Discovering metabolic pathways associated with immune activation in people living with HIV following ChAdOx1 nCoV-19 vaccination using mass spectrometry.

Diagnostic performances of Anyplex MTB/NTM Real-time detection vs Xpert® MTB/RIF Ultra for tuberculosis among people living with human immunodeficiency virus with low CD4 count.

Dysregulated inflammatory cytokines in MSM living with HIV who exhibited suboptimal immune reconstitution despite antiretroviral therapy (ART).

Background AIDS-related non-Hodgkin lymphoma (AR-NHL), a leading malignancy among people living with HIV (PLWH), may not receive standard intensive curative therapies as the general population due to immune deficiency concerns, even in the combined antiretroviral therapy (cART) and immunochemotherapy era. Thus, a comprehensive understanding of T-cell subsets landscapes is urgently needed to grasp the complex and dynamic role of the immune system in AR-NHL patients’ survival. Materials and methods This longitudinal cohort study enrolled 31 de novo adult AR-NHL patients and 52 HIV-negative NHL controls. Multi-color flow cytometry profiled peripheral blood immunophenotypes at baseline and during immunochemotherapy. Univariate and multivariate Cox regression analyses evaluated associations between baseline risk factors and clinical outcomes. Results AR-NHL patients exhibited comparable 1-year overall survival (71.0% vs. 74.8%) and progression-free survival (60.4% vs. 64.6%) to HIV-negative NHL individuals. Baseline β2-microglobulin (β2-MG), erythrocyte sedimentation rate, and EBER positivity were higher in AR-NHL. AR-NHL revealed persistent immune senescence during immunochemotherapy, including reduced CD4+ T cells, lower CD4/CD8 ratio, decreased Tregs, naïve CD45RA+, and memory CD45RO + CD4+ T cells, alongside elevated Tregs/CD4, CD8+, CD8 + CD28+, and CD8 + CD28− T cells, highlighting the complex HIV-driven immune compromise. Multivariate analysis identified baseline circulating CD8 + CD28− T cells as an independent predictor of inferior prognosis in AR-NHL, correlated with aggressive disease markers such as elevated β2-MG, hypoproteinemia, decreased CD4/CD8 ratio, high International Prognostic Index score, and EBER positivity. Conclusions AR-NHL patients warrant standard full-dose cancer therapy to improve prognosis despite immunocompromised and immunosenescence phenotypes. CD8 + CD28− T cells serve as an independent prognostic biomarker for AR-NHL, potentially associated with chronic immune activation and viral exposure. Our data suggest that characterizing T-cell subsets may enhance understanding of immune dynamics in AR-NHL, providing a foundation for exploring personalized approaches to infection prophylaxis.

Despite global progress against HIV/AIDS through widespread antiretroviral therapy (ART) access, treatment success still hinges on adherence, shaped by the knowledge, attitudes, perceptions, and practices of people living with HIV (PLHIV). In densely populated Lagos, Nigeria, where the HIV burden remains high, this study assessed factors influencing ART adherence to inform future strategies for improving treatment outcomes. A multicenter, descriptive, cross-sectional study design was employed. Data were collected using a structured, self-administered questionnaire administered to consenting individuals living with HIV who had been receiving antiretroviral therapy for at least three months. 600 pre-tested questionnaires were administered. Of these, 513 were completed and analyzed, resulting in a response rate of 85.5%. Respondents are PLHIV attending antiretroviral clinics across six selected secondary healthcare facilities in Lagos. Data collection took place between February 2024 and April 2024. Descriptive statistics were generated using SPSS version 23. Pearson correlation and multiple linear regression were conducted to examine relationships among variables. The mean age of respondents was 43 years, with 74.9% (384/513) being female. Approximately 94% of participants demonstrated satisfactory knowledge of ART. Additionally, 81.1% exhibited satisfactory attitudes toward treatment, while 68.4% had poor perceptions of their medications. Nearly half of the respondents (45.4%, 233/513) reported storing their medicines in a concealed location within their residence. A significant but weak negative correlation was found between knowledge and perception of PLHIV towards ART (r(513) = -0.129, p = 0.003). No significant correlation was found between their knowledge and attitude towards ART (r(513) = 0.018, p = 0.683). Multiple linear regression analysis revealed a statistically significant negative association between respondents' perception of ART and their knowledge of ART (β = -0.609, p = 0.003), indicating that less favorable perceptions were associated with lower levels of knowledge about ART. People living with HIV in Lagos State demonstrate satisfactory knowledge and attitudes toward antiretroviral therapy; however, negative perceptions about their medications remain prevalent. HIV-related stigma continues to influence key behavioral practices, such as medication concealment and nondisclosure of HIV status. Strengthening patient-centered education and stigma-reduction efforts may enhance ART adherence and improve long-term treatment outcomes in this population.

The accuracy of Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) to predict liver steatosis in people living with HIV (PLWH) remains poorly studied in low- and middle-income countries (LMICs). We assessed their diagnostic performances in a multiregional cohort. This cross-sectional analysis included PLWH aged ≥40 years on antiretroviral therapy for ≥6 months at enrolment (2020-2023) in the Sentinel Research Network (SRN) of IeDEA consortium, across 12 HIV clinics in Asia-Pacific, Americas, and central, East, southern and West Africa regions. Liver steatosis was defined based on Controlled Attenuation Parameter (CAP) ≥248 dB/m using vibration-controlled transient elastography. HSI was evaluated in the overall population, while FLI was assessed and compared to HSI in a subset of participants with available data. Model discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and model calibration with calibration plots. A decision curve analysis was performed to compare their clinical utility. Among 2,195 PLWH assessed using CAP, 624 (28.4%) presented with liver steatosis. HSI showed acceptable discriminative ability (AUROC = 0.74) but poor calibration, generally overestimating the risk, except in Asia-Pacific region. FLI performed better than HSI (AUROC = 0.80, p < 0.001), and demonstrated good calibration except in sub-Saharan Africa. Both scores showed high clinical utility, with FLI demonstrating a greater net benefit when compared with HSI. FLI demonstrated higher accuracy and clinical utility within a subgroup of regions. However, the limited performance of FLI and HSI in sub-Saharan populations highlights the need to adapt existing tools or develop new predictive models tailored to regional contexts.

Access to HIV care is a persistent challenge in rural settings. Arkansas has one of the highest proportions of rural residents in the U.S., yet data on statewide engagement and retention in HIV care are limited. This study used the Arkansas All-Payer Claims Database (APCD), a longitudinal database of medical, pharmacy, and enrollment claims from Medicaid and most commercial insurers, to evaluate the HIV care continuum and spatial access to providers. We identified people living with HIV (PLWH) from 2013–2017 using an algorithm requiring ≥2 HIV diagnosis claims or ≥1 prescription for antiretroviral therapy (ART). Engagement in care was defined as ≥1 CD4 or viral load (VL) test in a calendar year, while retention was defined as ≥2 tests in a year. Geospatial accessibility to HIV care at the county level was assessed using ArcGIS. A total of 5,033 PLWH in Arkansas were identified across the 5-year period. Only 18–21% of this population received CD4 testing and 47–51% received VL testing annually. ART prescription fills ranged from 61–88% annually. HIV testing rates among the broader insured population were also low, particularly in rural counties. There were 92 unique physicians with HIV-related care claims during the study period, equating to approximately 1 provider per 50 PLWH. Spatial access and care engagement were lower in rural counties. Significant gaps exist in HIV care engagement and retention in Arkansas, with notable gender and rural/urban disparities. Targeted interventions are crucial to address these disparities and end the HIV epidemic in the state.

Comparison of the Exercise Vital Sign Questionnaire With Accelerometry and Physical Activity Behaviors in People Living With HIV in New York City: A Cross-Sectional Study.

The global prevalence of the human immunodeficiency virus (HIV) continues to increase with approximately 39.0million reported cases. Luckily, administering antiretroviral therapy (ART) shows positive effects in viral suppression and immune reconstitution leading to an extended lifespan. Despite such positive outcomes, prolonged use of ART has been implicated in aggravating metabolic complications related to weight gain, leading to the development of type 2 diabetes mellitus (T2DM). Thus, this systematic review looks at the potential role of Body Mass Index (BMI) and waist circumference (WC) as predictors for the development of T2DM among PLWH on ART. This systematic review synthesised findings from 30 studies published between 2007 and 2024 that examined the associations between BMI, WC, and T2DM risk among people living with HIV (PLWH) on ART. Existing literature was retrieved through electronic databases including PubMed and Google Scholar. All literature deemed eligible for inclusion in the present study were assessed for their quality of evidence and risk of bias utilizing the Downs and Black checklist. The prevalence of T2DM ranged from 1.5% to 62.4%, with most studies reporting a positive association between increased BMI and T2DM. A high BMI was consistently associated with a 1.04- to 12.43-fold increased risk of T2DM or insulin resistance. Central obesity and WC were less frequently reported but demonstrated variable associations, with some studies linking increased WC to contribute a 2.34-fold risk to the development of T2DM, while others reported an inverse or no association. Longer duration on ART, particularly > 5 or > 10 years, and specific ART regimens (e.g., those containing didanosine, stavudine, or PIs) were often associated with increased T2DM risk. Several studies also identified age, male sex, and ethnicity as independent risk factors. Body Mass Index is a consistent and potential predictor of T2DM among PLWH on ART, while the role of WC appears variable and context dependent. These findings support the inclusion of BMI monitoring in HIV care, though further research is needed to clarify the predictive utility of WC and refine screening thresholds for this population. Not applicable.

BackgroundHIV self-testing (HIVST) enhances case diagnosis, but information on its integration for index testing to partner notification is limited. Assessing the acceptability and feasibility of index HIVST and partner testing among people living with HIV (PLHIV) and undiagnosed key populations is critical to ending the AIDS epidemic.MethodsA mixed-methods systematic review using a convergent segregated approach was conducted using the Joanna Briggs Institute’s methodology. Four databases were used to conduct a literature review from October 2023 to March 2024, which included studies published between 2016 and 2023. Rayyan software was used for full-text screening. Meta-analysis was deemed infeasible; however, a qualitative meta-aggregation approach was conducted.ResultsA total of 4076 studies were retrieved, and 76 studies met the inclusion criteria after a full review. Most of these studies were from the African region, with only one from South Asia and a few from East Asia. Index HIVST and partner testing were found acceptable and feasible among PLHIV and key populations. Despite low partner elicitation ratios through assisted partner notification, a higher positivity rate was noted among notified individuals. Preferences for index HIVST and partner testing varied, with more inclination for assisted and passive partner referrals to overcome the risk of HIV status disclosure. Assisted partner notification (aPN) showed a low cost per infection averted, indicating it’s a cost-effective intervention. Available evidence was skewed towards married couples, with less evidence on unmarried and undiagnosed key populations.ConclusionThe index HIVST was found to be acceptable and feasible in reaching index partners, including untested and undiagnosed partners of key populations, when various testing approaches are used. Understanding the index HIVST among unmarried HIV index cases, and partner testing of undiagnosed key populations is important, particularly in the Southeast Asian region, to bridge the current HIV case detection gaps. Although no specific cost-effectiveness studies were found for the index HIVST, the aPN was found to be cost-effective.Study registrationPROSPERO Number: CRD42023475417 dated 2023. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023475417.

Salmonella gastrointestinal infections are common in low- and middle-income countries; however, there is limited data on the clinical presentation and microbiological characteristics of invasive Salmonella disease in Latin America. A cross-sectional study was conducted, including all patients with Salmonella spp. isolated from usually sterile sites at our center from May 2016 to June 2025. Data on demographics, comorbidities, immunological status, symptoms, treatment, and outcomes were collected from medical records. The isolated serogroups and their antimicrobial resistance patterns were analyzed using historical data from the Bacteriology Laboratory electronic database. Descriptive statistical methods were used for data analysis. A total of 77 cases of invasive Salmonella infection were identified. Most patients were male (76.6%), with a median age of 33 years. HIV infection was present in 80.5% of cases, and 88.7% of these individuals had advanced disease. Fever was the most frequent symptom (85.7%), and 10.4% required admission to the intensive care unit. Overall mortality was 13%, and all fatal cases occurred among people living with HIV (PWH). The most common treatment was third-generation cephalosporins (58.4%). Resistance to aminoglycosides was documented in all isolates; 52.3% were resistant to trimethoprim-sulfamethoxazole and 6% to ceftriaxone. Ciprofloxacin non-susceptibility reached 64.8%. Multidrug resistance was observed in 12.6% of isolates. Invasive Salmonella disease primarily affected immunocompromised individuals, particularly PWH, with fever and bacteremia being the predominant clinical manifestations. Although multidrug resistance was relatively low, the high prevalence of ciprofloxacin non-susceptibility highlights the need to revise regional empirical treatment strategies.

Antiretroviral therapy (ART) has significantly improved the survival and quality of life of people living with HIV (PLHIV). However, many still face persistent physical, emotional, and social challenges. Integrating psychological treatments into HIV care has demonstrated potential for enhancing mental health, improving treatment adherence, and achieving better clinical outcomes. While the effectiveness of these interventions is well-documented, evidence on their cost-effectiveness remains limited and lacks systematic synthesis. This study addresses this gap by evaluating the current evidence on the cost-effectiveness of psychological treatment and support interventions for PLHIV. A comprehensive search was conducted in PubMed, PsycINFO, Embase, and EconLit via EBSCO for English-language, peer-reviewed studies on the cost-effectiveness of psychological interventions for individuals living with HIV/AIDS. No restrictions were placed on the publication year. Searches were performed in January, June, August, and October 2024, supplemented by citation tracking. Three reviewers independently screened studies in two stages, resolving disagreements through discussion. Data were extracted using a standardized table aligned with Joanna Briggs Institute guidelines to capture study characteristics, interventions, outcomes, and methodologies. Study quality was assessed using the Quality of Health Economic Studies (QHES) instrument. Out of 3,410 records identified, 2,852 remained after duplicate removal, and eight studies met the inclusion criteria. Studies were conducted in the USA (n = 3), Uganda (n = 3), the Netherlands (n = 1), and Tanzania (n = 1), using randomized controlled trials, observational designs, and modeling approaches. Seven of the eight interventions demonstrated cost-effectiveness when evaluated against country-specific willingness-to-pay thresholds. Reported incremental cost-effectiveness ratios ranged from $13-$397 per DALY averted in low-income settings and $13,316-$36,166 per QALY gained in high-income settings, consistently falling below accepted thresholds. Several interventions showed high probabilities of cost-effectiveness (≥ 94%) and, in some cases, cost savings. One psychosocial group intervention in Tanzania exceeded GDP-based thresholds but was still considered a potentially affordable alternative given limited access to mental health services. The findings indicate that psychological treatment and support interventions for PLHIV are generally cost-effective across both developed and developing settings, enhancing mental health outcomes while optimizing healthcare resource use. However, the evidence base remains limited to eight studies from four countries, underscoring the need for further research across diverse contexts to reinforce the economic case for integrating psychological services into HIV care frameworks.

As people living with HIV (PLWH) age, they face various stressors that may negatively affect HIV treatment adherence and management. Resilience and personality characteristics have demonstrated associations with better health outcomes among people with various health conditions. The present study examines the association between dispositional resilience, the Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, neuroticism), and locus of control with self-reported perceived HIV treatment management ability among middle-aged and older PLWH. This cross-sectional study included 174 PLWH aged 40 years and older. Treatment management ability was measured by a composite of three HIV health-related perceived treatment management ability measures. After conducting correlations to determine independent variables, a multivariable linear regression predicting treatment management ability was conducted with resilience, all Big Five personality traits, locus of control, and conceptually relevant covariates (health literacy, race, SES, substance use, depression), using a stepwise approach to determine the optimal number of predictors. The overall model predicting treatment management ability was significant, (F(5,142) = 20.348, p < .001, Adjusted R2 = 0.40), and this model retained resilience, openness, depression, and health literacy. Follow up mediation analysis found that resilience partially mediated the association between openness and treatment management ability. Resilience, openness, depression, and health literacy are important psychosocial factors related to treatment management ability. Interventions targeting resilience, openness to new information, depression, and health literacy may improve HIV treatment management abilities and ultimately health outcomes among older PLWH.

Background/Objectives: Both HIV infection and antiretroviral therapy contribute to dyslipidemia and abnormal body fat distribution in people living with HIV (PLWH). Exercise training is an effective intervention to protect against these metabolic changes. However, little is known about the mechanisms underlying the impact of exercise training on lipid metabolism in PLWH. This study aimed to comparatively evaluate the effect of high-intensity functional circuit training on the plasma lipidome of PLWH and HIV-negative subjects (control). Methods: PLWH (n = 13) and control (n = 14) were submitted to 8 weeks of exercise training. Body composition, anthropometric, and biochemical parameters were measured. Plasma was obtained in a fasting state for lipidomic analysis. Results: Anthropometric and biochemical parameters revealed lower levels of leptin, HDL-C, body fat %, and BMI combined with elevated aspartate transaminase (AST) and Homeostasis Model Assessment of β-cell function (HOMA_beta) in PLWH when compared to control subjects that persisted from baseline to post-exercise training. Nonetheless, contrasting levels of adiponectin, fasting insulin, and phosphatidylcholine-containing lipids observed at baseline were equalized after training in PLWH. In control subjects, significant reductions in concentrations of triglycerides alongside phosphatidylinositol and glycosylated ceramides were observed post-exercise training. By contrast, PWLH displayed an increase in diglycerides, acylcarnitines, and free cholesterol levels after exercise training, together with decreased concentrations of free fatty acids, cholesteryl esters, and glycosylated ceramides. Conclusions: In addition to specific lipidome alterations in each group, particularly driven by improved insulin resistance in PLWH, this study showed concomitant modulation of several glycerophospholipids and sphingolipids, suggesting health-promoting effects of short-term exercise training. Collectively, these modulated lipid species represent interesting targets for future lipidomic-based studies evaluating not only the effects of exercise training but also the molecular mechanisms resulting in a healthier plasma lipidome profile.

The immune response of people living with HIV (PLHIV) coinfected with intestinal and/or blood helminths is still understudied in Gabon. The aim of this study was to compare IgE levels between HIV-positive and HIV-negative people depending on parasite carriage. Samples from PLHIV and HIV-negative individuals, carriers or not of intestinal parasites and/or microfilariae and/or Plasmodium falciparum, were used as the study materials. The total IgE assay was performed using the VIDAS PC. Samples from 152 participants were included in the study, 91 HIV-positive and 61 HIV-negative. Overall, 13.1% (n=20/152) of the samples were infected with soil-transmitted helminths (STH), 29.0% (n=44/152) with intestinal protozoa, 18.4% (n=28/152) with P. falciparum and 36.8% (n=56/152) by blood microfilariae. Median total IgE tended to be higher in HIV-negative participants compared with PLHIV (1287.0 kUI/L; IQR 379.2-3975.2 kUI/L vs 660.3 kUI/L; IQR 236.9-3445.7 kUI/L) (p=0.07). Carriers of STH had higher IgE levels than the other groups (p=0.02). There was a positive correlation between malaria parasitaemia, age and IgE levels in the HIV-negative group (rho=0.283; p=0.0008 and rho=0.5; p=0.0003, respectively). This study showed that PLHIV had lower IgE levels than HIV-negative people. Mansonella perstans and STH were associated with elevated IgE values, requiring further studies to better understand their immunomodulatory potential.

Holistic approaches to HIV care aim to improve the lives of people living with HIV (PLWH) by shifting focus toward health systems that are more people-orientated and less disease-orientated. Social prescribing is one such approach that refers individuals to co-design non-clinical social prescriptions to improve their health and well-being. This qualitative study aimed to explore PLWH and support personnel preferences for the content and delivery of a socially prescribed psychoeducation model for PLWH in Ireland. Individual interviews were conducted with five PLWH and eight support personnel. Content analysis identified six superordinate categories with thirteen subcategories, identifying opportunities to empower PLWH through shared decision-making with trusted service providers and improved access to community resources, potential for peer support to combat social isolation and improve well-being, methods to overcome barriers to participation and improve cultural competency, and rationale to promote integrated social support that promotes a multidisciplinary approach and continuum of care.

People living with HIV (PLWH) face unique biopsychosocial challenges due to both infection and antiretroviral therapy (ART), one of which is body image disruption. This study comprehensively reviewed relevant studies to explore body image issues, identify associated factors, and describe assessment methods and interventions targeting body image in this population. Guided by the PRISMA, a thorough search of PsycINFO, PubMed, Embase, and Web of Science was conducted in November 2024, using search terms relevant to HIV and Body image. NIH Study Quality Assessment Tools were used to assess the quality of the included studies, and a narrative synthesis was conducted to identify common themes, including definitions of body image, associated factors, measurement instruments, and interventions targeting body image among PLWH. From 2197 publications, 26 studies met the inclusion criteria. The majority of studies demonstrated an association between negative body image and psychosocial factors, including depression, anxiety, social withdrawal, and substance use. Body image dissatisfaction was also associated with physical health factors such as lipodystrophy. Sixteen distinct body image measurement tools were used across studies. Cognitive Behavioral Therapy for Body Image and Self-Care (CBT-BISC) was the only target intervention that showed effectiveness in mitigating body image disturbance and improving ART adherence among PLWH. This is the first comprehensive scoping review to exclusively consider body image, associated factors, measurements, and target interventions among PLWH, which highlighted the need for comprehensive, culturally sensitive interventions that address both the physical and psychological dimensions of body image concerns.

BackgroundThis study aimed to identify people living with HIV (PLWH) with tuberculosis (TB) co-infection, explore their demographic and clinical characteristics, and determine predictors of early mortality within 6months of TB diagnosis.MethodsA cross-sectional study was conducted in a tertiary referral center in Türkiye of PLWH diagnosed with TB between 2004 and 2023. Demographic, clinical, and laboratory data were reviewed, and statistical analyses were performed to identify early mortality predictors.ResultsAmong 1541 PLWH, 62 (4%) had TB, and 23 (37%) died within 6months. TB presentations were pulmonary (44%), extrapulmonary (27%), and both (29%). Predictors significantly associated with early mortality included lymphopenia (p = 0.009), a CD4 + T lymphocyte count ≤50 cells/mm3 (p = 0.015), anemia (p = 0.009), and thrombocytopenia (p = 0.034), particularly platelet counts below 150,000/mm3 (p = 0.001). Clinical predictors also included symptoms such as fever (p = 0.017), anorexia (p = 0.012), weight loss (p = 0.012), and altered mental status (p = 0.043). Additionally, receiver operating characteristic (ROC) analysis demonstrated that CD4 + T lymphocyte count ≤50 cells/mm3 (AUC = 0.76, p = 0.039) and platelet count <150,000/mm3 (AUC = 0.71, p = 0.034) were significant predictive cutoffs for early mortality. TB culture positivity was high (84%), while PCR positivity was low (15%). Opportunistic infections were seen in 11% of cases.ConclusionsHigh early mortality among people living with HIV/TB co-infection is associated with advanced immunosuppression and hematological abnormalities. These results highlight the importance of early HIV detection and close clinical monitoring to reduce mortality.

This study investigated the effects of subjective health status and grit (a personality trait) on subjective cognitive decline (SCD) in adult people living with HIV (PLWH) in Nigeria, as previous research suggested that these factors may predict cognitive functioning. A total of 150 PLWH (Mage = 55.19) completed paper-based questionnaires at a teaching hospital in Nigeria. Multiple linear regression showed that better subjective health status was negatively associated with SCD. Grit-components (consistency of interest and perseverance of effort) moderated the association between subjective health and SCD. Higher consistency of interest strengthened the protective effect of positive subjective health on SCD, while low perseverance of effort amplified this protective association. The role of personality traits on health and cognitive decline in adults living with HIV in Nigeria warrants more studies to help inform cognitive health intervention programs for middle-aged and older adults with HIV.

Virus-induced accelerated aging has emerged as a potential contributor to HIV-associated neurocognitive disorders (HAND), despite widespread implementation of combination antiretroviral therapy (cART). Although evidence of accelerated aging in people living with HIV (PLWH) has been reported, most investigations of acute infection rely on in vitro systems or small animal models, leaving a critical gap in understanding early neuropathological events. To address this, we analyzed formalin-fixed, paraffin-embedded (FFPE) brain tissues from rhesus macaques acutely infected with simian immunodeficiency virus (SIV). We focused on two key aging-related proteins: the cellular senescence marker p16 INK4a (p16) and the NAD-dependent deacetylase sirtuin 1 (SIRT1). We hypothesized that accelerated aging phenotypes would be detectable during acute infection, manifesting as increased p16 expression and altered SIRT1 levels, correlating with neurodegeneration. Consistent with this hypothesis, we observed marked upregulation of GFAP and p16, along with evidence of neurodegeneration, across multiple brain regions - including the frontal lobe, caudate, putamen, thalamus, hippocampus, and cerebellum - by 21 days post-infection. These findings suggest that aging-related and senescence pathways are activated almost immediately following HIV infection, highlighting the potential importance of astrocyte- or CNS-specific therapeutic strategies to mitigate early neuropathology.