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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....

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.

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.

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.

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

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.

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: 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.

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.

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.

Objectives To determine the impact of valaciclovir on HIV disease progression in treatment-naive HIV-positive adults. Methods In this fully blind, multicentre, 1:1 randomized placebo-controlled trial, treatment-naive HIV-1-positive adults with CD4 counts 400–900 cells/mm3 and not meeting contemporaneous recommendations for combination ART (cART) were randomized to valaciclovir 500 mg or placebo twice daily, and followed quarterly until having two consecutive CD4 counts ≤350 cells/mm3 or initiating cART for any reason. The primary analysis compared the rate of CD4 count decline by study arm after adjusting for baseline CD4 count and viral load (VL). Secondary analyses compared the rate of CD4 percentage decline, HIV VL, herpes simplex virus (HSV) recurrences and drug-related adverse events. The trial closed after release of the START trial results in August 2015. Results We enrolled 198 participants in Canada, Brazil, Argentina and the UK. Median (IQR) age was 35 (30–43) years. Baseline CD4 count was 592 (491–694) cells/mm3 and VL was 4.04 (3.5–4.5) log10 copies/mL. Over 276 person-years of follow-up, CD4 counts declined by 49 cells/mm3/year in the valaciclovir arm versus 58 cells/mm3/year in the placebo arm (P = 0.65). No differences were seen in the rate of change in CD4 percentage (−1.2%/year versus −1.7%/year, P = 0.34). VL was 0.27 log10 copies/mL lower in valaciclovir participants overall (P

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.

Background “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. Electronic supplementary material The online version of this article (10.1186/s13063-018-2758-5) contains supplementary material, which is available to authorized users.

Background DRIVE-FORWARD is a phase 3 trial with a completed double-blind period comparing doravirine (DOR) 100 mg with ritonavir-boosted darunavir (DRV/r) 800/100 mg, both administered with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs; tenofovir and emtricitabine, or abacavir and lamivudine), and an ongoing open-label extension. At Week (W) 48, DOR demonstrated non-inferior efficacy to DRV/r, with a superior lipid profile. Those results were sustained at W96. Here we present efficacy and safety results through W192. Methods Participants who completed the 96-week double-blind phase and met inclusion criteria were eligible to receive open-label DOR plus two NRTIs in a 96-week extension. Efficacy and safety at W192 were assessed in two groups: participants initially randomized to DOR and maintained on DOR (n=259) and those who switched from DRV/r to DOR at W96 (n=233). Results HIV-1 RNA < 50 copies/mL were maintained through W192 in 81.1% of participants who continued DOR and 80.7% of those who switched from DRV/r to DOR. The mean increase in CD4 T-cell counts from W96 to W192 was similar for participants maintained on DOR (47 cells/mm3) and those switched from DRV/r (53 cells/mm3). Protocol-defined virologic failure occurred in 3.1% and 5.6% of participants maintained on DOR and switched from DRV/r, respectively, and development of genotypic resistance was low in both groups (Table 1). Discontinuation due to adverse events was also low (Table 1). Fasting LDL-cholesterol, non-HDL-cholesterol, and triglycerides showed minimal increase in participants maintained on DOR and were reduced in those switched from DRV/r to DOR (Table 1). Participants maintained on DOR had minimal weight gain after W96 (median 1 kg), and a small increase overall (median 1.9 kg, Day 1 through W192); participants who switched to DOR had a small increase after W96 (median 1.5 kg), similar to the median weight gain in the base study (DOR 1.8 kg; DRV/r 0.7 kg). Conclusion Among participants who continued DOR in the DRIVE-FORWARD open-label extension, virologic suppression and favorable safety were maintained for an additional 96 weeks. Participants who switched from DRV/r to DOR maintained virologic suppression and demonstrated favorable safety for 96 weeks. Disclosures Pedro Cahn, MD, PHD, Merck (Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Kathleen Squires, MD, Merck (Employee) Sushma Kumar, PhD, Merck (Employee) Hong Wan, PhD, Merck (Employee) Valerie Teal, MS, Merck (Employee) Ernest Asante-Appiah, PhD, Merck (Employee) Peter Sklar, MD, Merck (Employee) Elizabeth A. Martin, DO, MPH, MBA, Merck (Employee) Rima Lahoulou, n/a, Merck (Employee)

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.

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

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.

The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level. Fil: Caruso, María Paula. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Falivene, Juliana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Holgado, María Pía. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Zurita, Diego Hernán(EXT). Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Laufer, Natalia Lorna. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Castro, Carina Lorena. Centro Médico Accord; Argentina Fil: Nico, Ángeles. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Maeto, Cynthia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Salido, Jimena Patricia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Perez, Hector. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Acevedo González, Horacio Anselmo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Cahn, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina. Fundación Huésped; Argentina Fil: Sued, Omar Gustavo. Fundación Huésped; Argentina Fil: Fink, Valeria Irene. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina. Fundación Huésped; Argentina Fil: Turk, Gabriela Julia Ana. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Gherardi, Maria Magdalena. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

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.

Background: Recent studies indicate that there is selection bias for transmission of viral polymorphisms associated with higher viral fitness. Furthermore, after transmission and before a specific immune response is mounted in the recipient, the virus undergoes a number of reversions which allow an increase in their replicative capacity. These aspects, and others, affect the viral population characteristic of early acute infection. Methods: 160 single gag-gene amplifications were obtained by limiting-dilution RT-PCR from plasma samples of 8 ARV-naïve patients with early acute infection (

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.