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Objective: Examine the associations of gait speed with global and domain-specific neurocognition in older people with HIV (PWH) versus people without HIV (PWoH).

Methods: Participants included 285 PWH and 214 PWoH 50 years and older (Mage = 60.1, SD age = 7.1) who completed a gait examination and a comprehensive neurocognitive assessment.

Results: Gait speed was significantly slower in PWH ( M = 3.3 s, SD = 1.1) than PWoH ( M  = 3.0 s, SD  = 0.9; P  = 0.006). Slower gait speed was significantly associated with poorer global neurocognition ( β = -0.17, P  = 0.009) and deficits in multiple neurocognitive domains, including verbal fluency, executive functioning, processing speed, and motor skills, after adjusting for sociodemographic, HIV-related, and medical characteristics in PWH. A significant interaction between gait speed and HIV status emerged for verbal fluency, suggesting differential cognitive impacts ( β = -0.45, P  = 0.008).

Conclusions: Our findings highlight nuanced relationships between gait speed and neurocognition, emphasizing the need for longitudinal research to establish causal mechanisms and potential clinical screening approaches.

Objectives: Tobacco smoking and alcohol use may negatively influence HIV care, but associations have not been examined across cohorts.

Design: Multisite international collaboration of cohort studies.

Methods: People with HIV (PWH) were included from 11 cohorts; 5 North American and 6 Western European. Exposures were harmonized smoking and alcohol measures (2010-2018). Loss to care was defined as not having 2+ HIV care visits (HIV RNA and/or CD4 measurement dates) at least 60 days apart, within 12 months following alcohol measure date; HIV viral nonsuppression was defined as >200 copies/ml. Adjusted prevalence ratios (PRs) were estimated using modified Poisson regression; pooled effect estimates and the heterogeneity measure ( I2 ).were derived from a random-effect meta-analysis.

Results: Among 83 102 PWH (87.4% male, 46.1% white); 43.7% currently smoked, 44.5% reported low/moderate drinking, 6.9% heavy drinking, 48.6% did not drink. PWH who currently smoked had higher risk of loss to care than nonsmoking PWH (pooled PR [95% CI] = 1.12 [1.08-1.16], I2  = 18.1%); those with heavy drinking had higher risk than those with low/moderate drinking (1.13 [1.03-1.25], I2  = 57.8%). PWH who currently smoked had higher risk of viral nonsuppression than nonsmoking PWH (1.44 [1.25-1.67], I2  = 90.6%); those reporting heavy drinking had higher risk than those with low/moderate drinking (pooled PR [95% CI] = 1.18 [1.02-1.37], I2  = 68.9%). PWH who reported heavy drinking and current smoking, in comparison to low/moderate alcohol use but no current smoking, had highest risk of viral nonsuppression (pooled PR [95% CI] =1.74 [1.37-2.22]), I2  = 81.8%.

Conclusions: Smoking and unhealthy alcohol use were associated with HIV loss to care and viral nonsuppression, with variability between cohorts.

Introduction: Long-acting regimens (LAR) are emerging as a promising strategy to enhance treatment satisfaction and improve quality of life of people with HIV. A comprehensive understanding of treatment preferences is essential to effectively address the needs and expectations of people with HIV.

Design: A discrete choice experiment (DCE) was conducted to identify preferences for LAR among people with HIV.

Methods: Our study was conducted at the HIV-outpatient clinic of the Amsterdam UMC between May and August 2024. The survey included 24 choice scenarios, each presenting participants with two unlabeled treatment options. Six attributes were evaluated: mode of administration, administration frequency, risk of viral resistance, risk of side effects, setting of administration, and allowance for delayed dosing. Data were analyzed using a panel data mixed logit choice model in Stata 17.

Results: A total of 259 participants completed the DCE. Eighty-eight percent were cisgender male, with a median age of 57 years [23-84]. Mode of administration emerged as the most significant factor influencing treatment choice, with tablets being the most preferred option. Participants generally favored regimens with lower administration frequency and a lower risk of viral resistance. Allowance for delayed dosing, the setting of administration, and the risk of side effects had the least influence on treatment choice.

Conclusion: Our results indicate that treatment choice is primarily driven by the mode of administration, with tablets being the most preferred option. This is followed by dosing frequency and risk of viral resistance. These findings offer important insights for optimizing treatment approaches and advancing person-centered care strategies.

Background: The triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, has shown promise in predicting various noncommunicable diseases. This study investigated the association between the TyG index and the incidence of type 2 diabetes mellitus (T2DM) within a 13-year retrospective longitudinal cohort of people with HIV (PWH).

Methods: This retrospective cohort study utilized data from the China National Free ART Program (CNFAP) in Guangxi, enrolling PWH who initiated ART between 2010 and 2022. The primary exposure, TyG index, was calculated as ln [TG (mg/dl)  × FBG (mg/dl)/2]. The outcome, T2DM, was defined as two consecutive FBG measurements at least 7 mmol/l. Gaussian mixture model (GMM)-based multitrajectory analysis identified TyG trajectories. Multivariate Cox proportional hazard models were used to estimate the associations between TyG trajectories and the risk of T2DM.

Results: A total of 15 370 patients were included, with 69.9% men, and a median age of 45 at ART initiation. Over 63 232 person-years of follow-up, 22.7% (3493/15 370) developed T2DM.The 'high Inverted U-shape' TyG trajectory was significantly associated with T2DM [ adjusted hazard ratio (aHR): 2.37, 95% confidence interval (CI): 2.21-2.54]. Additionally, the TyG index outperformed FBG in predicting T2DM at both 5 and 10 years (5-year AUC: 0.640 vs. 0.621, P  = 0.003; 10-year AUC: 0.655 vs. 0.592, P  < 0.001).

Conclusion: This study highlights the clinical value of the TyG index as a predictive marker for T2DM in PWH, suggesting its potential for early risk stratification.

Background: Symptomatic cerebrospinal fluid (CSF) escape is an uncommon presentation in people with HIV with undetectable or low-level HIV RNA while on combination antiretroviral treatment (cART). Only one case has been reported in a patient receiving bictegravir-based therapy so far.

Methods: We looked for patients presenting with neurological symptoms while on Tenofovir Alafenamide/Emtricitabine/Bictegravir and who were confirmed to have a CSF HIV RNA above plasma HIV RNA.

Results: One patient presented with confusion and cognitive changes; her plasma and CSF HIV RNA were 486 and 1400 copies/ml. In CSF but not plasma, next-generation sequencing identified resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (K70N at 22% and T215S at 92%) and nonnucleoside reverse transcriptase inhibitors (E138K at 18%). One patient presented with lower limb pain and weakness: his plasma and CSF HIV RNA were 7410 and 88 000 copies/ml. No RAMs were found but biomarkers suggested intrathecal immune activation and neuronal damage. Intensification with doravirine led to suppression of plasma viremia within 3 months.

Conclusion: This case series suggests that symptomatic CSF escape is possible even with modern cART and that lumbar punctures may be needed in the presence of unexplained neurological/neuropsychological symptoms.

Objectives: Associations between inflammatory markers and prevalent or incident frailty, cognitive impairment, clinical events, and mortality in older people with HIV are poorly understood.

Design: An observational cohort study.

Methods: Participants aged at least 50 years from the ACTG HAILO cohort study were included. Participants completed annual evaluations for cognitive impairment and frailty. Clinical events included non-AIDS-defining cancers, diabetes, and cardiovascular, liver, and kidney diseases. Associations between inflammatory markers (hsCRP, IL-6, TNFR1, CXCL-9, and inflammatory index score [IIS]) at baseline and prevalence and incidence of frailty, cognitive impairment, any clinical event, and non-accidental mortality were examined. We used 10-fold cross validation to evaluate whether the combination of inflammatory markers and frailty improved the ability to predict incident outcomes.

Results: Among 484 participants (17% assigned female at birth, 25% Black, and 20% Hispanic), median age was 56 years. Median BMI was 27 kg/m 2 , median CD4 + cell count was 627 cells/μl, and 95% had HIV-1 RNA less than 200 copies/ml. HsCRP, IL-6, TNFR1, CXCL-9, and IIS were associated with increased risk of prevalent frailty and clinical events, but not cognitive impairment. CXCL-9 (Q4 vs. Q1) and TNFR1 were associated with an increased incidence of both frailty and clinical events; Q4 vs. Q1 of the IIS was associated with clinical events; increased inflammatory markers (except CXCL-9) were associated with an increased risk of mortality. TNFR1 combined with frailty modestly improved the predictability of incident clinical events and mortality over frailty alone.

Conclusion: Several inflammatory markers were associated with increased risk of frailty, clinical events, and mortality, but not cognitive impairment.

Objective: To evaluate subcutaneous anterior abdominal injections of long-acting cabotegravir plus rilpivirine (CAB + RPV LA) in participants with more than 3 years' experience with intramuscular injections in the Phase 3 FLAIR (NCT02938520) study.

Design: Substudy of a phase 3, randomized, open-label, multicenter, noninferiority study.

Methods: Substudy phases included screening/intramuscular gluteal injection, subcutaneous injection [day 1-week (W) 8], and return to gluteal injection (W12-W20). The injection schedule was unchanged from the main study (every 4 weeks). Outcomes included pharmacokinetics, safety, tolerability, efficacy, and patient-reported outcomes.

Results: Overall, 93 participants were enrolled and received subcutaneous injections; 19% were female (sex at birth). CAB and RPV plasma exposures were generally comparable between subcutaneous and intramuscular injections, with 90% confidence intervals of geometric least squares mean ratios all within 0.80-1.25 boundary of no difference. Pain (48%), nodules (34%), and erythema (26%) were the most frequently reported subcutaneous-related injection site reactions (ISRs). Median durations of nodule and induration were longer with subcutaneous vs. intramuscular administration. Five (5%) participants withdrew due to a subcutaneous-related ISR. Few participants (2%) had HIV-1 RNA at least 50 copies/ml after subcutaneous injections. Participants reported greater pain and lower acceptability of ISRs following subcutaneous vs. intramuscular administration; 59% of participants preferred intramuscular injections.

Conclusion: Pharmacokinetics and efficacy were similar between CAB+RPV LA subcutaneous and intramuscular administration; however, due to the higher incidence and duration of ISRs, along with lower tolerability and acceptability of subcutaneous injections, subcutaneous administration with the current CAB LA and RPV LA formulations is not being evaluated further.

Objective: This study aimed to identify risk factors associated with the onset and progression of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in People Living with Human Immunodeficiency Virus (PLWH).

Methods: Clinical and laboratory data were retrospective collected at 6 months, 1, 1.5, 2, and 3 years after ART initiation. Multivariable logistic regression was employed to identify MAFLD risk factors and evaluate ART's influence.

Results: Among the 740 participants (95% male, mean age 36.58 ± 13.93 years), with an average ART duration of 3.33 ± 4.56 years. Laboratory data at 6 months showed a CD4 count of (356.95 ± 98.76) cells/mm3, body mass index (BMI) of (22.87 ± 7.47) kg/m2, triglycerides (TG) of (1.53 ± 0.98) mmol/L and low-density lipoprotein cholesterol (LDL-c) of (2.45 ± 0.71) mmol/L. MAFLD detection rates by Hepatic Steatosis Index (HSI) and Zhejiang University indices (ZJU) increased with longer ART duration. Patients with>10% weight gain showed a notable rise from 48.80% at baseline to 87% after 3 years of ART. Independent risk factors for MAFLD included female, type 2 diabetes mellitus (T2DM) prior MAFLD, baseline BMI>24 kg/m2 and TG≥1.7 mmol/L, weight gain of 5-10% or >10% within one year, BMI≥24 kg/m2 and TG≥1.7 mmol/L at year 1. Protective factors included age>65 years, AZT and 3TC-based therapies.

Conclusion: The prevalence of MAFLD as assessed by the HSI and ZJU indices increases steadily with ART and is strongly related to weight gains. These findings validate the effectiveness of these non-invasive tools for identifying key risk factors and underscore the necessity of continuous weight monitoring in contemporary ART-treated patients.