AIDS最新文献

Objective: To investigate the relationship of polypharmacy exposure to longitudinal trajectories of global and domain-specific cognitive function in people with HIV (PWH), focusing on the effects of both stable and transitioning polypharmacy regimens.

Design: Longitudinal analyses.

Methods: Longitudinal data from 2173 PWH, including 1017 virally suppressed (VS-PWH), were analyzed using harmonized datasets from the CHARTER, NNTC, and HNRP studies. Polypharmacy was categorized as low (0-4 medications), moderate (5-9), or high (≥10) based on the number of nonantiretroviral therapy (non-ART) medications. Demographically adjusted global and domain-specific T-scores were derived from standardized batteries. To assess the association between polypharmacy and cognitive trajectories, we developed a novel transition-based mixed-effects regression approach that captured both stable and changing patterns of polypharmacy exposure over time, allowing for the assessment of immediate and cumulative cognitive effects of medication burden.

Results: Higher polypharmacy levels were significantly associated with poorer global and domain-specific cognitive function. Participants with high polypharmacy exhibited steeper cognitive declines, while those with low polypharmacy demonstrated stable or modestly improved trajectories. This pattern was similarly observed in VS-PWH. Transitions from low to high polypharmacy resulted in significant global and domain-specific cognitive declines. Conversely, reductions from moderate or high to lower polypharmacy levels yielded cognitive improvements - particularly in motor function - in both PWH and VS-PWH populations.

Conclusion: Polypharmacy imposes a cumulative burden on cognitive function in both PWH and VS-PWH. Higher polypharmacy levels exacerbate cognitive decline, highlighting the necessity of targeted strategies to manage polypharmacy and mitigate its long-term cognitive impact.

Background: This study aims to identify the comparative effects of different drug regimens in treating Mycobacterium avium complex (MAC).

Methods: PubMed, EMBASE, CENTRAL, and EBSCO Open Dissertations were searched in September 2023. We included randomized controlled trials in people with HIV and MAC infection that compared any regimens and reported culture- conversion results. Antibiotic regimens were classified as azithromycin plus ethambutol (AZI+E); clarithromycin plus clofazimine (CLA+CLO); clarithromycin plus ethambutol (CLA+E); clarithromycin plus ethambutol and clofazimine (CLA+E+CLO); clarithromycin plus ethambutol and rifampicin/rifabutin (CLA+E+R); clarithromycin plus rifampicin/rifabutin (CLA+R); clofazimine plus ethambutol (CLO+E); and clofazimine plus ethambutol and rifampicin/rifabutin (CLO+E+R). Risk ratios with 95% confidence interval (95% CI) were estimated using a random-effects model. The effects of treatment regimens were ranked using the surface under the cumulative ranking (SUCRA).

Findings: Of 3611 articles identified, 12 met ( n  = 2987) the eligibility criteria. The following regimens showed higher culture-conversion outcomes (risk ratio [95%CI]) compared to CLA+E: CLA+CLO (1.15 [0.73,1.81]), CLA+E+R (1.09 [0.80,1.47]), CLA+E+CLO (1.01 [0.69,1.46]), CLA+R [0.97 (0.56,1.70]), AZI+E (0.82 [0.60,1.13]), CLO+E+R (0.44 [0.25,0.77]), CLO+E (0.37 [0.19,0.72]). The SUCRA of CLA+CLO (80.9%) aligns with its highest comparative efficacy. The RR of culture conversion to negative was higher in ARV-treated patients. Adverse events were similar across regimens, except for a higher risk with CLO+E+R compared to CLA+CLO (7.21 [1.22-42.64]).

Interpretation: Clarithromycin-based regimens remain the treatment of choice for MAC in people with HIV. Although clarithromycin plus clofazimine appears to be the most effective regimen, other clofazimine-based regimens should not be considered as the initial treatment choice. The effective antiretroviral improving culture-conversion outcomes.

Background: Housing instability and HIV are both associated with early onset of aging-related health conditions, including frailty. However, little is known about the relationship between housing and frailty among people with HIV.

Methods: We analyzed data on adults in HIV care collected during routine clinical visits at 6 sites within the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) between 2019 and 2024. We measured frailty using a previously validated approach, defined as having at least three of four components (fatigue, weight loss, immobility, inactivity) vs. less than three components. Housing status was based on self-perceived living situation in the past month ("Stable," "Unstable," "Homeless," or "Don't know"). We estimated the association between most recent housing status and frailty with prevalence ratios from relative risk regression adjusted for sociobehavioral and clinical characteristics.

Results: Among 6961 people with HIV (84% men, 16% women) with a median age of 52 years (IQR: 40-60), 11% ( n  = 760) were frail and 9% ( n  = 625) were unstably housed (5% unstable, 3% homeless, 1% do not know). Compared to individuals with stable housing, the prevalence of frailty more than doubled among those experiencing unstable housing [prevalence ratio = 2.41, 95% confidence interval (95% CI): 1.95-2.97] or homelessness (prevalence ratio = 2.05, 95% CI: 1.56-2.69). Stratified analyses indicated stronger associations among younger vs. older individuals and among those virally suppressed vs. unsuppressed.

Conclusion: Housing instability and frailty were both prevalent and strongly associated among adults in HIV care, including within younger and virally suppressed subgroups. These findings highlight the importance of social determinants of health for clinical outcomes among all people with HIV.

Objectives: Despite effective antiretroviral therapy, many people with HIV (PWH) experience persistent deficits in attention and working memory. Identifying neurometabolic drivers of these impairments is critical for precision diagnostics and targeted interventions. N-acetylaspartylglutamate (NAAG), the most abundant brain dipeptide and endogenous agonist of metabotropic glutamate receptor 3 (mGluR3), regulates glutamatergic transmission central to these cognitive domains. While prior magnetic resonance spectroscopy (MRS) studies have associated higher NAAG with better cognition, NAAG has never been quantified in cerebrospinal fluid (CSF) of PWH or linked to cognition in this population.

Design: We tested whether CSF NAAG levels relate to domain-specific cognitive function in 28 PWH (plasma viral load <200 cp/ml).

Methods: NAAG was quantified by a sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS-MS) method. Cognition was measured using a Research Domain Criteria (RDoC)-based battery, with principal component analysis deriving domain scores. Pearson correlations and age/viral load adjusted regressions were used to assess NAAG-cognition associations.

Results: Higher CSF NAAG was significantly associated with better spatial attention and working memory ( r  = 0.479, P  = 0.01), independent of age and viral load. In contrast, NAAG levels showed no relationship with verbal attention and working memory or other domains such as verbal episodic memory and motor function.

Conclusion: This is the first study to identify a CSF-based neurometabolic marker linked to specific cognitive domains in PWH, bridging MRS findings to a scalable fluid biomarker platform. NAAG CSF measurement opens new translational pathways for early detection, risk profiling, and glutamatergic-targeted interventions in neuroHIV. Longitudinal studies will determine its prognostic and therapeutic utility.

Objectives: The effect of the M184I/V mutation on the rate of virological failure in people with HIV (PWH) with plasma HIV RNA viral load less than 50 copies/ml switching to a triple-therapy regimen of doravirine+lamivudine+ tenofovir or abacavir has not been evaluated.

Design: A retrospective national study of antiretroviral-experienced PWH who were switched to a doravirine plus lamivudine and abacavir or tenofovir regimen in the context of maintenance (viral load <50 copies/ml) was conducted. Virological failure was characterized by either two consecutive plasma viral loads at least 50 copies/ml or a single viral load at least 200 copies/ml. Viral blip was defined as an isolated viral load 50_200 copies/ml at any time up to month 6 after switching to the doravirine-containing regimen.

Results: Among the 338 PWH, doravirine was mainly associated with tenofovir+lamivudine (311/338, 92.0%). Of these, 45 had a M184I/V mutation before switching. Virological failure at M6 was 14.0 and 17.8% in the absence and presence of M184I/V, respectively, with an adjusted odds ratio (aOR) of 2.409, 95% confidence interval (95% CI) 0.574-10.113, P  = 0.21. The risk of virological failure at M6 was associated with the level of zenith plasma HIV viral load, with an aOR of 1.646, 95% CI 1.163-2.328, P  = 0.0049, per additional log 10 unit. The proportion of viral blip at M6 was 2.4 and 6.7% in PWH in the absence and presence of M184I/V, respectively, with an aOR of 0.818, 95% CI 0.187-3.587, P  = 0.7897.

Conclusion: Among PWH with antiretroviral experience, there was no evidence that switching to doravirine + lamivudine plus tenofovir affected short-term treatment response in individuals harboring HIV M184I/V mutations.

Objective: Exercise intervention programs enhance physical fitness, cognition, neuroimaging measures, and alter the structure of the gut microbiome in individuals without HIV. However, interventional studies exploring the effects of exercise in persons with HIV (PWH) have not included neuroimaging or gut microbiome analyses.

Design: A randomized controlled trial conducted at Washington University in St. Louis, MO, USA.

Methods: 65 PWH (aged ≥40 years, self-reported sedentary lifestyle) were randomly assigned to a 6-month cardiorespiratory and resistance training (EXS) or stretching control (SIS) intervention in a 2 : 1 ratio. Longitudinal change in cognition, cerebral blood flow (CBF), physical and cardiorespiratory fitness, and gut microbiome diversity and composition were examined among participants ( n  = 62) who completed any portion of the intervention (ClinicalTrials.gov: NCT02663934).

Results: Better fitness and better cognitive performance were associated with greater phylogenetic diversity in gut microbiome composition at baseline. Longitudinal findings indicated slight but significant improvements in psychomotor speed and executive function, reductions in body mass index, improvements in physical fitness, and increased gut microbiome diversity. These changes were observed regardless of assigned intervention group. There were no observed changes in CBF for either group.

Conclusions: These findings highlight physical fitness as a modifiable factor in PWH that may improve cognitive performance and change gut microbiome composition. Both interventions were beneficial, suggesting light stretching exercise or study participation alone could have been sufficient to introduce positive cognitive shifts in previously sedentary PWH. Longer interventions with more participants are needed to identify changes in neuroimaging metrics related to brain integrity.

Objectives: An increasing proportion of hospitalized persons with HIV (PWH) in South Africa are virally suppressed. This study aimed to characterize causes of hospitalization, the burden of advanced HIV disease (AHD), and 30-day postdischarge mortality among this patient population.

Methods: We conducted a prospective observational study of adult PWH with a viral load <1000 copies/ml admitted to a public tertiary hospital in Klerksdorp, South Africa from October 2023 to September 2024. Demographic, clinical, and laboratory data were collected, and 30-day follow-up was conducted to assess mortality. AHD was defined as a CD4 count <200 cells/mm 3 or WHO stage 3 or 4 disease based on presence of an AIDS-defining illness. Comparisons between participants hospitalized with AIDS-defining conditions vs. other causes, as well as between decedents and survivors, were conducted using Wilcoxon rank sum and Fisher's exact tests.

Results: Of 1245 hospitalized patients screened, 99 virally suppressed PWH were enrolled. Median age was 45 years; 56% were female. AIDS-defining illnesses, primarily tuberculosis (TB), accounted for 27.3% of hospitalizations. Forty-four participants (44%) met criteria for AHD. Thirty-day mortality was 12.1% (6 in-hospital, 6 postdischarge). Most decedents were <50 years of age and had undetectable viral loads. Factors significantly associated with 30-day mortality included >10 years since HIV diagnosis and initial hemoglobin <12 g /dl.

Conclusions: Despite virologic suppression, PWH who are hospitalized remain at high risk for death-particularly from TB and other AIDS-related illnesses. Strengthening early TB detection, expanding preventive therapy, and improving postdischarge care are critical to improving outcomes in this population.

Objective: Elevated lipoprotein(a) increases the risk of cardiovascular disease, and previous research suggests that lipoprotein(a) levels are higher in patients with chronic inflammatory diseases. Knowledge about lipoprotein(a) in persons with HIV (PWH) is sparse. We aimed to assess if living with HIV is associated with high levels of lipoprotein(a).

Methods: From the Copenhagen Comorbidity in HIV infection (COCOMO) study, we included 789 PWH matched on sex and age with 3156 controls from the Copenhagen general population study. All participants underwent uniform physical examinations, blood sampling and responded to questionnaires regarding lifestyle and health. Lipoprotein(a) was measured using isoform-insensitive immunoturbidimetric assays. High levels of lipoprotein(a) were defined as plasma levels >50 mg/dl.

Results: Living with HIV was not associated with high levels of lipoprotein(a) [adjusted odds ratio (aOR) 0.98 [95% CI: 0.80 to 1.21], P  = 0.88]. Furthermore, none of the examined clinical and demographic factors - including age, sex, diabetes, statin therapy, cholesterol levels, renal function and HIV specific risk factors were significantly associated with elevated lipoprotein(a) levels as well as and none of the examined clinical or demographic risk factors were found to be significantly associated with elevated lipoprotein(a) levels.

Conclusion: In this study, living with HIV was not independently associated with high levels of lipoprotein(a) and none of the examined clinical or demographic risk factors were found to be significantly associated with elevated lipoprotein(a) levels.