consisted of 53 TGW. In the multivariate analysis, factors associated with a positive HIV result were history of other sexually transmitted infections (STIs) and not being previously tested for HIV. TGW tested for the first time were at 4 times greater risk of being HIV positive compared to those that were tested previously. Conclusions A multidisciplinary home-based HIV testing service among TGW is feasible and effective to detect cases of HIV infection. The testing algorithm should start with an RT followed by molecular diagnosis. The history of STIs and never having been tested for HIV were the factors associated with HIV-positive results and should determine efforts to reach this population. Home-based testing reaches individuals that were not tested before and who have more risk of acquiring HIV.

In HIV-1-infected patients, virological failure can occur as a consequence of the mutations that accumulate in the viral genome that allow replication to continue in the presence of antiretrovirals (ARVs). The development of treatment-emergent resistance to an ARV can limit a patient's options for future therapy, prompting the need for ARV regimens that are resilient to the emergence of resistance. The genetic barrier to resistance refers to the number of mutations in an ARV's therapeutic target that are required to confer a clinically meaningful loss of susceptibility to the drug. The emergence of resistance can be affected by pharmacological aspects of the ARV, including its structure, inhibitory quotient, therapeutic index, and pharmacokinetic characteristics. Dolutegravir (DTG) has demonstrated a high barrier to resistance, including when used in a two-drug regimen (2DR) with lamivudine (3TC). In the GEMINI-1 and GEMINI-2 studies, DTG +3TC was noninferior to DTG + emtricitabine/tenofovir disoproxil fumarate in treatment-naive participants, with similar proportions achieving HIV-1 RNA

Introduction HIV worsens HCV-related liver disease by accelerating fibrosis progression; however, progression rates are extremely variable among HIV/HCV-coinfected individuals. NK cells are associated with modulation of liver fibrosis and are profoundly altered during HCV and HIV infections. CD4+ T-cells modulate NK cell function, and are also affected by HIV infection. Here, we aim to characterize the association of hepatic fibrosis with both the phenotype and function of peripheral NK cells and their regulation by CD4+ T-cells, in HIV/HCV-coinfected individuals. Methods Thirty-four HIV/HCV-coinfected individuals with minimal (n = 16) and advanced (n = 18) fibrosis (METAVIR F0/F1 and F4 scores respectively) and 20 healthy volunteers were enrolled. PBMC were obtained from peripheral blood samples and NK and CD4+ T-cells were isolated and analysed. NK cell phenotype (CD25, CD69, Nkp46, NKG2D, PD-1), degranulation (CD107a) and IFN-γ and TNF-α production, as well as CD4+ T-cell activation (CD69, CD25 and CD38) were measured by flow cytometry. CD4+ T-cell conditioned medium (CM) derived from F0/F1 or F4 individuals was assessed for IL-2 levels by ELISA. Modulation of NK cell functionality by these CMs was also analysed. Results When comparing to NK cells from individuals with minimal fibrosis, degranulation and cytokine secretion by NK cells from subjects with F4 scores was significantly impaired, while PD-1 expression was augmented. On the one hand, neither the expression of activation markers nor IL-2 secretion was distinctly induced in CD4+ T-cells from subjects with F0/F1 or F4 METAVIR scores. Finally, NK cell degranulation and cytokine secretion were not differentially modulated by CD4+ T-cell CM, whether CD4+ T-cells derived from subjects with minimal or advanced fibrosis. Conclusions Low levels of NK and CD4+ T-cells in HIV/HCV-coinfected individuals with advanced liver fibrosis have been previously described. Here, we show that advanced liver fibrosis in coinfected individuals is associated to a defective function of NK cells and an increased expression of the exhaustion/senescence marker PD-1. This NK signature could not be attributed to changes in the ability of CD4+ T-cells to modulate NK cell function.

Los seres humanos tenemos un cierto fetichismo con los números redondos. Así, celebramos los 25 años de matrimonio de forma diferente a los 24 o los 26. Lo mismo sucede con los aniversarios de egresos escolares y universitarios, entre tantos otros acontecimientos. Quienes hacemos ASEI no somos la excepción y por eso preparamos esta edición especial para el número 100 de nuestra revista. Cuando comenzamos a trabajar en el número 1, recuerdo haber solicitado apoyo al representante de un organismo internacional, quien me desaconsejó continuar con la iniciativa, argumentando que “…muchas revistas publican el número 1, pero muy pocas llegan al número 100…”. Pero aquí estamos. A lo largo de estos 26 años, ASEI (originalmente Actualizaciones en sida) contó con prestigiosos colaboradores nacionales y extranjeros y el apoyo de la industria farmacéutica, sin los cuales hubiera sido imposible llevar adelante esta iniciativa destinada a contribuir a la educación médica de postgrado en idioma español. Sabemos que el “idioma oficial” del conocimiento científico es el inglés, pero también que muchos miembros del equipo de salud no se manejan con fluidez en esa lengua. De allí nuestra decisión de crear y mantener una publicación inicialmente centrada en HIV/sida en idioma español. Durante estos 26 años hemos mantenido la revista pese a los cambiantes momentos de la situación económica en Argentina. Más de una vez tuvimos que reducir el número de páginas, alterar el gramaje del papel o postergar una edición. Pero como escribimos en el editorial de un número publicado en plena crisis de 2002, decidimos salir adelante “con el pesimismo de la inteligencia y con el optimismo de la voluntad”, citando al pensador italiano Antonio Gramsci. La historia de la revista tuvo recientemente dos hitos que contribuyeron claramente a su evolución. El primero fue la alianza estratégica con SADI, que nos llevó a transformar Actualizaciones en sida en Actualizaciones en sida e infectología. Más allá del cambio de nombre, esta asociación amplió el espectro de temas publicados e incrementó el número de colaboradores, tanto de revisores como de autores. El segundo fue el reemplazo del papel por el formato digital, más accesible, costo-efectivo y ecológico. El sitio infectología.info alberga la revista y sus suplementos, además de otras informaciones valiosas para los interesados. Un especial reconocimiento para el comité editor, los secretarios de redacción, los revisores de trabajos y nuestros sponsors, que siguen apoyando esta iniciativa, hoy patrimonio conjunto de Fundación Huésped y SADI. Si bien ASEI está indexada en LATINDEX, nos queda la asignatura pendiente de ingresar en MEDLINE. Para hacerlo posible necesitamos contar con más artículos originales y por ello apelamos a nuestros colegas a ayudarnos en la consecución de este gran objetivo. Al respecto hemos implementado un sistema de tutoría sin cargo para ayudar a quienes tengan dificultades con la escritura, de modo de favorecer la publicación de sus trabajos. No duden en consultarnos. Convencidos de poder lograr nuestros objetivos, esperamos seguir celebrando muchos aniversarios más. Hacia allí vamos. Pedro CahnDirector Científico de Fundación HuéspedDirector de ASEI

Background A prespecified integrated safety analysis was conducted for 3 doravirine (DOR) double-blind trials (Phase IIb: P007 [NCT01632345]; Phase III: DRIVE-FORWARD [NCT02275780] and DRIVE-AHEAD [NCT02403674]). Methods DOR (100 mg) arms from these trials were compared with darunavir plus ritonavir (DRV+r) in DRIVE-FORWARD and efavirenz (EFV) in P007 and DRIVE-AHEAD. Background therapies were emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in P007; abacavir/lamivudine (ABC/3TC) or FTC/TDF in DRIVE-FORWARD; and 3TC/TDF for DOR and FTC/TDF for EFV in DRIVE-AHEAD. The primary endpoint was the proportion of participants discontinuing due to adverse events (AEs) through Week 48. Results Discontinuation rates due to AEs were similar for participants on DOR and DRV+r (2.5% vs 3.1%, respectively) and lower for those on DOR than for those on EFV (2.5% vs 6.6%, respectively). Rates of drug-related AEs for DOR, DRV+r, and EFV were 30.9%, 32.1%, and 61.4%, respectively. In an analysis of DOR versus EFV, the treatment difference for discontinuations due to AEs was −3.4%, favoring DOR (95% confidence interval −6.2 to −0.8; P = .012). Fewer participants experienced neuropsychiatric AEs on DOR than on EFV (25.0% vs 55.9%, respectively), and fewer experienced diarrhea on DOR than on DRV+r (12.4% vs 22.5%, respectively). Changes from baseline in most lipid parameters also favored DOR. Conclusions At Week 48, DOR at 100 mg had a favorable safety profile compared with EFV or DRV+r and a favorable tolerability profile compared with EFV.

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-naive 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-naive adults. Further study of dual treatment regimens is warranted.

Fil: Lopardo, Gustavo. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Lopardo, Gustavo. Fundación del Centro de Estudios Infectológicos; Argentina Fil: Belloso, Waldo H. Hospital Italiano de Buenos Aires. Department of Research; Argentina Fil: Nannini, Esteban. Sanatorio Británico. Departamento de Enfermedades Infecciosas; Argentina Fil: Nannini, Esteban. Consejo Nacional de Investigaciones Científicas y Tecnicas; Argentina Fil: Colonna, Mariana. Inmunova S.A; Argentina Fil: Sanguineti, Santiago. Inmunova S.A; Argentina Fil: Zylberman, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Zylberman, Vanesa. Inmunova S.A; Argentina Fil: Munoz, Luciana. Inmunova S.A; Argentina Fil: Dobarro, Martín. Sanatorio Sagrado Corazón; Argentina Fil: Lebersztein, Gabriel. Sanatorio Sagrado Corazón; Argentina Fil: Farina, Javier. Hospital de Alta Complejidad Cuenca Alta Néstor Kirchner; Argentina Fil: Vidiella, Gabriela. Sanatorio Agote; Argentina Fil: Bertetti, Anselmo. Sanatorio Güemes; Argentina Fil: Crudo, Favio. Hospital Municipal Emilio Zerboni; Argentina Fil: Crudo, Favio. Universidad Nacional de San Antonio de Areco; Argentina Fil: Alzogaray, María Fernanda. Instituto Medico Platense; Argentina Fil: Barcelona, Laura. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Teijeiro, Ricardo. Hospital General de Agudos Dr. Ignacio Pirovano; Argentina Fil: Lambert, Sandra. Hospital de Alta Complejidad El Cruce Néstor Kirchner; Argentina Fil: Scublinsky, Darío. Clínica Zabala; Argentina Fil: Iacono, Marisa. Hospital Provincial Neuquén Dr. Castro Rendón; Argentina Fil: Stanek, Vanina. Hospital Italiano de Buenos Aires. Servicio de Medicina Interna. Sección de Infectología; Argentina Fil: Solari, Ruben. Hospital de Infecciosas Francisco Javier Muñiz; Argentina Fil: Cruz, Pablo. Centro Gallego de Buenos Aires; Argentina Fil: Casas, Marcelo Martín. Clínica Adventista Belgrano; Argentina Fil: Abusamra, Lorena. Hospital Municipal Dr. Diego Thompson; Argentina Fil: Luciardi, Hector Lucas. Hospital Centro de Salud Zenón J. Santillán; Argentina Fil: Cremona, Alberto. Hospital Italiano La Plata; Argentina Fil: Caruso, Diego. Hospital Español; Argentina Fil: Miguel, Bernardo de. mAbxience; España Fil: Millan, Susana. mAbxience; España Fil: Kilstein, Yael. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Kilstein, Yael. Hospital Italiano de Buenos Aires. Department of Research; Argentina Fil: Pereiro, Ana. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Pereiro, Ana. Sanatorio Británico. Departamento de Enfermedades Infecciosas; Argentina Fil: Sued, Omar. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Sued, Omar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cahn, Pedro. Hospital Municipal Dr. Bernardo Houssay; Argentina Fil: Cahn, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Spatz, Linus. Inmunova S.A.; Argentina Fil: Goldbaum, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Goldbaum, Fernando. Inmunova S.A.; Argentina Fil: Goldbaum, Fernando. Fundación Instituto Leloir; Argentina Fil: Goldbaum, Fernando. Universidad Nacional de San Martín Campus Miguelete. Centro de Rediseño e Ingeniería en Proteínas; Argentina Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Tecnicas; Argentina Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Departamento de Docencia e Investigación; Argentina Fil: Pérez Lloret, Santiago. Universidad Abierta Interamericana. Centro de Altos Estudios en Ciencias Humanas y de la Salud; Argentina Abstract: Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65 1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5 28% [-3 95; 14 50]; p = 0 15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14 2 (§ 0 7) days in the INM005 group and 16 3 (§ 0 7) days in the placebo group, hazard ratio 1 31 (95% CI 1 0 to 1 74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6 9% the INM005 group and 11 4% in the placebo group (risk difference [95% IC]: 0 57 [0 24 to 1 37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Background Fostemsavir is a prodrug of temsavir, an attachment inhibitor that binds directly to HIV-1 gp120, blocking initial viral attachment and entry into host CD4+ T-cells. Efficacy, safety and dose-response data of fostemsavir in treatment-experienced, HIV-1-infected subjects, through week 48, are reported. Methods AI438011 is an ongoing Phase IIb, randomized, active-controlled trial (NCT01384734). Subjects were randomized 1:1:1:1:1 into five arms: fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily or 1,200 mg once daily) and a reference arm (ritonavir-boosted atazanavir [ATV/r] 300/100 mg once daily), each with a backbone of raltegravir 400 mg twice daily plus tenofovir disoproxil fumarate 300 mg once daily. Results In total, 251 subjects were treated. Through week 48, the proportion of fostemsavir subjects with HIV-1 RNA + T-cell count increases from baseline were 145-186 cells/μl and 142 cells/μl for the ATV/r arm. Fostemsavir doses were generally well tolerated and no fostemsavir-related adverse events led to discontinuation. Conclusions Through week 48, fostemsavir continued to be well tolerated and showed similar efficacy to ATV/r. These results support the ongoing Phase III trial in heavily treatment-experienced adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining). ClinicalTrials.gov identifer: NCT01384734.

Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understanding its role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC in HIV infection, abrogating its protective role. Plasma samples from 20 HIV-positive (HIV + ) subjects enrolled during primary HIV infection (PHI), 10 chronically infected subjects (chronic), and 7 elite controllers (EC) were used. ADCC was determined by using a fluorometric ADCC assay, before and after removal of plasma IgA. Data were analyzed by using nonparametric statistics. ADCC was documented in 80% of PHI enrollment samples and in 100% of PHI 12-month, chronic, and EC samples; it peaked after acute infection, reached a plateau in chronic infection, and decreased after initiation of antiretroviral treatment (ART). Significant associations between ADCC and disease progression were found only after removal of plasma IgA from 12-month PHI samples: the magnitude of ADCC not only increased after IgA removal but also correlated with CD4 + T-cell preservation. This work provides evidence that gp120-specific IgA was capable of modifying ADCC responses during natural HIV infection for the first time and adds to similar evidence provided in other settings. Furthermore, it underscores the complexity of the ADCC phenomenon and will help in an understanding of its underlying mechanisms. IMPORTANCE Although the induction of ADCC-mediating antibodies in HIV-infected subjects has been extensively documented, the association of these antibodies with protection from disease progression is poorly understood. Here, we demonstrate that plasma IgA is a factor capable of modifying the magnitude of IgG-mediated ADCC in HIV infection, mitigating its beneficial effect. These results help in understanding why previous studies failed to demonstrate correlations between ADCC and disease progression, and they also contribute to the notion that an HIV vaccine should stimulate the production of ADCC-mediating IgG antibodies but not IgA.

Introducción: 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

Purpose of review Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. Recent findings Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds. A phase 3 study showed a reduction in plasma viral RNA of 1.21-1.73 log10 copies/ml from baseline after 8 days of functional monotherapy; at 48 weeks, up to 82% of patients treated with FTR and an optimized background ARV regimen achieved virological suppression below 50 copies/ml. Summary FTR is an investigational HIV drug with a novel mechanism of action that demonstrates virologic activity in HIV-infected treatment-experienced individuals.

Summary The viral plasticity and the vast diversity of HIV-1 circulating strains necessitates the identification of new approaches to control this global pandemic. New generation broadly neutralising monoclonal antibodies (bnMAbs) against the HIV-1 viral envelope protein (Env) can prevent virus acquisition, reduce viraemia, enhance immunity, and induce the killing of infected cells in animal models of HIV-1 infection. Most importantly, passively administered bnMAbs are effective at decreasing viraemia and delaying viral rebound in people chronically infected with HIV-1. Single antibody treatment is associated with the emergence of viral escape mutants, and virus suppression is not maintained in the long term. However, a combination of bnMAbs and bioengineered multivalent antibodies that target different sites on Env might increase the efficacy of immunotherapy, adding a new relevant tool for clinical use. The aim of this Review is to highlight the potential benefits of this novel prophylactic and therapeutic approach to fight HIV-1.