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COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.LifeArc and CW+.

Introduction Hematologic abnormalities are frequent among persons living with HIV (PLWH). The bone marrow aspirate (BMA) and biopsy (BMB) are commonly performed in the diagnostic approach of patients with unexplained cytopenias. Changes in antiretrovirals, supportive therapy and increased life expectancy have modified the distribution and etiology of cytopenias, questioning their use. Our aim was to analyze the diagnostic yield of BMA, BMB and marrow cultures for the evaluation of cytopenias in PLWH. Methods This was a retrospective cohort of ≥ 18-year-old PLWH undergoing bone marrow assessment (MA) for the evaluation of cytopenias between January 2002 and December 2015. Results A total of 236 cytopenic events were analyzed, 47.9% being PLWH who had a longstanding diagnosis (≥ 1 year). Adherence to antiretrovirals was 63.5%. Anemia was seen in 91.9% and pancytopenia in 39%. Common presentations included fever (52.1%), weight loss (42.8%) and adenopathies (28.8%). Median days from detection to MA was 5 (0 – 63 days). Most common etiologies were non-HIV infectious diseases (31.4%) and benign/malignant hematologic diseases (26.3%). The diagnostic yield was 16.1% for BMA, 20.3% for BMB, 30.5% for both and 35.6% when cultures were added. Patients most likely to have conclusive MA were those with moderate/severe thrombocytopenia (p = 0.007). Fever, splenomegaly, and low CD4+ counts were associated with infectious etiologies, while hematologic diagnoses were related to the presence of adenopathies. Conclusion As a minimally invasive intervention, the MA has a high yield for identifying the etiology of cytopenic events in PLWH, being conclusive in one in three patients. Early performance could lead to prompt diagnosis and timely therapy initiation.

INTRODUCTION Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID-19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. METHODS From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence (

Objectives To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naive patients using data from randomized controlled clinical trials. Methods We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naive people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. Results We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. Conclusion The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naive patients is similar to that of TT.

OBJECTIVES: To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials. DESIGN: We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk. METHODS: People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4 + cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4 + cell count less than 350 cells/μl vs. CD4 + cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization. RESULTS: Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care. CONCLUSION: Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.

Living with HIV has been proposed as a risk factor for the early development of functional decline. Composite marker tools like the Veterans Aging Cohort Study (VACS) Index, which includes HIV-associated and non-HIV-related markers of disease may better reflect multiorgan system injury and potentially predict functional outcomes. Therefore, the objective of this work is to determine whether higher VACS 2.0 Index scores predicts functional decline among older adults living with HIV (OALWH). Longitudinal study, including 131 adults ages 50 or older who underwent a comprehensive geriatric assessment at baseline and follow-up, at least a year apart. Functional status was determined by the gait speed (seconds for a 4-m distance). Linear regression models were constructed to determine the relationship between VACS 2.0 Index at baseline with gait speed at follow-up adjusted for potential confounders. The median for age was 58.0 years (range 50-84), and 81.7% were male. At baseline, the median VACS 2.0 Index score was 50.4 (interquartile range 42.2-65.3). The adjusted linear regression analysis found that higher baseline VACS 2.0 Index scores were significantly associated with a decline in gait speed (

Objectives Early initiation of antiretroviral therapy (ART) during acute HIV infection is associated with favourable clinical and epidemiological outcomes. Barriers to prompt treatment initiation limit the benefits of universal access to ART in Mexico. We sought to create an algorithm for the immediate detection and treatment of patients with acute HIV infection. Methods A nationwide cohort of patients with acute HIV infection was created in 2015. In order to identify cases and treat them promptly at our centre, an interdisciplinary group coordinated through an instant-messaging tool using smart phones was established. When a probable case was detected, a discussion was initiated to confirm the diagnosis and facilitate the administrative processes to initiate ART as soon as possible. We compared time to ART initiation with that in a comparison group of patients with chronic HIV infection enrolled during the same period (May 2015 to February 2017) through routine care, using survival analysis estimators and log-rank tests. Results We recruited 29 patients with acute HIV infection. The median time to ART initiation was 2 days in these patients, in contrast to 21 days for patients with chronic infection. There were no significant differences in the percentages of patients engaged in care, on treatment or virologically suppressed at 1 year of follow-up. Conclusions Implementing immediate ART initiation programmes is feasible in Mexico, in spite of the substantial administrative barriers that exist in the country. More extensive replication of this model in other centres and in patients with chronic infection is warranted to evaluate its effect on the continuum of care.

Background There are few data on life expectancy gains among people living with HIV in low-income and middle income settings where antiretroviral therapy (ART) is increasingly available. We aimed to analyse life expectancy trends from 2003 to 2017 among people with HIV beginning treatment with ART within the Caribbean, central America, and South America. Methods We did a multisite retrospective cohort study and included people with HIV who had started treatment with ART and were aged 16 years or older between Jan 1, 2003, and Dec 31, 2017, from Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru, who contributed person-time data from the age of 20 years until date of death, last contact, database closure, or Dec 31, 2017. We used the Chiang method of abridged life tables to estimate life expectancy at age 20 years for three eras (2003 & ndash;08, 2009 & ndash;12, and 2013 & ndash;17) overall and by demographic and clinical characteristics at ART initiation. We used Poisson regression models to weight mortality rates to account for informative censoring. Findings 30 688 people with HIV were included in the study; 17 491 (57 & middot;0%) were from the Haiti site and 13 197 (43 & middot;0%) were from all other sites. There were 2637 deaths during the study period: 1470 in Haiti and 1167 in other sites. Crude and weighted mortality rates decreased among all age groups over calendar eras. From 2003 & ndash;08 to 2013 & ndash;17, overall life expectancy for people with HIV at age 20 years increased from 13 & middot;9 years (95% CI 12 & middot;5 & ndash;15 & middot;2) to 61 & middot;2 years (59 & middot;0 & ndash;63 & middot;4) in Haiti and from 31 & middot;0 years (29 & middot;3 & ndash;32 & middot;8) to 69 & middot;5 years (67 & middot;2 & ndash;71 & middot;8) in other sites. Life expectancies at the end of the study period were within 10 years of those of the general population (69 & middot;9 years in Haiti and 78 & middot;0 years in all other sites in 2018). Disparities in life expectancy among people with HIV by sex or HIV transmission risk factor, CD4 cell count, level of education, and history of tuberculosis at or before ART initiation persisted across calendar eras. Interpretation Life expectancy among people with HIV receiving ART has significantly improved in Latin America and the Caribbean. Persistent disparities in life expectancy among people with HIV by demographic and clinical factors at ART initiation highlight vulnerable populations in the region Antecedentes: Las ganancias en la expectativa de vida de las personas viviendo con VIH asociados al incremento en la disponibilidad del tratamiento antirretroviral (TARV) en países de bajos y medianos ingresos ha sido poco estudiada hasta ahora. Nuestro objetivo fue analizar las tendencias en expectativas de vida en personas que iniciaron TARV entre 2003 y 2017 en el Caribe, Centro y Suramérica. Métodos: Analizamos de manera retrospectiva una cohorte multicéntrica de personas con VIH que iniciaron TARV a los 16 años (o mayores) entre el 1º de enero de 2003 y el 31 de diciembre de 2017 en sitios de atención en Argentina, Brasil, Chile, HaitíHonduras, México y Perú, que participan en la Red para el estudio de la Epidemiología en el Caribe, Centro y Suramérica (CCASAnet) y que hubieran contribuido con información de tiempo en seguimiento a partir de los 20 años de edad hasta la muerte, el fin del seguimiento, el cierre administrativo de la cohorte o el 31 de diciembre del 2017. Utilizamos el método de Chiang para analizar tablas de vida abreviadas para estimar la expectativa de vida a los 20 años para tres períodos de tiempo (2003–08, 2009–12 y 2013–17) de manera general y de acuerdo con características demográficas y clínicas al inicio de la TARV. Usamos modelos de regresión de Poisson para estimar las tasas de mortalidad ponderadas considerando la censura informativa. Hallazgos: Se incluyeron 30 688 personas con VIH: 17 491 (57·0%) del sitio en Haití y 13 197 (43·0%) del resto. Se registraron 2637 muertes durante el período de observación: 1470 en Haití y 1167 en los demás sitios. Las tasas de mortalidad, tanto no ajustadas como las ponderadas, se redujeron en todos los grupos de edad a lo largo de los tres períodos estudiados. La expectativa de vida general a los 20 años en las personas con VIH incrementó de 13·9 años (95% CI 12·5–15·2) en el período 2003–08 a 61·2 años (59·0–63·4) en Haití y de 31·0 (29·3–32·8) a 69·5 años (67·2–71·8) en los demás sitios. La expectativa de vida en el último período del estudio esta dentro de un rango de 10 años de diferencia con la población general (69·9 años en Haití y 78·0 años en los países de los otros sitios, en 2018). Las diferencias en la expectativa de vida en las personas con VIH de acuerdo con la vía de transmisión, el conteo de CD4, nivel educativo y antecedente de tuberculosis antes o al inicio de la TARV persistieron durante los tres períodos de estudio. Interpretación: La expectativa de vida en las personas con VIH que iniciaron TARV mejoró significativamente en América Latina y el Caribe. La persistencia de desigualdades en la expectativa de vida en las personas con VIH de acuerdo con factores sociodemográficos y clínicos resaltan la vulnerabilidad de algunas grupos en la región.

Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment., Author summary Histoplasmosis, an infection caused by Histoplasma capsulatum, is prevalent in the Americas, it is a common cause of pulmonary acute disease in cave explorers, speleologists, boy scouts and some other people in circumstantial risk, in most of these people the infection is commonly self-limited. However, in people living with HIV (PLWHIV) this infection might be acquired without specific exposition and it behaves like a severe disease with high fever, consumption, septic shock and death. Thus, there is a need for rapid and accurate methods for diagnosis in this population at risk. We tested five different methods for rapid diagnosis (three based on antigen detection in urine and two molecular assays based on PCR amplification, widely used) of disseminated histoplasmosis and we were able to demonstrate that two urine antigen detection tests (clarus Histoplasma GM Enzyme Immunoassay kit and MiraVista Histoplasma Urine Antigen LFA) showed excellent performance to diagnose of disseminated histoplasmosis in PLWHIV. The antigen detection tests have advantages over the PCR tests, their performance is higher, they are commercial standardized tests, easy to perform, and provide results in hours, therefore the integration of these tests in clinical laboratories will certainly impact on early diagnosis/treatment and consequently on the outcome of patients.

Background The Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán is a teaching hospital which was converted into a Coronavirus disease 2019 (COVID-19) designated hospital on mid-March 2020. In Mexico City, the COVID-19 peak started in mid-April 2020. A considerable proportion of those diagnosed with SARS-CoV-2 infection were treated by ambulatory care. We aimed to describe the clinical characteristics at diagnosis of ambulatory patients diagnosed with COVID-19, their willingness to donate plasma and their clinical outcomes at one month of the follow-up call program implementation. Methods A call strategy follow-up program (FUP) was established on April 19, 2020. All ambulatory patients received at least 3 calls every 48–72 hours, followed by 2 weekly calls. A team of voluntary medical students, general practitioners, fellows, and medical specialists was assembled for this purpose. Signs of alarm (fever >72 hours, shortness of breath, respiratory insufficiency) and other clinical signs were collected on every call. Willingness to donate plasma and possibility of a correct home isolation were also addressed. Results From April 19 to May 18, 2020, a total of 360 patients tested positive for SARS-CoV2, of whom 350 were followed. Their median age was 44 years (33–51), and 55% were female. 145 (41%) had completed all FUP calls and 194 (55%) referred to be asymptomatic in their last call. We identified 8 patients with signs of alarm during the calls, and 2 of them required hospitalization. During the FUP, 66% referred fatigue that limited their activities, 56% anosmia or dysgeusia, 32% headache, and 22% diarrhea. 90% were capable to properly isolate in their homes. Willingness to donate plasma was assessed in 89 patients, of whom, 75 (84%) manifested their willingness to donate. Conclusion Ambulatory follow-up is feasible and effective to identify those in need of hospitalization. Remarkably, half of the ambulatory patients had no comorbidities and presented anosmia/dysgeusia as the most frequent symptoms during follow-up. Willingness to donate plasma was high in this cohort. Disclosures All Authors: No reported disclosures

Invasive pulmonary aspergillosis (IPA) is a severe infection caused by aspergillus sp. that usually develops in patients with severe immunosuppression. IPA has been recently described in critically ill COVID-19 patients (termed as COVID-associated pulmonary aspergillosis, or CAPA) that are otherwise immunocompetent. In order to describe the characteristics of patients with CAPA, we conducted a retrospective cohort study in a tertiary care center in Mexico City. We included all patients with confirmed COVID-19 admitted to the intensive care unit that had serum or bronchoalveolar lavage galactomannan measurements. We used the criteria proposed by Koehler et al. to establish the diagnosis of CAPA. Main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital mortality. Out of a total of 83 hospitalized patients with COVID-19 in the ICU, 16 (19.3%) met the criteria for CAPA. All patients diagnosed with CAPA required IMV whereas only 84% of the patients in the non-IPA group needed this intervention (P = 0.09). In the IPA group, 31% (n = 5) of the patients died, compared to 13% (n = 9) in the non-CAPA group (P = 0.08). We conclude that CAPA is a frequent co-infection in critically ill COVID-19 patients and is associated with a high mortality rate. The timely diagnosis and treatment of IPA in these patients is likely to improve their outcome. Lay Summary We studied the characteristics of patients with COVID-19-associated invasive pulmonary aspergillosis (CAPA). Patients with CAPA tended to need invasive mechanical ventilation more frequently and to have a higher mortality rate. Adequate resources for its management can improve their outcome

Because high frequency and late presentation of HIV disease in our population, we decided to explore the presence of myocarditis among people with HIV-infection and advanced immunosuppression (less than 200 CD4+ cells/μL), and to describe the inflammatory changes observed after combined antiretroviral therapy (cART) initiation in an observational, longitudinal, prospective cohort performing cardiovascular MRI (cMRI) and doppler trans-thoracic echocardiogram (TTE).

Background We evaluated the risk of death for health-care workers (HCW) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Mexico City during the coronavirus disease 2019 (COVID-19) pandemic, and describe the associated factors in hospitalized HCW, compared with non-HCW. Methods We analyzed data from laboratory-confirmed SARS-CoV-2 cases registered from 27 February–31 August 2020 in Mexico City’s public database. Individuals were classified as non-HCW or HCW (subcategorized as physicians, nurses, and other HCW). In hospitalized individuals, a multivariate logistic regression model was used to analyze the potential factors associated with death and compare mortality risks among groups. Results A total of 125 665 patients were included. Of these, 13.1% were HCW (28% physicians, 38% nurses, and 34% other HCW). Compared with non-HCW, HCW were more frequently female, were younger, and had fewer comorbidities. Overall, 25 771 (20.5%) were treated as inpatients and 11 182 (8.9%) deaths were reported. Deaths in the total population (9.9% vs 1.9%, respectively; P Conclusions HCW represent an important proportion of individuals with SARS-CoV-2 infection in Mexico City. While the mortality risk is lower in HCW compared to non-HCW, a high mortality rate in hospitalized patients was observed in this study. Among HCW, nurses had a lower risk of death compared to physicians and other HCW.

INTRODUCTION: Kaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART). METHODS: Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression. RESULTS: Of 25 981 PWH, 481 had incident KS, including 200 ART-naïve and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation. CONCLUSIONS: KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.

espanolAntecedentes: la informacion regional sobre las caracteristicas de los pacientes con enfermedad por coronavirus (COVID) -19 es necesaria para una mejor comprension de la pandemia. Objetivo: El objetivo del estudio es describir las caracteristicas clinicas de los pacientes con COVID-19 diagnosticados en un centro de atencion terciaria en la Ciudad de Mexico y evaluar las diferencias segun el ambito del tratamiento (ambulatorio versus hospitalario) y la necesidad de cuidados intensivos ( IC). Metodos: Realizamos una cohorte prospectiva, que incluyo pacientes consecutivos con COVID-19 desde el 26 de febrero de 2020 hasta el 11 de abril de 2020. Resultados:Se identificaron 309 pacientes (140 pacientes hospitalizados y 169 pacientes ambulatorios). La mediana de edad fue de 43 anos (rango intercuartilico, 33-54), 59,2% varones y 18,6% trabajadores sanitarios (12,3% de nuestro centro). La mediana del indice de masa corporal (IMC) fue de 29,00 kg / m2 y el 39,6% tenia obesidad. En comparacion con los pacientes ambulatorios, los pacientes hospitalizados eran de mayor edad, tenian comorbilidades, tos y disnea con mayor frecuencia. Veintinueve (20,7%) pacientes hospitalizados requirieron tratamiento en la unidad de CI (UCI). Los antecedentes de diabetes (tipo 1 o 2) y el dolor abdominal fueron mas comunes en los pacientes de la UCI en comparacion con los pacientes que no estaban en la UCI. Los pacientes de la UCI tenian IMC mas altos, frecuencias respiratorias mas altas y saturaciones de oxigeno capilar de aire ambiente mas bajas. Los pacientes de la UCI mostraron una respuesta inflamatoria mas severa segun lo evaluado por el recuento de globulos blancos, recuento de neutrofilos y plaquetas, proteina C reactiva, ferritina, procalcitonina y niveles de albumina. Conclusiones: Los pacientes con comorbilidades, ya sean obesos de mediana edad o ancianos que se quejan de fiebre, tos o disnea, fueron mas propensos a ser ingresados. Al ingreso, los pacientes con diabetes, IMC alto y hallazgos clinicos o de laboratorio compatibles con un estado inflamatorio severo tenian mas probabilidades de requerir IC. EnglishBackground: Regional information regarding the characteristics of patients with coronavirus disease (COVID)-19 is needed for a better understanding of the pandemic. Objective: The objective of the study to describe the clinical features of COVID-19 patients diagnosed in a tertiary-care center in Mexico City and to assess differences according to the treatment setting (ambulatory vs. hospital) and to the need of intensive care (IC). Methods: We conducted a prospective cohort, including consecutive patients with COVID-19 from February 26, 2020 to April 11, 2020. Results: We identified 309 patients (140 inpatients and 169 outpatients). The median age was 43 years (interquartile range, 33-54), 59.2% men, and 18.6% healthcare workers (12.3% from our center). The median body mass index (BMI) was 29.00 kg/m2 and 39.6% had obesity. Compared to outpatients, inpatients were older, had comorbidities, cough, and dyspnea more frequently. Twenty-nine (20.7%) inpatients required treatment in the IC unit (ICU). History of diabetes (type 1 or 2) and abdominal pain were more common in ICU patients compared to non-ICU patients. ICU patients had higher BMIs, higher respiratory rates, and lower room-air capillary oxygen saturations. ICU patients showed a more severe inflammatory response as assessed by white blood cell count, neutrophil and platelet count, C-reactive protein, ferritin, procalcitonin, and albumin levels. By the end of the study period, 65 inpatients had been discharged because of improvement, 70 continued hospitalized, and five had died. Conclusions: Patients with comorbidities, either middle-age obese or elderly complaining of fever, cough, or dyspnea, were more likely to be admitted. At admission, patients with diabetes, high BMI, and clinical or laboratory findings consistent with a severe inflammatory state were more likely to require IC.

Background In resource-constrained settings, many people with HIV (PWH) are treated for tuberculosis (TB) without bacteriologic testing. Their mortality compared with those with bacteriologic testing is uncertain. Methods We conducted an observational cohort study among PWH ≥15 years of age initiating TB treatment at sites affiliated with 4 International epidemiology Databases to Evaluate AIDS consortium regions from 2012 to 2014: Caribbean, Central and South America, and Central, East, and West Africa. The exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard of death in the 12 months after TB treatment initiation was estimated using a Cox proportional hazard model. Missing covariate values were multiply imputed. Results In 2091 PWH, median age 36 years, 53% had CD4 counts ≤200 cells/mm3, and 52% were on antiretroviral therapy (ART) at TB treatment initiation. The adjusted hazard of death was higher in patients with no test compared with those with positive test results (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.08–2.26). The hazard of death was also higher among those with negative compared with positive tests but was not statistically significant (HR, 1.28; 95% CI, 0.91–1.81). Being on ART, having a higher CD4 count, and tertiary facility level were associated with a lower hazard for death. Conclusions There was some evidence that PWH treated for TB with no bacteriologic test results were at higher risk of death than those with positive tests. Research is needed to understand the causes of death in PWH treated for TB without bacteriologic testing.

Introduction In 2013, the World Health Organization (WHO) recommended initiating combination ART (cART) in all adults with HIV and CD4+ lymphocyte counts (CD4)

Background The main risk factors for severe COVID-19 described are diabetes, hypertension, cardiovascular disease, obesity, chronic lung and renal disease. HIV infection has not been found to be an independent factor for severe COVID-19, however, only small case series of HIV and COVID-19 have been reported. The aim of this study is to describe clinical characteristics and outcomes of HIV positive patients with COVID-19 hospitalized in a tertiary care hospital in Mexico City. Methods A single-center review of HIV-infected patients diagnosed with COVID-19 was performed using medical records from March 1st, 2020 to May 20th, 2020. We describe the clinical characteristics and outcomes Results A total of 11 PLWH were diagnosed with COVID-19, only 9 were hospitalized and are described here. One died, 6 were discharged and 2 remain hospitalized (table 1). Overall, the median age was 46 years, all males and most (7/9) were on INSTI based ART regimen and undetectable HIV viral load (9/9), with a median of CD4 counts of 581 cell/mm3. The median days since onset of COVID19 symptoms was 7 days. 6/9 had at least one comorbidity: hypertension (3/9) and chronic kidney disease (3/9). 7/9 had body max index >25. 7/9 had moderate to severe lung disease, evidenced by computed tomography. 4/9 required invasive mechanical ventilation, and all were successfully extubated. Table 1. Characteristics and outcomes * Conclusion Most of the HIV patients who required hospitalization due to COVID19 had comorbidities. In spite of severe and critical presentations, most patients have recovered. Outcomes appear no different from those seen for non-HIV infected patients, however larger studies to determine the risk that HIV infection confers to COVID19 outcomes are needed. Disclosures All Authors: No reported disclosures

Background Among 230,000 people living with HIV in Mexico, 24% are unaware of their diagnosis, and half of newly diagnosed individuals are diagnosed with advanced disease. Early diagnosis is the goal to mitigate HIV epidemic. Missed opportunities may reflect a lack of clinicians’ consideration of HIV screening as part of routine medical care. We assessed whether an educational intervention on residents was effective to 1) improve the knowledge on HIV screening; 2) increase the rate of HIV tests requested in the hospitalization floor (HF) and the emergency department (ED); and 3) increase HIV diagnosis in HF and ED. Methods Internal Medicine and Surgery residents at a teaching hospital were invited to participate. The intervention occurred in August 2018 and consisted in 2 sessions on HIV screening with an expert. A questionnaire was applied before (BQ) and after (AQ) the intervention, which included HIV screening indications and clinical cases. The Institutional Review Board approved this study. Written informed consent was obtained from all participants. BQ and AQ scores were compared with a paired t-test. To evaluate the effect on HIV test rate in the HF and ED, an interrupted time series analysis was performed. Daily rates of tests were obtained from September 2016 to August 2019 and plotted along time. Restricted cubic splines (RCS) were used to model temporal trends. HIV diagnosis in HF and ED pre- and post-intervention were compared with a Fisher’s exact test. A p< 0.05 was considered significant. Results Among 104 residents, 57 participated and completed both questionnaires. BQ score was 79/100 (SD±12) and AQ was 85/100 (SD±8), p< .004. Time series of HIV testing had apparent temporal trends (Fig 1). HIV test rate in the HF increased (7.3 vs 11.1 per 100 episodes) and decreased in the ED (2.6 vs 2.3 per 100 episodes). HIV diagnosis increased in the HF, from 0/1079 (0%) pre-intervention to 5/894 (0.6%) post-intervention (p< .018) (Table 1). Fig 1. HIV test rates. Gray area represents post-intervention period. Table 1. Description of episodes, HIV tests and rates pre- and post-intervention in the Emergency Department and Hospitalization Floor. Conclusion A feasible educational intervention improved residents’ knowledge on HIV screening, achieved maintenance of a constant rate of HIV testing in the HF and increased the number of HIV diagnosis in the HF. However, these results were not observed in the ED, where administrative barriers and work overload could hinder HIV screening. Disclosures All Authors: No reported disclosures

Background An elevated incidence of invasive pulmonary aspergillosis (IPA) in patients with COVID-19 without traditional risk factors for IPA has been recently reported around the world. This co-infection has been described in patients requiring treatment in an intensive care unit. The risk factors for its development are still unclear. Methods We conducted a nested case-control study using the COVID-19 registry of the ARMII study group, based in the Centro Médico ABC, a private hospital in Mexico City. We included all patients that required admission to the intensive care unit (ICU) from March 12 to June 15, 2020, and excluded patients without serum galactomannan measurements or bronchial secretion cultures. We used the modified definition of IPA proposed by Schauwvlieghe et al for IPA in influenza patients. The control group was formed by patients with ruled-out IPA (negative galactomannan and secretion cultures). We compared both groups to identify risk factors for IPA using the chi-squared test or the Mann-Whitney U test as applicable. Results Out of a total 239 patients, 54 met the inclusion criteria. We identified 13 patients with IPA (24.07%) that met the definition of IPA (2 with positive cultures and 11 with positive galactomannan) and 41 without IPA. Only three patients with IPA had important comorbidities (COPD, chronic kidney disease, and HIV). Patients with IPA tended to have a higher median age (64.6 vs 53.59, p=0.075) and a higher serum glucose at their arrival (145 vs 119, p=0.028). All patients with IPA presented to the hospital with ARDS (100% vs 72.5%, p=0.034), but ultimately did not have a higher requirement for mechanical ventilation (100% vs 82.93%, p=0.110). There were no statistical significant differences in use of Tocilizumab, use of glucocorticoids, mortality (23.07% vs 17.50%, p=0.563) or length of stay. Conclusion It has been previously described that patients with acute respiratory disease syndrome triggered by viral infection, like the influenza virus, are prone to invasive aspergillosis even in the absence of underlying immunodeficiency. The use of antifungals to prevent aspergillosis in COVID-19 patients should be assessed because of the gravity presented in the patients with this co-infection. Disclosures All Authors: No reported disclosures

Background: In Mexico, mortality in people with HIV (PWHIV) remained constant after the expansion of ART access. Information regarding specific causes of deaths and whether related or not to AIDS may provide further comprehension on the roots of this pattern. We estimated the unadjusted and adjusted frequencies of specific causes of deaths in people with HIV occurring in Mexico early after their diagnosis and describe specific causes of death over a 10-year period. Methods: Using National Death Registry data, we identified all deaths among PWHIV during 2004-2015. We defined late mortality (LM) as deaths occurring after one year of HIV-diagnosis, early mortality (EM) as deaths occurring within the first year, and very early mortality (VEM) as those occurring within the first month after HIV-diagnosis. We describe the frequency of specific causes of death, of AIDS-related deaths, and of EM and VEM by calendar-year and explore factors associated to AIDS-related deaths. Findings: There were 59,650 deaths in PWHIV: 48,797 (82%) in men; 47% of deaths were AIDS-related, 56% were EM, and 18% VEM. The probability of AIDS-related deaths decreased from 57% in 2004 to 48% in 2010, but remained constant afterwards. Over time, deaths due to unspecified pneumonia, infectious diseases not definitory of AIDS proportionally increased. Early (EM) and VEM deaths were more likely to be AIDS-related, when compared to LM. Interpretation: Persistent EM, increasing VEM, and constant frequency of AIDS-related deaths strongly suggest that persistence of late HIV-diagnosis in Mexico substantially contributes to lower than expected reductions in AIDS-related mortality. Non-AIDS associated deaths are a small proportion, with modest increases recently in cerebral/myocardial vascular events, renal disorders, and non-AIDS-defining neoplasias. These results indicate that policy efforts should be directed to expand HIV-diagnosis and early linkage to care. Funding Statement: This work was partially supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet), a member of the International Epidemiologic Databases to Evaluate AIDS (leDEA) (U01AI069923). Declaration of Interests: Yanink Caro-Vega, Pablo F Belaunzaran-Zamudio, Brenda Crabtree-Ramirez, Jesus Alegre-Diaz, Raul Ramirez-Reyes, Pablo Kuri- Morales, Malaquias Lopez-Cervantes have no conflicts to declare. Juan. Sierra- Madero reports personal fees and non-financial support from Gilead, non-financial support from MSD, grants from BMS, grants from Pfizer, personal fees from Jansen all outside the submitted work. Ethical Approval Statement: Not required.

Background The Histoplasma urine antigen (HUAg) is the preferred method to diagnose progressive disseminated histoplasmosis (PDH) in HIV patients. In 2007, IMMY ALPHA Histoplasma EIA was approved for clinical for on-site use, and therefore useful for regions outside the United States. However, ALPHA-HUAg is considered inferior to the MVista-HUAg which is only available on referral. We aim to evaluate the diagnostic accuracy of ALPHA-HUAg. Methodology/Principal findings We conducted a multicenter, prospective, diagnostic test study in two secondary and eight tertiary-care facilities in Mexico. We included HIV patient with PDH suspicion and evaluated ALPHA-HUAg diagnostic accuracy using as reference standard the Histoplasma capsulatum growth on blood, bone marrow, and tissue cultures or compatible histopathologic exam (PDH–proven). We evaluated the results of 288 patients, 29.5% (85/288; 95% confidence interval [CI], 24.3–35.1) had PDH. The sensitivity of ALPHA-HUAg was 67.1% (95% CI, 56–76.8%) and the specificity was 97.5% (95% CI, 94.3%-99.1%). The positive likelihood ratio was 27.2 (95% CI; 11.6–74.4). In 10.5% of the PDH–proven patients, a co-existing opportunistic infection was diagnosed, mostly disseminated Mycobacterium avium complex infection. Conclusions/Significance We observed a high specificity but low sensitivity of IMMY-HUAg. The test may be useful to start early antifungals, but a culture-based approach is necessary since co-infections are frequent and a negative IMMY-HUAg result does not rule out PDH., Author summary Histoplasmosis is an endemic mycosis in many regions of Latin America. In the HIV population it manifests as progressive disseminated histoplasmosis (PDH), an entity hard to diagnose since the causative fungi—Histoplasma capsulatum—is slow growing and requires advance biosafety for its handling. As an alternative, the diagnosis can be made by detecting the histoplasma urinary antigen, but only one kit is commercially available outside the US. We evaluated this kit (IMMY ALPHA Histoplasma EIA) among HIV patients with suspected and found a high specificity but low sensitivity (i.e., a positive histoplasma urine antigen is almost unequivocal, but a negative result does not rule out the PDH). However, we believe the test is useful since the positive likelihood rates show that a patient with PDH is 27 times more likely to have an IMMY-HUAg positive result; this may allow early targeted treatment.

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (

Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case–control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient’s mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome. Trial Registration: ClinicalTrials.gov NCT02264509.

Background The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to “crowding out” of sicker patients. Methods and findings We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/μL [145 sites in 22 countries] and CD4 ≤ 500 cells/μL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after expansion to CD4 ≤ 500), with no change or small increases among those eligible under prior guidelines (CD4 ≤ 350: −0.6 pp, 95% CI −2.0 to 0.7 pp; CD4 ≤ 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility expansion to CD4 ≤ 500, changes in CI-ART were largest among younger patients (16–24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack of a counterfactual and difficulty accounting for secular outcome trends, due to universal exposure to guideline changes in each country. Conclusions These findings underscore the potential of ART eligibility expansion to improve the timeliness of ART initiation globally, particularly for young adults., In a large-scale analysis, Olga Tymejczyk and colleagues study antiretroviral therapy initiation in people with HIV infection accompanying secular changes in treatment eligibility., Author summary Why was this study done? In 2009 and 2013, the World Health Organization (WHO) recommended that HIV patients with CD4 counts ≤350 and ≤500 cells/μL, respectively, initiate antiretroviral treatment (ART). The expansion of ART eligibility criteria has the potential to increase ART initiation rates, especially among healthier patients; however, it could also lead to “crowding out” of persons with more advanced disease and lower rates of ART initiation among these patients. While many countries have adopted WHO guidelines, the impact of ART eligibility expansions on timely ART initiation has not been studied on a large scale. What did the researchers do and find? We examined the changes in timely ART initiation after national ART eligibility criteria were expanded to CD4 ≤ 350 and/or CD4 ≤ 500 in 22 countries, using data on 284,740 adult ART-naïve patients at 171 sites in the International Epidemiology Databases to Evaluate AIDS (IeDEA) network. Site-level cumulative incidence of ART initiation (CI-ART) within 6 months of enrollment increased by 4.3 percentage points after national ART eligibility expansion to CD4 ≤ 350 and by 15.9 percentage points after expansion to CD4 ≤ 500. At the individual level, increases were greatest among patients 16–24 years old at enrollment and those newly eligible for ART. No change or small improvements in CI-ART were also observed among patients already eligible for ART before eligibility expansion. At the site level, sites with the lowest initial levels of CI-ART experienced the greatest increases following guideline expansions. What do these findings mean? Overall, ART eligibility expansions were followed by appreciable improvements in timely ART initiation. Many clinics can support ART initiation among newly eligible patients with less advanced disease without negatively affecting ART initiation rates among those with more advanced disease. These findings illustrate the potential of ART eligibility expansion to improve the timeliness of ART initiation and patient outcomes along the care cascade globally, particularly for younger adults, in support of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets, thereby reducing morbidity, mortality, and onward HIV transmission.

Background Efavirenz (EFV) and boosted protease inhibitors (bPIs) are still the preferred options for firstline antiretroviral regimens (firstline ART) in Latin America and have comparable short-term efficacy. We assessed the long-term durability and outcomes of patients receiving EFV or bPIs as firstline ART in the Caribbean, Central and South America network for HIV epidemiology (CCASAnet). Methods We included ART-naïve, HIV-positive adults on EFV or bPIs as firstline ART in CCASAnet between 2000 and 2016. We investigated the time from starting until ending firstline ART according to changes of third component for any reason, including toxicity and treatment failure, death, and/or loss to follow-up. Use of a third-line regimen was a secondary outcome. Kaplan-Meier estimators of composite end points were generated. Crude cumulative incidence of events and adjusted hazard ratios (aHRs) were estimated accounting for competing risk events. Results We included 14 519 patients: 12 898 (89%) started EFV and 1621 (11%) bPIs. The adjusted median years on firstline ART were 4.6 (95% confidence interval [CI], 4.4–4.7) on EFV and 3.8 (95% CI, 3.8–4.0) on bPI (P < .001). Cumulative incidence of firstline ART ending at 10 years of follow-up was 32% (95% CI, 31–33) on EFV and 44% (95% CI, 39–48) on bPI (aHR, 0.88; 95% CI, 0.78–0.97). The cumulative incidence rates of third-line initiation in the bPI-based group were 6% (95% CI, 2.4–9.6) and 2% (95% CI, 1.4–2.2) among the EFV-based group (P < .01). Conclusions Durability of firstline ART was longer with EFV than with bPIs. EFV-based regimens may continue to be the preferred firstline regimen for our region in the near future due to their high efficacy, relatively low toxicity (especially at lower doses), existence of generic formulations, and affordability for national programs.

The growing elderly population of HIV-infected patients is leading to a significant epidemiological transition and HIV infection has been proposed as a premature and accelerated aging model rending the individual more susceptible to premature disability. However, the determinants of disability among this emergent population are still lacking. Therefore, the aim of this study is to determine the correlates of prevalent disability in adults ≥50 years with HIV infection. A cross-sectional study of 184 HIV-infected adults receiving ambulatory care in an HIV clinic of a tertiary care, university-affiliated hospital in Mexico City was conducted. Disability for instrumental (IADL) and basic activities of daily living (ADL) was established. Sociodemographic factors, clinical variables, current CD4(+) cell count, and HIV viral load (VL) were tested as potential determinants of disability. Multivariate logistic regression analyses were used to identify the correlates of both types of disability. The mean age was 59.3 years. All participants were receiving highly active antiretroviral therapy. Of participants 17.9% had disability for IADL and 26.1% for ADL. Multivariate logistic regression analyses indicated that being older; having a lower CD4(+) cell count, and having a detectable HIV VL were independently associated with both types of disability. In addition, educational level was also independently associated with ADL disability. Age, educational level, low CD4(+) cell count, and detectable HIV VL were independently associated with disability. Whether effective and timely antiretroviral therapy will reduce the risk of disability in HIV-infected elderly patients needs to be evaluated.

Background The week 48 primary analysis of the ENCORE1 trial established the virological non-inferiority and safety of efavirenz 400 mg compared with the standard 600 mg dose, combined with tenofovir and emtricitabine, as first-line HIV therapy. This 96-week follow-up of the trial assesses the durability of efficacy and safety of this treatment over 96 weeks. Methods ENCORE1 was a double-blind, placebo-controlled, non-inferiority trial done at 38 clinical sites in 13 countries. HIV-infected adult patients (≥16 years of age) with no previous antiretroviral therapy, a CD4 cell count of 50–500 cells per μL, and plasma HIV-1 viral load of at least 1000 copies per mL were randomly assigned (1:1) by an electronic case report form to receive fixed-dose daily tenofovir 300 mg and emtricitabine 200 mg plus efavirenz either 400 mg daily or 600 mg daily. Participants, physicians, and all other trial staff were masked to treatment assignment. Randomisation was stratified by HIV-1 viral load at baseline (≤ or >100 000 copies per mL). The primary endpoint was the difference in the proportions of patients in the two treatment groups with a plasma HIV-1 viral load below 200 copies per mL at week 96. Treatment groups were deemed to be non-inferior if the lower limit of the 95% CI for the difference in viral load was above −10% by modified intention-to-treat analysis. Non-inferiority was assessed in the modified intention-to-treat, per-protocol, and non-completer=failure (NC=F) populations. Adverse events and serious adverse events were summarised by treatment group. This study is registered with ClinicalTrials.gov, number NCT01011413. Findings Between Aug 24, 2011, and March 19, 2012, 636 eligible participants were enrolled and randomly assigned to the two treatment groups (324 to efavirenz 400 mg and 312 to efavirenz 600 mg). The intention-to-treat population who received at least one dose of study drug comprised 630 patients: 321 in the efavirenz 400 mg group and 309 in the efavirenz 600 mg group. 585 patients (93%; 299 in the efavirenz 400 mg group and 286 in the 600 mg group) completed 96 weeks of follow-up. At 96 weeks, 289 (90·0%) of 321 patients in the efavirenz 400 mg group and 280 (90·6%) of 309 in the efavirenz 600 mg group had a plasma HIV-1 viral load less than 200 copies per mL (difference −0·6, 95% CI −5·2 to 4·0; p=0·72), which suggests continued non-inferiority of the lower efavirenz dose. Non-inferiority was recorded for thresholds of less than 50 and less than 400 copies per mL, irrespective of baseline plasma viral load. Adverse events were reported by 291 (91%) of 321 patients in the efavirenz 400 mg group and by 285 (92%) of 309 in the 600 mg group (p=0·48). The proportions of patients reporting an adverse event that was definitely or probably related to efavirenz were 126 (39%) for efavirenz 400 mg and 148 (48%) for efavirenz 600 mg (p=0·03). The number of patients who reported serious adverse events did not differ between the groups (p=0·20). Interpretation Our findings confirm that efavirenz 400 mg is non-inferior to the standard dose of 600 mg in combination with tenofovir and emtricitabine as initial HIV therapy over 96 weeks. Fewer efavirenz-related adverse events were reported with the 400 mg efavirenz dose than with the 600 mg dose. These findings support the routine use of efavirenz 400 mg. The coadministration of rifampicin and efavirenz 400 mg needs further investigation. Funding Bill & Melinda Gates Foundation, and UNSW Australia

Background ARV treatment (ART) administered during acute HIV-infection presents several immunological benefits leading to a better CD4+ T-cell recovery and a diminished HIV reservoir. Methods Patients with acute HIV-infection, enrolled in the VIHIA cohort, had blood samples taken at diagnosis and at 2, 6 and 12 months after ART initiation. Flow-cytometry analysis was performed in fresh whole blood. Naïve-(Nv), central memory (CM), effector memory (EM) and terminally differentiated T-cells (TMRA), as well as activation markers were defined using CD3, CD4, CD8, CD45RA, CCR7, CD38, CD31 and HLA-DR markers. CD28 and CD57 were used to identify immunosenescent cells. Fox-P3, CD 25, CD127 and CD45RA were used to identify Regulatory T cells (Treg) and their subsets. To assess changes over time, Wilcoxon-matched-pairs signed rank test was used for each value between baseline and months 2 and 12 independently. Results Four patients were diagnosed at Fiebig stage II; 5 patients at Fiebig stage III, 24 patients at stage IV and 5 patients in stage V. All patients received treatment within the first 24 hours of HIV diagnosis. Only 13 patients had flow-cytometry data at baseline and 1 year of follow-up. All subjects were MSM with a mean age of 32 y.o. Mean CD4+ T-cell count was 439 cells/μL and mean viral load was 1.2 million copies/mL (23,379–10 × 106 copies/mL) at baseline. The change in T-cell differentiation patterns at 0 and 12 months is shown in Figure 1. Activation markers decreased in all studied subsets at 2 months and furthermore at 12 months. Total T-regs increased from 5.1% to 7.8% at 1 year of follow-up (Figure 2). Immunosenescence markers increased steadily throughout the study in all T-cell subsets, being statistically significant in the total T-cell CD8 population at 12 months of follow-up (Figure 3) unrelated to Fiebig stage. Conclusion It has been hypothesized that early ART decreases T-cell immunosenescence; however, in our cohort despite treatment during acute HIV, we observed that at 1 year follow-up immunosenescence markers increased despite a decrease in immune activation and a recovery of T-cell subsets. Disclosures All authors: No reported disclosures.

OBJECTIVE To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with