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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.

We deployed the VANTAGE (VAN for Transmissible Agent Genomic Epidemiology) mobile system in Lviv, Ukraine, demonstrating end-to-end sequencing of dried blood spot samples within a clinic van usually serving de-occupied and frontline regions. HIV-1 pol sequences were obtained from 50% of samples, all subtype A6. Median time to 100× coverage was 38 min. Phylogenetic analysis revealed a local transmission cluster including a displaced person and the non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation E138A, supporting real-time HIV genomic surveillance in humanitarian crises.

Introduction: We assessed implementation of tuberculosis (TB) services among children living with HIV (CLHIV) (<15 years) in 16 African countries supported by US President's Emergency Plan for AIDS Relief (PEPFAR) between October 2018 and September 2022 [fiscal year (FY) 2019-FY2022).

Methods: We reviewed PEPFAR TB indicators describing symptom screening, treatment initiation, and TB preventive treatment (TPT) initiation and completion among CLHIV. We describe performance of these measures at semi-annual time points from FY2019 to FY2022 with stratification by age, sex, geographic region, and antiretroviral therapy (ART) status for FY2022.

Results: During FY2019-FY2022, the proportion of CLHIV with a positive TB symptom screen was low, ranging from 2.5 to 4.1%, while TB treatment initiation among those who screened positive fluctuated from 19 to 43%. Similarly, TPT initiation among CLHIV newly initiating ART fluctuated during this time, ranging from 13 to 37%, while TPT completion rose from 55 to 85%. In 2022, 80% of CLHIV were screened for TB and 3.6% had a positive symptom screen. Among those, 15% of CLHIV already on ART and 40% of CLHIV newly initiating ART were started on TB treatment. In 2022, among CLHIV newly initiating ART, 37% started TPT within 6 months, and 84% completed the full course of TPT.

Conclusion: TB screening and screening positivity were suboptimal. CLHIV starting TB treatment following positive symptom screen was higher than expected, especially among those newly initiating ART. Most CLHIV did not start TPT within 6 months of ART initiation. These findings suggest that programs are missing opportunities to diagnose and prevent TB in CLHIV.

Objective: To assess hepatitis B virus (HBV) monitoring, HBV reactivation and hepatitis flares during tenofovir interruptions among people with HIV and HBV.

Design: Cohort study of electronic health records.

Methods: All tenofovir (tenofovir disoproxil fumarate and tenofovir alafenamide) interruptions among people with HIV and positive HBV surface antigen (HBsAg) or positive HBV core antibody (HBcAb) were categorized by reactivation risk [high: HBsAg+; moderate: HBsAg-/HBcAb+/surface antibody (HBsAb) negative; low: HBsAg-/HBcAb+/HBsAb+]. Incidence rates of HBV reactivation and hepatitis flare were assessed with Poisson regression.

Results: Among 5343 individuals with HIV and HBV, there were 6252 tenofovir interruptions (11% high risk, 19% moderate risk, 69% low risk). During the interruptions, HBV DNA/HBsAg testing was infrequent (high: 52%/25%; moderate: 8%/31%, low: 5%/28%), although alanine transaminase (ALT) testing was performed during nearly all interruptions. The HBV reactivation rate was 9.59 per 100 person-years [95% confidence interval (CI): 7.91-11.64] during high-risk, 0.58 (0.36, 0.91) during moderate-risk, and 0.04 (0.02, 0.11) during low-risk interruptions. The HBV reactivation with hepatitis flare incidence rate was much lower, especially in the high-risk group (3.06 per 100 person-years; 95% CI: 2.19-4.29).

Conclusions: In this large US cohort of people with HIV and HBV, tenofovir interruptions were common and HBV monitoring was sub-optimal. HBV reactivation rates were highest among the high-risk group, but much lower among the moderate-risk and low-risk groups. However, some reactivations were likely missed due to low monitoring frequency. Primary and HIV care providers must incorporate HBV monitoring in their standard of care and proceed with caution if considering a tenofovir interruption for people with HIV and HBV.

Background: HIV genetic diversity has increased over time, with recombinant forms becoming more prevalent and complicating subtype classification and surveillance, particularly in low-and-middle income countries (LMICs). Accurate subtyping is critical for surveillance, vaccine design, and cure strategies, but its reliability depends on methodological choices — the genomic region sequenced, laboratory methods employed, and the subtyping tools used. This study evaluates how these methodologies influence reported recombinant form prevalence across regions.

Methods: This systematic review included over 400 peer-reviewed studies published between January 2010 and June 2021 that reported HIV subtype prevalence across diverse geographic regions. Data on subtyping methodologies were also extracted. To explore associations with recombinant form prevalence, three generalized linear mixed models were developed for meta-analysis.

Results: Our findings show that Sanger sequencing of the pol region, analyzed using tools from the Los Alamos National Laboratory, remains the most widely used subtyping methodology. Over time, there has been a steady increase in studies reporting HIV subtype diversity. In the meta-analysis, specific genome regions and subtyping tools were positively associated with recombinant form prevalence. Despite controlling for region, certain areas remained positively or negatively associated with recombinant form prevalence.

Conclusions: This review highlights the methodological challenges of HIV subtyping and recombinant form detection, which are critical for surveillance, vaccine development, and cure strategies. We highlight the urgent need for accessible, reliable subtyping tools and enhanced capacity-building—particularly in LMICs, where high viral diversity overlaps with the greatest burden of disease.