Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial.

Background: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/µL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS.

Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection.

We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.

Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial.

BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.

The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America.

INTRODUCTION: Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND ANALYSIS: This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA's global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial.

Objective: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). Design: Open label, randomised clinical trial. Setting: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. Participants: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression. Interventions: Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40. Main outcome measures: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. Results: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). Conclusions: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. Trial registration: ClinicalTrials.gov NCT04345991.

Updated mortality and causes of death in 2020-2021 in people with HIV: a multicenter study in France.

OBJECTIVE: The aim of this study was to assess updated mortality and causes of death in people with HIV (PWH) in France. DESIGN AND METHODS: We analyzed all deaths in PWH followed up between January 1, 2020, and December 31, 2021, in 11 hospitals in the Paris region. We described the characteristics and causes of death among deceased PWH, and evaluated the incidence of mortality and associated risk factors using a multivariate logistic regression. RESULTS: Of the 12 942 patients followed in 2020--2021, 202 deaths occurred. Mean annual incidence of death [95% confidence interval (95% CI)] was 7.8 per 1000 PWH (6.3-9.5). Forty-seven patients (23%) died from non-AIDS nonviral hepatitis (NANH)-related malignancies, 38 (19%) from non-AIDS infections (including 21 cases of COVID-19), 20 (10%) from AIDS, 19 (9%) from cardiovascular diseases (CVD), 17 (8.4%) from other causes, six (3%) from liver diseases, and five (2.5%) from suicides/violent deaths. The cause of death was unknown in 50 (24.7%) patients. Risks factors for death were age [adjusted odds ratio (aOR) 1.93; 1.66-2.25 by additional decade), AIDS history (2.23; 1.61-3.09), low CD4 + cell count (1.95; 1.36-2.78 for 200-500 cells/µl and 5.76; 3.65-9.08 for ≤200 versus > 500 cells/µl), and viral load more than 50 copies/ml (2.03; 1.33-3.08), both at last visit. CONCLUSION: NANH malignancies remained in 2020-2021 the first cause of death. COVID-19 accounted for more than half of the mortality related to non-AIDS infections over the period. Aging, AIDS history, and a poorer viro-immunological control were associated with death.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

SARS-CoV-2 N-Antigen Quantification in Respiratory Tract, Plasma and Urine: Kinetics and Association with RT-qPCR Results.

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, we tested 26 patients for viral RNA and N-antigen in respiratory samples, plasma and urine. This allowed us to compare the kinetics between the three compartments and to compare RNA and antigen concentrations in each. Our results showed the presence of N-antigen in respiratory (15/15, 100%), plasma (26/59, 44%) and urine (14/54, 28.9%) samples, whereas RNA was only detected in respiratory (15/15, 100%) and plasma (12/60, 20%) samples. We detected N-antigen in urine and plasma samples until the day 9 and day 13 post-inclusion, respectively. The antigen concentration was found to correlate with RNA levels in respiratory (p < 0.001) and plasma samples (p < 0.001). Finally, urinary antigen levels correlated with plasma levels (p < 0.001). Urine N-antigen detection could be part of the strategy for the late diagnosis and prognostic evaluation of COVID-19, given the ease and painlessness of sampling and the duration of antigen excretion in this biological compartment.

Virologic response to antiretroviral therapy in people with HIV and tuberculosis in high tuberculosis burden countries.

OBJECTIVE: We sought to compare virologic outcomes on antiretroviral therapy (ART) between people with HIV (PWH) also treated for tuberculosis in the different countries who participated to two randomized trials. DESIGN: Pooled analysis of two randomized clinical trials. METHODS: In the phase II Reflate TB and phase III Reflate TB2 trials conducted in Brazil, Côte d'Ivoire, Mozambique and Vietnam, ART-naïve PWH treated for tuberculosis were randomized to receive raltegravir or efavirenz. We assessed country differences in baseline characteristic using Wilcoxon tests and chi-square, or Fisher's exact test. We used logistic regression to analyze determinants of virologic success, defined as week-48 plasma HIV-1 RNA <50 copies/ml. RESULTS: Of 550 participants (140 from Brazil, 170 from Côte d'Ivoire, 129 from Mozambique and 111 from Vietnam) with median baseline HIV-1 RNA of 5.4 log 10  copies/ml, 362 (65.8%) achieved virologic success at week 48. Virologic success rates were: 105/140 (75.0%) in Brazil, 99/170 (58.2%) in Côte d'Ivoire, 84/129 (65.1%) in Mozambique and 74/111 (66.7%) in Vietnam ( P  = 0.0233). Baseline HIV-1 RNA, but not the country, was independently associated with virologic success: baseline HIV-1 RNA ≥500 000 copies/ml (reference), HIV RNA <100 000 copies/ml odds ratio 3.12 [95% confidence interval (CI) 1.94; 5.01] and HIV-1 RNA 100 000-499 999 copies/ml odds ratio: 1.80 (95% CI 1.19; 2.73). Overall, 177/277 (63.9%) patients treated with raltegravir and 185/273 (67.9%) patients treated with efavirenz had a plasma HIV-1 RNA <50 copies/ml at week 48. CONCLUSIONS: Virologic response to antiretroviral therapy in PWH with TB varied across countries but was mainly driven by levels of pretreatment HIV-1 RNA.

Atypical presentation of Mycobacterium xenopi pulmonary infection in a kidney transplant recipient: A case report and literature review.

Background: Mycobacterium xenopi is one of the most common pathogens responsible for non-tuberculosis mycobacteria (NTM) pulmonary diseases, which are associated with poor prognosis in immunocompromised patients. Case presentation: We report the unusual case of a 44-year-old kidney transplant recipient with multiple pulmonary nodules revealing M. xenopi pulmonary disease with atypical presentation. A three drug-regimen containing moxifloxacin, ethambutol and azithromycin was prescribed, with careful monitoring of the immunosuppressive therapy. The outcome was favorable. Discussion and conclusion: Although infrequent in kidney transplant recipients, NTM can cause pulmonary infection several years after transplantation. Treatment of M. xenopi infection relies on a multidrug regimen with at least 3 antimycobacterial drugs. Drug-drug interactions between immunosuppressive treatments and rifamycins require careful dose adjustment and monitoring to avoid graft rejection.

Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study.

OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.

Influence of UGT1A1 and SLC22A6 polymorphisms on the population pharmacokinetics and pharmacodynamics of raltegravir in HIV-infected adults: a NEAT001/ANRS143 sub-study.

Using concentration-time data from the NEAT001/ARNS143 study (single sample at week 4 and 24), we determined raltegravir pharmacokinetic parameters using nonlinear mixed effects modelling (NONMEM v.7.3; 602 samples from 349 patients) and investigated the influence of demographics and SNPs (SLC22A6 and UGT1A1) on raltegravir pharmacokinetics and pharmacodynamics. Demographics and SNPs did not influence raltegravir pharmacokinetics and no significant pharmacokinetic/pharmacodynamic relationships were observed. At week 96, UGT1A1*28/*28 was associated with lower virological failure (p = 0.012), even after adjusting for baseline CD4 count (p = 0.048), but not when adjusted for baseline HIV-1 viral load (p = 0.082) or both (p = 0.089). This is the first study to our knowledge to assess the influence of SNPs on raltegravir pharmacodynamics. The lack of a pharmacokinetic/pharmacodynamic relationship is potentially an artefact of raltegravir's characteristic high inter and intra-patient variability and also suggesting single time point sampling schedules are inadequate to thoroughly assess the influence of SNPs on raltegravir pharmacokinetics.

Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis.

Background: In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. Methods: In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Results: Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16-2.72; P = .0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33-3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56-3.62; P < .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71-.92; P = .0018). Conclusions: In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence.

Metagenomic next-generation sequencing restores the diagnosis of a rare infectious complication of B cell depletion.

A 45-year-old female patient receiving rituximab for B cell non-Hodgkin follicular lymphoma presented unexplained recurrent fever, abdominal discomfort, and pollakiuria. We performed shotgun metagenomic sequencing from peri-kidney collection that identified a co-infection with Mycoplasma hominis and Ureaplasma urealyticum. The patient recovered with sequelae after appropriate antibiotic treatment was given.

Brief Report: Efficacy and Safety of Efavirenz, Raltegravir, and Dolutegravir in HIV-1/TB Coinfection. A Multicenter Retrospective Cohort Study in France.

BACKGROUND: There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) coinfected patients. METHODS: We conducted a 10-year retrospective study in 4 centers in France. We included all HIV-1/tuberculosis coinfected patients starting antiretroviral therapy with a rifampicin-based regimen, with a plasma HIV RNA level (VL) > 1000 copies/mL. The primary endpoint was the proportion of patients with virological success that is, with VL <50 copies/mL at W48 using an Intention-To-Treat analysis, using last-observation-carried-forward to impute missing data. We also assessed antiretroviral therapy safety, analyzing treatment discontinuation for adverse events. RESULTS: Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and 2 NRTIs) and 59 (50.4%) with efavirenz (and 2 NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an Intention-To-Treat analysis ( P = 0.68). Emergence of drug resistance in patients with virological failure, defined as a VL >50 copies/mL, was observed in 3 patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively ( P = 0.67). CONCLUSIONS: In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB coinfected patients.

Remdesivir in combination with dexamethasone for patients hospitalized with COVID-19: A retrospective multicenter study.

BACKGROUND: Dexamethasone is standard of care for the treatment of patients with COVID-19 requiring oxygen. The objective is to assess the clinical benefit of adding remdesivir to dexamethasone. PATIENTS AND METHODS: A retrospective cohort study of hospitalized patients with COVID-19 pneumonia requesting low-flow oxygen who received dexamethasone. Patients admitted to infectious diseases wards also received remdesivir. Primary outcome was duration of hospitalization after oxygen initiation. Secondary outcomes were in-hospital death, and death and/or transfer to the intensive care unit. To handle potential confounding by indication bias, outcome comparison was performed on propensity score-matched populations. Propensity score was estimated by a multivariable logistic model including prognostic covariates; then 1:1 matching was performed without replacement, using the nearest neighbor algorithm with a caliper of 0.10 fold the standard deviation of the propensity score as the maximal distance. Balance after matching was checked on standardized mean differences. RESULTS: From August 15th 2020, to February 28th, 2021, 325 patients were included, 101 of whom received remdesivir. At admission median time from symptoms onset was 7 days, median age: 68 years, male sex; 61%, >1 comorbidity: 58.5%. Overall 180 patients matched on propensity score were analyzed, 90 each received remdesivir plus dexamethasone or dexamethasone alone. Median duration of hospitalization was 9 (IQR: 7-13) and 9 (IQR: 5-18) days with and without remdesivir, respectively (p = 0.37). In-hospital death rates and rates of transfer to the intensive care unit or death were 8.9 and 17.8% (HR: 0.46, 95% CI: 0.21-1.02, p = 0.06) and 20.0 and 35.6% with and without remdesivir, respectively (HR: 0.45, 95% CI: 0.23-0.89, p = 0.015). CONCLUSION: In hospitalized patients with COVID-19 pneumonia receiving low-flow oxygen and dexamethasone, the addition of remdesivir was not associated with shorter hospitalization or lower in-hospital mortality but may have reduced the combined outcome of death and transfer to the intensive care unit.

Profiles and outcomes in patients with COVID-19 admitted to wards of a French oncohematological hospital: A clustering approach.

OBJECTIVES: Although some prognostic factors for COVID-19 were consistently identified across the studies, differences were found for other factors that could be due to the characteristics of the study populations and the variables incorporated into the statistical model. We aimed to a priori identify specific patient profiles and then assess their association with the outcomes in COVID-19 patients with respiratory symptoms admitted specifically to hospital wards. METHODS: We conducted a retrospective single-center study from February 2020 to April 2020. A non-supervised cluster analysis was first used to detect patient profiles based on characteristics at admission of 220 consecutive patients admitted to our institution. Then, we assessed the prognostic value using Cox regression analyses to predict survival. RESULTS: Three clusters were identified, with 47 patients in cluster 1, 87 in cluster 2, and 86 in cluster 3; the presentation of the patients differed among the clusters. Cluster 1 mostly included sexagenarian patients with active malignancies who were admitted early after the onset of COVID-19. Cluster 2 included the oldest patients, who were generally overweight and had hypertension and renal insufficiency, while cluster 3 included the youngest patients, who had gastrointestinal symptoms and delayed admission. Sixty-day survival rates were 74.3%, 50.6% and 96.5% in clusters 1, 2, and 3, respectively. This was confirmed by the multivariable Cox analyses that showed the prognostic value of these patterns. CONCLUSION: The cluster approach seems appropriate and pragmatic for the early identification of patient profiles that could help physicians segregate patients according to their prognosis.

Ultrasensitive Detection of p24 in Plasma Samples from People with Primary and Chronic HIV-1 Infection.

HIV-1 Gag p24 has long been identified as an informative biomarker of HIV replication, disease progression, and therapeutic efficacy, but the lower sensitivity of immunoassays in comparison to molecular tests and the interference with antibodies in chronic HIV infection limit its application for clinical monitoring. The development of ultrasensitive protein detection technologies may help in overcoming these limitations. Here, we evaluated whether immune complex dissociation combined with ultrasensitive digital enzyme-linked immunosorbent assay (ELISA) single-molecule array (Simoa) technology could be used to quantify p24 in plasma samples from people with HIV-1 infection. We found that, among different immune complex dissociation methods, only acid-mediated dissociation was compatible with ultrasensitive p24 quantification by digital ELISA, strongly enhancing p24 detection at different stages of HIV-1 infection. We show that ultrasensitive p24 levels correlated positively with plasma HIV RNA and HIV DNA and negatively with CD4-positive (CD4+) T cells in the samples from people with primary and chronic HIV-1 infection. In addition, p24 levels also correlated with plasma D-dimers and interferon alpha (IFN-α) levels. p24 levels sharply decreased to undetectable levels after initiation of combined antiretroviral treatment (cART). However, we identified a group of people who, 48 weeks after cART initiation, had detectable p24 levels despite most having undetectable viral loads. These people had different virological and immunological baseline characteristics compared with people who had undetectable p24 after cART. These results demonstrate that ultrasensitive p24 analysis provides an efficient and robust means to monitor p24 antigen in plasma samples from people with HIV-1 infection, including during antiretroviral treatment, and may provide complementary information to other commonly used biomarkers. IMPORTANCE The introduction of combined antiretroviral treatment has transformed HIV-1 infection into a manageable condition. In this context, there is a need for additional biomarkers to monitor HIV-1 residual disease or the outcome of new interventions, such as in the case of HIV cure strategies. The p24 antigen has a long half-life outside viral particles, and it is, therefore, a very promising marker to monitor episodes of viral replication or transient activation of the viral reservoir. However, the formation of immune complexes with anti-p24 antibodies makes its quantification difficult beyond acute HIV-1 infection. We show here that, upon immune complex dissociation, new technologies allow the ultrasensitive p24 quantification in plasma samples throughout HIV-1 infection at levels close to those of viral RNA and DNA determinations. Our results further indicate that ultrasensitive p24 quantification may have added value when used in combination with other classic clinical biomarkers.