Scientific News

Background: The WHO recommends an optimal treatment duration of 2 months for new treatment regimens for rifampicin-sensitive tuberculosis. The objective was to evaluate the efficacy and safety of 8-week treatment regimens assessed as part of the TRUNCATE management strategy in the TRUNCATE-TB trial.

Methods: The TRUNCATE-TB study was a randomized, open-label, multi-arm, multi-stage controlled trial in which participants aged 18 to 65 years with rifampicin-sensitive pulmonary tuberculosis were randomized to receive either a 24-week standard treatment (rifampin, isoniazid, pyrazinamide, and ethambutol), or the TRUNCATE management strategy, consisting of an initial 8-week course of treatment, followed by post-treatment monitoring and retreatment if necessary. The four 8-week treatment regimens consisted of five drugs, modified from the standard treatment: high-dose rifampin and linezolid, or high- dose rifampin and clofazimine, or bedaquiline and linezolid, all administered with isoniazid, pyrazinamide, and ethambutol; and rifapentine, linezolid, and levofloxacin, administered with isoniazid and pyrazinamide. Here, we present the efficacy (proportion of adverse outcomes and difference compared with standard treatment, assessed using Bayesian methods) and safety of the 8-week treatment regimens, evaluated in the intent-to-treat population. This predefined exploratory analysis is distinct from the previously published 96-week results regarding the strategy under which the treatment regimens were deployed.

Results: 675 participants (including 674 in the intent-to-treat population) were enrolled in the study and randomized to the standard treatment group or to one of the four 8-week treatment groups. Two 8-week treatment regimens reached their full enrollment. An adverse event (primarily relapse) occurred in seven (4%) of the 181 participants in the standard treatment group; in 46 (25%) of the 184 participants in the high-dose rifampin and linezolid group (adjusted difference: 21.0%, 95% Bayesian credibility interval [BCI]: 14.3–28.1); and in 26 (14%) of the 189 participants in the bedaquiline and linezolid group (adjusted difference: 9.3% [4.3–14.9]). Grade 3–4 adverse events occurred in 24 (14%) of the 181 participants receiving standard therapy, in 20 (11%) of the 184 receiving rifampin-linezolid, and in 22 (12%) of the 189 receiving bedaquiline-linezolid.

Conclusion: Efficacy was lower with the 8-week treatment regimens, although the difference compared with standard treatment varied by regimen. Even the most effective 8-week regimen (bedaquiline-linezolid) should only be used as part of a management strategy that includes post-treatment follow-up and retreatment if necessary.

Background: The DTG/3TC dual-therapy regimen demonstrated non-inferiority compared with triple therapy in the GEMINI trials. Although the population with a CD4 count ≤ 200 cells/mm³ had a lower response rate, this was not associated with virologic failure. This trial evaluated the efficacy of DTG/3TC in antiretroviral-naive patients with HIV infection and a CD4 count ≤ 200/mm³.

Methods: DOLCE is a multicenter, randomized, open-label trial evaluating the efficacy of DTG/3TC at week 48 in treatment-naive people living with HIV (PLHIV) with a CD4 count ≤ 200/mm³. Participants were randomized in a 2:1 ratio to receive either DTG/3TC as a single tablet or DTG combined with TDF/XTC: FTC or 3TC. The primary endpoint was the proportion of participants with a plasma viral load < 50 copies/mL at week 48 (exposed population analysis based on the intention-to-treat principle, in accordance with FDA recommendations).

Results: Baseline characteristics were similar in both groups. In the DT group, the median CD4 lymphocyte count was 109 cells/mm³ (interquartile range [IQR]: 49–177) and the median plasma viral load was 180,000 copies/mL (IQR: 53,309 –468,691); 45.4% of patients had a CD4 count < 100 cells/mm³, 61.4% had a viral load > 100,000 copies/mL, and 31.4% were at stage C. At week 48, virologic suppression (viral load < 50 copies/mL) was achieved in 82.2% of patients in the DT group (125/152), and the CD4 count increased by 200/mm³. The per-protocol analysis showed a response rate of 91.9%. Serious adverse events (n = 17) were reported in 15 of the 152 participants (11.1%).

Conclusions: Dolutegravir/3TC demonstrated high efficacy in a population with low CD4 counts and high viral loads

Background: The impact of the pharmacokinetic variability of cabotegravir (CAB) and long-acting (LA) injectable rilpivirine (RPV) on virologic outcomes remains controversial. This study aimed to characterize the variability of residual concentrations (Crés) of CAB and RPV and to identify predictors of suboptimal exposure and virologic failure in a large real-world cohort.

Methods: We conducted a multicenter observational study among people living with HIV-1 (PLHIV) who initiated maintenance therapy with LA-CAB/RPV from January through December 2022, in whom residual plasma concentrations of CAB and RPV were determined as part of pharmacokinetic monitoring.

Results: A total of 1,674 CAB Cmax measurements and 1,687 RPV Cmax measurements were collected from 736 HIV-1-positive individuals. Significant interindividual variability in concentrations was observed. At months 1 and 3, 20–30% of PLWHIV had C_(res) < 1,120 ng/mL for CAB and < 32 ng/mL for RPV. Predictors of lower C_(res) were a BMI ≥ 30 kg/m² and female sex at month 1, and male sex alone at steady state. After a median follow-up of 12 months (interquartile range: 9–16 months), virologic failure occurred in 2.5% of PLWHIV. At months 6 and 12, virologic failure was significantly associated with the presence of at least 2 risk factors (obesity, suboptimal CRF) (odds ratio 4.6, P = 0.047; OR, 5.15, P = 0.014) and CD4 nadir (OR, 0.56, P = 0.008; OR, 0.5, P = 0.001).

Conclusions: This large real-world study confirms significant variability in CAB and RPV exposure, with BMI and sex being key predictors of lower Crés. Suboptimal CAB and RPV exposure, particularly among obese individuals, increases the risk of virologic failure during the first year of treatment, underscoring the value of pharmacokinetic monitoring in clinical practice.

Background: Uncertainty regarding the role of neurosurgery in the treatment of brain abscesses is reflected in surveys and observational studies.

Methods: A population-based national cohort study of all adults (≥ 18 years) diagnosed with a brain abscess in Denmark between 2007 and 2023. Inverse probability weighting was applied to balance covariates according to neurosurgical treatment strategy. Outcomes included the risks of mortality, rupture, and poor outcome (Glasgow Coma Scale 1–4) six months after hospital discharge and were assessed using Poisson and modified Cox regression with 95% confidence intervals (CI).

Results: The cohort comprised 558 patients (median age 59 years [interquartile range 49–69], 66% men). A non-surgical strategy was assigned to 234/558 (42%) and neurosurgery to 324/558 (58%). Concomitant meningitis, abscess diameter, and deep abscess location were included in the doubly robust estimates. Analyses of treatment strategy showed that a non-surgical approach was associated with adjusted relative risks of 2.47 (95% CI: 1.50–4.04) for mortality, 2.25 (95% CI: 1.26–4.01) for rupture, and 1.24 (95% CI: 0.95–1.61) for adverse outcomes compared with neurosurgery. In addition, 85 of 234 (36%) patients assigned to the non-surgical strategy required subsequent neurosurgery. Compared with neurosurgery at any time, continued non-surgical treatment was associated with adjusted risk ratios of 1.53 (95% CI: 0.84–2.76) for mortality, 2.00 (95% CI: 1.17–3.42) for rupture, and 1.62 (95% CI: 1.12–2.34) for adverse outcomes.

Conclusions: The non-surgical strategy was associated with a twofold increased risk of mortality and rupture, and one-third of patients required subsequent neurosurgery. These results support the recommendations in favor of neurosurgical drainage of brain abscesses.

Bacteremia is a common, potentially life-threatening complication in hematologic patients with febrile neutropenia (FN). However, blood culture (BC) detects a microorganism in only 20–30% of patients with FN. Our objective was to evaluate the diagnostic performance of next-generation metagenomic sequencing (mNGS) as a first-line diagnostic method for bacteremia. This study was conducted prospectively at four Chinese hematology centers. In patients aged 15 years and older with hematologic diseases, peripheral blood samples were collected from each patient to perform both BC and mNGS simultaneously upon the onset of NF. The clinical team and the mNGS analysis team conducted the study as a double-blind trial, and the clinical diagnosis was established by a separate panel of experts consisting of four specialists. The primary endpoint of this study was the diagnostic performance of mNGS. Three hundred episodes of NF were recorded, including 62 confirmed bacteremias, 61 probable bacteremias, 116 infections other than bacteremias, 55 non-infectious episodes, and 6 of undetermined cause. Among the 62 cases of confirmed bacteremia, mNGS identified the causative pathogens in 59 cases (95.2%). Concomitant blood culture initially detected pathogens in 59 cases, and three additional pathogens consistent with mNGS results were subsequently identified during repeat blood cultures. The sensitivity, specificity, positive predictive value, and negative predictive value of mNGS were 95.2%, 94.6%, 95.2%, and 94.6%, respectively. The diagnostic turnaround time for mNGS was significantly shorter than that for blood culture (39.7 ± 15.0 vs. 119.8 ± 31.9 h, p < 0.0001). The results suggest that the mNGS approach offers excellent diagnostic performance for the first-line diagnosis of bacteremia in patients with NF, enabling early diagnosis and improved patient care.

Background: Encephalitis is characterized by inflammation of the brain parenchyma of infectious or autoimmune origin. Recent data on differences between immunocompromised and non-immunocompromised patients with encephalitis are limited.

Methods: This retrospective study, conducted at two major hospitals, compared the clinical characteristics and outcomes of immunocompromised and immunocompetent patients with encephalitis from all causes.

Results: Of the 657 patients, 151 (23%) were immunocompromised. Immunocompromised patients were more likely to have an infectious etiology, comorbidities, an inflammatory CSF profile, abnormal neuroimaging findings, a poorer clinical outcome as assessed by the Glasgow Outcome Scale (GODS) at discharge, and in-hospital mortality (all p < 0.05). The most frequently identified etiologies in immunocompromised patients were HSV and VZV. HSV accounted for similar proportions in the immunocompromised (18%) and immunocompetent (14%) groups, although it was more frequently associated with CSF neutrophilia in the immunocompromised group (p = 0.001). More than 10% of immunocompromised patients with encephalitis had autoimmune causes, two-thirds of which were associated with an immune checkpoint inhibitor. Factors associated with a poor Glasgow Outcome Scale (GODS) score at hospital discharge differed between the two populations; outcomes were poorer in cases of infectious etiologies associated with immunocompromised status and in cases of autoimmune etiologies associated with immunocompetent status.

Conclusions: Compared with immunocompetent patients, immunocompromised patients with encephalitis have different causes, atypical clinical presentations, higher in-hospital mortality, and distinct factors associated with a poor prognosis. Although HSV and opportunistic infections cause encephalitis in immunocompromised patients, the diagnosis of autoimmune encephalitis should also be considered and may be associated with an immune checkpoint inhibitor.

Introduction: Due to the rise in NNRTI resistance, several million people living with HIV have switched to a DTG-based regimen. Investigating the potential emergence of DTG resistance is essential. The objective of this study was to predict the evolution of DTG resistance over time in South Africa.

Method: This modeling study used the MARISA (Modeling Antiretroviral Drug Resistance in South Africa) model, a deterministic compartmental model capable of simulating the HIV-1 epidemic in South Africa between 2005 and 2035, based on the literature and international collaboration with epidemiological databases for AIDS assessment (IeDEA). My main modeling parameters for the evolution of DTG resistance were the rates of acquisition of DTG resistance mutations, the reversion of DTG resistance mutations, the effect of NRTIs on the acquisition of DTG resistance, the effect of DTG resistance on treatment efficacy, the probability of transmission of DTG resistance mutations compared to that of wild-type strains, and the proportion of individuals experiencing virologic failure on DTG with detectable drug concentrations. The model allowed for the estimation of the transmission of DTG resistance and acquired DTG resistance.

Results: The model estimated a substantial increase in the number of individuals on ARV therapy with DTG following its introduction in 2020, rising from 0 to approximately 7 million by 2035. The estimated proportion of PLWHIV with virologic suppression (viral load < 1,000 c/ml) is 93%. The estimated rate of acquired resistance to DTG following treatment failure with DTG is rising rapidly, reaching 18.5% (12.5–25.4%) in 2023 and 41.7% (29–54%) in 2035. The estimated rate of DTG resistance transmission is projected to rise from 0.1% in 2023 to 5% (1.9–11.9%) in 2035. Strategies to prevent resistance, such as a rapid switch to protease inhibitor (PI) therapy, could effectively reduce the increase in acquired DTG resistance and slow the rise in transmitted resistance.

Conclusion: Although antiretroviral (ARV) treatment with DTG is associated with a very high rate of virologic suppression, acquired and transmitted resistance to DTG are likely to increase. This increase is likely to be more pronounced in settings where there is limited capacity to monitor viral load, perform genotyping, and switch to other ARV regimen options.

Introduction: In the REPRIEVE trial, pitavastatin reduced the rate of major cardiovascular events (MCE) among people living with HIV (PLHIV) with low or moderate cardiovascular risk. This study investigated the association between prior and ongoing antiretroviral therapy (ART) use during the trial and the occurrence of MCE.

Methods: This longitudinal analysis was a pre-specified secondary endpoint. REPRIEVE was a randomized, double-blind trial (pitavastatin or placebo) in people living with HIV aged 40 to 75 years who were on ARVs, had a CD4 count > 100/mm³, and were at low to moderate cardiovascular risk. Data on ARV use since treatment initiation were collected. The primary outcome was the time to the first occurrence of CVD. The relative risk of CVD according to ARV exposure was estimated using Cox proportional hazards models. The effect of no prior exposure, prior exposure, and current exposure at trial entry was compared using models that were both unadjusted and adjusted for risk factors and antiretroviral therapy at the start of the study.

Results: The 7,769 participants included were predominantly men (68.9%), 41.3% were Black, 34.8% were White, had a median age of 50.0 years, a median LDL cholesterol level of 106 mg/dl, a median 0-year cardiovascular risk score of 4.5%, a median CD4 count of 621/mm³, and 97.8% had a viral load < 400 copies/mL. The median duration of antiretroviral therapy (ART) at trial enrollment was 9.6 years, with prior exposure to ABC in 21.9%, TDF in 86%, ZDV or d4T in 49.3%, and PI in 47.4%; current exposure to ABC was reported in 12.6%, to TDF in 61%, to a thymidine analog in 9.7%, and to PI in 25.6%. In the adjusted analysis, prior or current exposure to ABC was associated with a higher risk of MCE than among participants who had never been exposed (HR [95% CI] of 1.62 [1.14–2.30] and 1.41 [1.01–1.96], respectively). No other associations between past or current exposure to ARVs and MCD were identified.

Conclusion: Previous or current exposure to ABC increases the risk of CVD in PLWHIV with low to moderate cardiovascular risk, suggesting that ABC should be avoided and that previous exposure should be taken into account when assessing the risk of CVD in this population.

Introduction: The health of children who are uninfected but exposed to HIV requires long-term assessment, particularly with regard to neurological and cognitive development. Numerous confounding factors have hindered this assessment, and published data are contradictory.

Method: Data from the National Health Insurance Data System in France between 2012 and 2022. A case-control cohort of all children born during this period, including those born to HIV-positive mothers and exposed to ARVs in utero. Outcome measures: neurodevelopmental disorders (ICD-10), use of specialized care that may indirectly correspond to neurodevelopmental disorders. Incidence assessed using the Cox model.

Results: Among 6,667,363 singleton children, 9,035 were born to HIV-positive mothers, all of whom were exposed to ARVs in utero. The children were followed for a mean duration of 5.5 years. The overall incidence of neurodevelopmental disorders was higher among exposed children than in the general population, even after matching on five sociodemographic criteria and gestational age (hazard ratio = 1.24, 95% CI: 1.04–1.47). It was not possible to distinguish the respective roles of maternal infection and ARV treatment, as all children were exposed to ARVs. However, among those exposed to TDF/FTC, rDRV was associated with a higher incidence of neurodevelopmental disorders and specialized consultations than other rPIs (log-rank p < 0.001).

Conclusion: Children exposed to HIV and ARVs in utero have a higher risk of neurodevelopmental disorders, which have multifactorial causes.

Background: The role of NRTIs in cardiovascular risk among people living with HIV is controversial.

Objectives: To evaluate the association between NNRTs and the progression of subclinical atherosclerosis as measured by carotid intima-media thickness.

Method: A prospective study in virologically controlled PLWHIV receiving treatment with NNRTs or NNTIs. Carotid intima-media thickness was measured at Day 0, Week 48, and Week 96. The progression of carotid intima-media thickness (an increase of ≥ 10% and/or new carotid plaque ) was analyzed as a continuous or discrete variable. Adjustments were made using Cox regression and mixed-effects linear models, and propensity score matching was performed.

Results: Among the 190 participants (INI: 56.3%, INNTI: 67.4%, INI + INNTI: 23.7%), 173 were followed up to S96. The median change in carotid intima- media thickness at S96 was 0.029 (IQR –0.041 to 0.124) mm, with 45% of participants showing an increase of ≥10% and 28.4% developing a new carotid plaque. The adjusted Cox regression model found no difference between the two groups — INI and INNTI— regarding 2-year progression of carotid intima- media thickness, whether participants receiving both INI and INNTI were included or excluded. Similar results were obtained when analyzing the change in carotid intima-media thickness as a continuous variable in a mixed-effects linear model. Propensity score matching did not reveal a significant difference in the change in carotid intima-media thickness between the two groups (0.049 [−0.031 to 9.103] mm for the INI group vs. 0.047 (−0.023 to 0.115) in the INNTI group, p = 0.647). The progression of carotid intima-media thickness was associated with traditional cardiovascular risk factors.

Conclusion: Treatment with INIs is not associated with an increase in the progression of subclinical atherosclerosis compared with treatment with NNRTIs.

Introduction: Data are limited regarding the potential reduction in post-COVID conditions through vaccination among patients who had non-severe COVID- 19 that did not require hospitalization. This study determined whether vaccination protected against post-COVID conditions in individuals who had a moderate form of infection during the Delta and Omicron waves.

Method: A case-control study nested within the HEROES-RECOVER cohort. Participants aged ≥ 18 years with a confirmed SARS-CoV-2 infection between June 2021 and September 2022 were assessed for post-COVID conditions, defined as persistent symptoms at least 4 weeks after the initial infection. For both cases and controls (no symptoms), data were self-reported. Exposure was defined as mRNA vaccination (2 or 3 doses of a monovalent vaccine). The risks of post-COVID conditions among vaccinated and unvaccinated individuals were compared using logistic regression.

Results: Among the 936 participants, 23.6% reported post-COVID conditions, and 83.2% were vaccinated. Participants who received 3 doses of the vaccine had a lower risk of gastrointestinal, neurological, or other symptoms than those who were unvaccinated (ORa; 95% CI: 0.37; 0.16 to 0.85, 0.56; 0.32 to 0.97, 0.48; 0.25 to 0.91)

Conclusions: COVID-19 vaccination protects against the onset of post-COVID conditions in individuals who experienced a moderate infection during the Delta or Omicron waves and is an important tool for preventing post-COVID conditions.

Introduction: People living with HIV (PLHIV) have a higher risk of myocardial infarction than the general population. However, the underlying mechanisms linking HIV infection to this increased risk remain unclear. The objective of this study was to compare the prevalence and characteristics of subclinical coronary atherosclerosis in PLHIV compared to controls.

Methods: Participants were recruited from the Copenhagen Study of Comorbidities in HIV Infection and the Copenhagen General Population Study. The presence of any subclinical coronary lesion or obstructive lesion (stenosis ≥ 50%) was assessed using coronary CT angiography. Analyses were adjusted for cardiovascular risk factors, including age, sex, hypertension, dyslipidemia, current smoking, overweight or obesity, and diabetes.

Results: The study included 519 PLWHIV and 1,114 sex-matched controls. The median age was 52 years, and 89% were men. Cardiovascular risk assessed by SCORE2 was similar among PLWHIV and controls (low to moderate risk: 43% and 42%, respectively; high risk: 50% and 52%, respectively). PLWHIV had a significantly higher prevalence of any type of subclinical coronary lesion (54% vs. 42%, p < 0.001) or obstructive coronary lesion (16% vs. 8%, p < 0.001). After adjusting for cardiovascular risk factors, HIV infection was associated with an odds ratio of 1.98 (95% CI: 1.52 to 2.58) for any type of subclinical coronary lesion and 3.21 (2.00 to 5.17) for obstructive lesions.

Conclusion: HIV infection is independently associated with a threefold increased risk of subclinical obstructive coronary artery disease. These findings provide a possible explanation for the increased risk of myocardial infarction among people living with HIV.

Introduction: Temocillin is increasingly used as an alternative to carbapenems. However, there is no consensus on optimal dosing strategies, and efficacy data for systemic infections are limited.

Objective: To compare dosing strategies using a PK/PD model, simulation data based on plasma exposure, and in vitro bactericidal activity data.

Method: The effects of temocillin on 4 strains of Escherichia coli were evaluated using bactericidal curves and hollow-fiber infection models, in which free plasma concentrations following administration of temocillin via intermittent or continuous infusion at doses of 4 and 6 g/day were measured over a 72- hour period. A PK/PD model was developed to describe bactericidal activity and was coupled with a population PK model in patients with critical infections to predict bactericidal activity and the development of resistance at different doses of temocillin.

Results: The development of resistant subpopulations was observed within 24 hours in all 4 strains studied. The PK/PD model accurately described the observed bactericidal kinetics and the onset of resistance for both experimental regimens. Simulations indicated dose-dependent bactericidal activity at doses above those typically used, with continuous regimens showing superiority over intermittent regimens. However, the emergence of resistant subpopulations was frequent. For two strains, the bacteriostatic effect over 72 hours was predicted only at doses higher than the maximum recommended doses.

Conclusion: Continuous infusion and a dose of 6 g/day of temocillin eliminate Escherichia coli more effectively than 4 g/day or intermittent infusion, and may increase efficacy in the treatment of systemic infections. However, even higher doses may be necessary to prevent the emergence of resistance.

Introduction: Bacteremia is associated with substantial morbidity and mortality. Early and appropriate antibiotic therapy is important, but its optimal duration remains uncertain.

Method: A multicenter inferiority trial in which hospitalized patients with bacteremia were randomized to receive 7 or 14 days of antibiotic therapy. The choice, dose, and route of administration of antibiotic therapy were at the clinician’s discretion. Exclusion criteria included severely immunocompromised patients, Staphylococcus aureus bacteremia, the presence of foci of infection requiring prolonged treatment, and a single positive blood culture with potential contaminants. The primary endpoint was all-cause mortality 90 days after the first positive blood culture, with a non-inferiority margin of 4%.

Results: A total of 3,608 patients were randomized (7 days of antibiotic therapy, n = 1,814; 14 days, n = 1,794) and were included in the intention-to-treat (ITT) analysis. At enrollment, 55% of patients were in the intensive care unit; 75.4% of bacteremias were community-acquired, 13.4% were hospital- acquired, and 11.2% were intensive care unit-acquired. The most common sites of infection were the urinary tract (42.2%), the abdomen (18.8%), the lungs (13%), a vascular catheter (6.3%), and the skin or soft tissues (5.2%). At Day 90, the mortality rate was 14.5% in the 7-day treatment group and 16.1% in the 14-day group (difference of -1.6%; 97.5% CI: -4.0 to 0.8), demonstrating the non-inferiority of the 7-day treatment. The duration of treatment was longer than that assigned at randomization in 23.1% of patients in the 7-day group and 10.7% of those in the 14-day group. Non-inferiority was confirmed in the per-protocol analysis (difference: -2.0%; 95% CI: -4.5 to 0.6). The results were generally identical for the secondary clinical endpoints and among the prespecified subgroups based on patients, microorganisms, and clinical presentations.

Conclusion: In hospitalized patients with bacteremia, a 7-day course of antibiotic therapy is non-inferior to a 14-day course.

Introduction: People with HIV have a higher risk of anal cancer than the general population. We sought to identify risk factors for anal cancer in people with HIV in order to implement targeted and more effective screening strategies.

Method: A multicenter retrospective study conducted in Spain between 1998 and 2022. Within the PISCIS cohort, ARV-naive HIV patients aged 16 years or older with histologically confirmed anal cancer at the time of follow-up were eligible. Data were collected from each hospital’s registry and centrally validated within the PISCIS cohort. The primary outcome measure was the incidence rate of histologically confirmed anal cancer. A Poisson regression was used to investigate the association between anal cancer and the following risk factors: age, mode of HIV acquisition, CD4 nadir, and time since HIV diagnosis.

Results: Among 14,238 people living with HIV, 107 (0.8%) developed anal cancer during follow-up (median 9.5 years), representing an overall incidence rate of 72.5 cases per 100,000 person-years (95% CI 59.4 to 87.6). Of these 107 patients, 37 (34.6%) died, with 24 (65%) of the deaths attributable to anal cancer. The incidence was highest among HIV-positive individuals with a CD4 nadir < 200/mm³ (incidence rate of 105.0; 95% CI 82.0 to 132.5) and lowest among those with a CD4 nadir > 350/mm³ (2.9; 0.1 to 16.0). Among MSM, the incidence rate was 211.5 (151.1 to 211.7) among those with a CD4 nadir < 200/mm³, 37.6 (16.2 to 74.1) among those with a CD4 nadir between 200 and 350/mm³, and 4.8 (0.1 to 26.9) among those with a CD4 nadir > 350/mm³. Among patients under 30 years of age, no cases of anal cancer occurred among women or men who were not MSM, and only 1 case occurred among MSM with a CD4 nadir > 350/mm³. In the multivariate analysis, people with HIV and a CD4 nadir > 350/mm³ had the lowest risk of developing anal cancer compared with those with a CD4 nadir < 200/mm³ (adjusted incidence rate 0.03; 0.00 to 0.25; p = 0.0010) or between 200 and 350/mm³ (0.30; 0.17 to 0.55; p < 0.0001). Compared with people under 30 years of age, those aged 60 years or older had an adjusted incidence rate ratio of 27.6 (3.7 to 206.9; p = 0.0010), and those aged 45 to 59 had a ratio of 21.6 (3.0 to 156.4; p = 0.020).

Conclusion: A CD4 nadir < 350 mm³, and particularly < 200/mm³, can identify people with HIV who are at increased risk of developing anal cancer. Tailored strategies prioritizing screening of high-risk individuals, based on CD4 nadir, could help optimize available resources. External validation of this study’s data in other cohorts is necessary before updating screening recommendations.

Objectives: Cotrimoxazole may be an alternative to antibiotic treatment for osteoarticular infections involving implanted devices, but there are few published data on its efficacy and tolerability for treating these complex conditions. The objective was to compare the clinical outcomes of patients with implant-associated osteoarticular infections treated with or without cotrimoxazole.

Methods: A multicenter case-control study that included consecutive adult patients diagnosed with osteoarticular infection involving an implant. Each patient treated with cotrimoxazole was matched with two controls, treated without cotrimoxazole, stratified by microbial etiology and age. The primary outcome measure was treatment failure or death.

Results: A total of 150 patients were included, 50 in the cotrimoxazole group and 100 in the control group. The primary outcome occurred in 18% and 21% of patients, respectively (p = 0.66). Cotrimoxazole was not associated with an adverse outcome in the multivariate analysis (adjusted OR 0.8, 95% CI 0.31 to 2.06). The discontinuation rate due to adverse events was similar in both groups (14% vs. 12%), but there were significantly more adverse events in the cotrimoxazole group (34% vs. 18%, p = 0.03).

Conclusion: Cotrimoxazole is an effective alternative strategy for treating osteoarticular infections, even those involving implants; however, its safety profile requires careful monitoring.

Introduction: The specificity of DNA resistance genotyping is hampered by the detection of APOBEC-associated resistance mutations, which are typically carried by proviruses that are incompetent for replication. We investigated the factors associated with the presence of defective sequences in the HIV-1 pol region. We also investigated resistance mutations in the APOBEC context and determined their association with defective sequences.

Methods: We included patients receiving antiretroviral therapy (ART) who achieved virologic suppression (viral load < 200 c/ml) and for whom DNA genotyping was performed, including amplification of sequences encoding protease, reverse transcriptase, and integrase. Sequencing was performed using the Sanger method or Sentosa® NGS with a 20% threshold. All hypermutated sequences and/or those containing at least one stop codon were considered defective.

Results: A total of 613 DNA genotypes were analyzed. Defective sequences were found in 186 cases (30.3%), including 65 protease sequences, 92 reverse transcriptase sequences, and 65 integrase sequences. There was no association — including the amount of proviral DNA— with the detection of defective Pol sequences. A total of 226 ARV resistance mutations in the APOBEC context were identified among all sequences. Most of these mutations (78%) were found in defective sequences. ARV resistance mutations in the APOBEC context were not detected in the plasma viral population and likely do not impact the virologic response to antiretroviral therapy.

Conclusion: Defective pol sequences are not associated with proviral DNA levels and contain most of the ARV resistance mutations in the APOBEC context. These mutations likely have no clinical impact and should not be reported when presenting DNA genotyping

results: Consensus recommendations are needed regarding the reporting of DNA resistance genotype results, particularly for the assessment and interpretation of ARV resistance mutations in the APOBEC context.

Introduction: To date, there have been few real-world data on doravirine. We evaluated the efficacy and tolerability of switching to doravirine treatment in people living with HIV (PLHIV).

Methods: A national, prospective, matched cohort of people living with HIV (PLHIV) with no history of virologic failure who had been on stable antiretroviral therapy (ART) for at least 12 months with a doravirine-free regimen and who switched to a doravirine-containing regimen before September 1, 2020 (exposed group). This group was matched 1:2 with individuals receiving doravirine-free therapy, based on age, sex, mode of HIV acquisition, duration of ARV therapy, calendar period, pre-ART CD4 count and viral load, and ARV class prior to the switch. The primary endpoint was virologic failure (viral load ≥ 200 c/ml) in the ITT population at S104; treatment changes or loss to follow-up were considered virologic failures. The non-inferiority margin was +5%. In the treatment-intent analysis, individuals who experienced a treatment change or were lost to follow-up were censored as of that date.

Results: In total, the doravirine group comprised 590 participants, and the non-doravirine group comprised 1,190 (55.3% on NRTIs). In the ITT analysis, virologic failure was observed in 22.9% and 25.0% of participants, respectively (difference: −2.12%; upper limit of the one-sided 95% CI: +1.40%). In the on-treatment analysis, virologic failure among uncensored patients was 2.2% and 2.9%, respectively (difference: −0.70%; upper limit of the one-sided 95% CI: +0.73%). All participants with a viral load ≥ 200 c/ml achieved virologic resuppression without a change in treatment. No confirmed virologic failure (2 consecutive viral loads ≥ 200 c/ml) was reported. A change in treatment was made in 17.6% and 17.9% of participants, respectively. In the doravirine group, 12.4% discontinued doravirine due to an adverse event: the most common were abnormal dreams (1.7%) and insomnia (1.5%).

Conclusion: Switching to doravirine in virologically well-controlled PLWHIV with no history of virologic failure was non-inferior to continuing treatment without doravirine after 2 years of follow-up in a real-world setting.

Introduction: Most individuals on antiretroviral therapy (ART) have a plasma viral load below the detection limit. However, some participants experience episodes of low-level viremia (LLV), for which the risk factors and clinical significance remain a subject of debate

Methods: We studied participants in the Swiss cohort who initiated ART between July 1999 and April 2023 and had a viral load < 200 copies/mL 6 months after ART initiation. Using longitudinally collected data, we applied a time-updated proportional hazards Cox model to the data over time to determine the association between LTV and subsequent risk of virologic failure, defined as a viral load ≥ 200 copies/mL. VFN was quantified by the time-weighted area under the curve of viral load values, separated by periods of undetectability, and stratified by AUC tertiles.

Results: For the 8,132 participants, the total follow-up was 49,579 person-years (median follow-up: 4.7 years; median number of viral load measurements: 16). The median age was 38 years; 79.5% were men; 74.4% were white; and 45.9% had subtype B. A high viral load was associated with an increased risk of subsequent virologic failure, with the highest category of viral load showing the strongest association (HR of 3.3 compared with an undetectable viral load) among various variables, including race, age, and ART.

Conclusion: A VFN is strongly associated with a subsequent risk of virologic failure, even after adjusting for demographic and clinical characteristics, including adherence and ARV regimen. Detection of a VFN should lead to the implementation of measures designed to reduce the risk of subsequent virologic failure.

Introduction: Treatment recommendations for COVID-19 were issued at the start of the pandemic when knowledge was limited. Real-world data provide useful, up-to-date information. The objective of this analysis was to assess mortality among patients hospitalized for COVID-19 during the Omicron period and treated with remdesivir + dexamethasone versus dexamethasone alone.

Methods: A large, multicenter hospital database in the United States was used to identify adults hospitalized between December 2021 and April 2023 with a diagnosis of COVID-19 who were treated with remdesivir plus dexamethasone versus dexamethasone alone. Patients were matched 1:1 using propensity scores, with stratification by oxygen requirements. A proportional hazards Cox model was used to assess all-cause in-hospital mortality at days 14 and 28.

Results: Among the 33,037 matched patients, 72% were 65 years of age or older, and 78% were white. Remdesivir plus dexamethasone was associated with a lower risk of mortality at Day 14 than dexamethasone alone in all subgroups based on oxygen requirements at Day 0: no oxygen therapy: adjusted hazard ratio 0.79; 95% CI: 0.72 to 0.87; low-flow O₂: 0.70; 0.64 to 0.77; high-flow oxygen/noninvasive ventilation: 0.69; 0.62 to 0.76; mechanical ventilation/ECMO: 0.78; 0.64 to 0.94. Similar results were observed for mortality at Day 28.

Conclusion: Remdesivir plus dexamethasone was associated with a significant reduction in mortality at Day 14 and Day 28 compared with dexamethasone alone in patients hospitalized for COVID-19, regardless of initial oxygen requirements.