An essential role for the IL-2 receptor in Treg cell function.

Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+ T cells but was important for limiting the activation of CD8+ T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Treg cells separable from signaling via the T cell antigen receptor.

Continuous requirement for the TCR in regulatory T cell function.

Foxp3(+) regulatory T cells (T(reg) cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of T(reg) cells, the role of TCR signaling in T(reg) cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in T(reg) cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of T(reg) cell signature genes or altered ability to sense and consume interleukin 2 (IL-2). Instead, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated T(reg) cell transcriptional signature. Our results reveal a critical role for the TCR in the suppressor capacity of T(reg) cells.

The relationship between synaptodendritic neuropathology and HIV-associated neurocognitive disorders is moderated by cognitive reserve.

We examined whether cognitive reserve moderated the relationship between neurodegeneration and cognition in 67 postmortem persons with HIV (PWH) who were cognitively assessed within 1 year of death. Cognitive reserve was measured via the Wide Range Achievement Test-4 reading subtest (WRAT4). Synaptodendritic neurodegeneration was based on densities of synaptophysin and microtubule-associated protein 2 immunohistochemical reactivity in frontal cortex, and categorized as minimal, moderate, or severe (tertile-split). T-Scores from 15 cognitive tests were averaged into a global cognitive T-score. Among those with low cognitive reserve (based on WRAT4 median split), the moderate neurodegeneration group showed cognition that was poorer than the minimal neurodegeneration group and comparable to the severe neurodegeneration group. Among those with high cognitive reserve, the moderate neurodegeneration group showed cognition comparable to the minimal neurodegeneration group and better than the severe neurodegeneration group. High cognitive reserve may buffer against cognitive impairment among PWH with moderate, but not severe, neurodegeneration.

Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents.

We have previously shown accelerated ageing in adolescents perinatally infected with HIV (PHIV +), based on discrepancies between epigenetic and chronological age. The current study examines follow-up longitudinal patterns of epigenetic ageing and the association of epigenetic ageing with cognition as well as whole brain structure changes in PHIV + and healthy controls enrolled in the Cape Town Adolescent Antiretroviral Cohort Study (CTAAC). The Illumina EPIC array was used to generate blood DNA methylation data from 60 PHIV + adolescents and 36 age-matched controls aged 9-12 years old at baseline and again at a 36-month follow-up. Epigenetic clock software estimated two measures of epigenetic age acceleration: extrinsic epigenetic accelerated ageing (EEAA) and age acceleration difference (AAD) at both time points. At follow-up, each participant completed neuropsychological testing, structural magnetic resonance imaging, and diffusion tensor imaging. At follow-up, PHIV infection remains associated with increased EEAA and AAD. Accelerated epigenetic ageing remained positively associated with viral load and negatively associated with CD4 ratio. EEAA was positively associated with whole brain grey matter volume and alterations in whole brain white matter integrity. AAD and EEAA were not associated with cognitive function within the PHIV + group. Measures of epigenetic ageing, as detected in DNA methylation patterns, remain increased in PHIV + adolescents across a 36-month period. Associations between epigenetic ageing measures, viral biomarkers, and alterations in brain micro- and macrostructure also persist at 36-month follow-up. Further study should determine if epigenetic age acceleration is associated with cognitive functional changes due to brain alterations in later life.

Corrigendum: Stability and function of regulatory T cells expressing the transcription factor T-bet.

This corrects the article DOI: 10.1038/nature22360.

Stability and function of regulatory T cells expressing the transcription factor T-bet.

Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity. Whether expression of these factors in Treg cells-as in effector T cells-is indicative of heterogeneity of functionally discrete and stable differentiation states, or conversely may be readily reversible, is unknown. Here we demonstrate that expression of the TH1-associated transcription factor T-bet in mouse Treg cells, induced at steady state and following infection, gradually becomes highly stable even under non-permissive conditions. Loss of function or elimination of T-bet-expressing Treg cells-but not of T-bet expression in Treg cells-resulted in severe TH1 autoimmunity. Conversely, following depletion of T-bet- Treg cells, the remaining T-bet+ cells specifically inhibited TH1 and CD8 T cell activation consistent with their co-localization with T-bet+ effector T cells. These results suggest that T-bet+ Treg cells have an essential immunosuppressive function and indicate that Treg cell functional heterogeneity is a critical feature of immunological tolerance.

Progress toward gender equality in the United States has slowed or stalled.

We examine change in multiple indicators of gender inequality for the period of 1970 to 2018. The percentage of women (age 25 to 54) who are employed rose continuously until ∼2000 when it reached its highest point to date of 75%; it was slightly lower at 73% in 2018. Women have surpassed men in receipt of baccalaureate and doctoral degrees. The degree of segregation of fields of study declined dramatically in the 1970s and 1980s, but little since then. The desegregation of occupations continues but has slowed its pace. Examining the hourly pay of those aged 25 to 54 who are employed full-time, we found that the ratio of women's to men's pay increased from 0.61 to 0.83 between 1970 and 2018, rising especially fast in the 1980s, but much slower since 1990. In sum, there has been dramatic progress in movement toward gender equality, but, in recent decades, change has slowed and on some indicators stalled entirely.

Consumer? Views and preferences of people receiving public mental health care in Australia on the terms used to refer to them.

OBJECTIVES: To understand: a) whether adults receiving public mental health care were aware they were officially referred to as 'consumers' and, b) their views and preferences on the terms used to refer to them. METHODS: Single-page, anonymous survey conducted across two community mental health services in Northern New South Wales (NNSW). Ethics approval obtained from the local research office. RESULTS: 108 people completed the survey with a response rate of approximately 22%. The vast majority (77%) of respondents were not aware that they were officially referred to as 'consumers'. 32% of respondents disliked the term 'consumer' and 11% found it offensive. Half preferred the term 'patient', particularly when consulting a psychiatrist (55%). A small minority (5-7%) preferred the term 'consumer' for any care interaction. CONCLUSION: Most respondents in this survey wished to be referred to as a 'patient' and a large proportion disliked being referred to as a 'consumer' or found it offensive. Further surveys should include broader sociodemographic and diagnostic/treatment variables. Official terms used to refer to people receiving public mental health care should be person-centred and evidence based.

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .

Sexualities and Geographic Mobility Between Childhood and Adulthood in the United States.

Though research suggests that sexual minorities (e.g., nonheterosexual individuals) are more geographically mobile in the transition to adulthood than their heterosexual counterparts, quantitative estimates are rare and previously used data sources have significant limitations. Using data from the National Longitudinal Study of Adolescent to Adult Health (N = 11,705) that directly measure sexualities across dimensions (i.e., identity, behavior, and attraction), I examine variation in geographic mobility between childhood (ages 11-17) and adulthood (ages 26-34) across various sexualities (e.g., gay/lesbian and bisexual). Three findings emerge. First, mobility varies across sexualities. Individuals with gay/lesbian identity, same-sex behavior, and same-sex attraction are more geographically mobile than individuals with heterosexual identity, different-sex behavior, and different-sex attraction, respectively. By contrast, individuals with bisexual identity, both-sex behavior, and both-sex attraction tend to be statistically indistinct from individuals with heterosexual identity, different-sex behavior, and different-sex attraction, respectively. Second, mobility differences are largest and most prevalent when sexualities are operationalized according to identity. Third, evidence suggests that the effects of gay/lesbian identity, same-sex behavior, and same-sex attraction on mobility are larger for men than for women. In providing the first quantitative estimates of geographic mobility differences across broader sexual minority and heterosexual populations, this study expands inquiry related to sexualities and mobility.

Magnitude and Kinetics of Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. METHODS: Sera (n = 533) from patients with real-time polymerase chain reaction-confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. RESULTS: Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. CONCLUSIONS: High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

Longitudinal multivariate normative comparisons.

Motivated by the Multicenter AIDS Cohort Study (MACS), we develop classification procedures for cognitive impairment based on longitudinal measures. To control family-wise error, we adapt the cross-sectional multivariate normative comparisons (MNC) method to the longitudinal setting. The cross-sectional MNC was proposed to control family-wise error by measuring the distance between multiple domain scores of a participant and the norms of healthy controls and specifically accounting for intercorrelations among all domain scores. However, in a longitudinal setting where domain scores are recorded multiple times, applying the cross-sectional MNC at each visit will still have inflated family-wise error rate due to multiple testing over repeated visits. Thus, we propose longitudinal MNC procedures that are constructed based on multivariate mixed effects models. A χ2 test procedure is adapted from the cross-sectional MNC to classify impairment on longitudinal multivariate normal data. Meanwhile, a permutation procedure is proposed to handle skewed data. Through simulations we show that our methods can effectively control family-wise error at a predetermined level. A dataset from a neuropsychological substudy of the MACS is used to illustrate the applications of our proposed classification procedures.

Immune homeostasis enforced by co-localized effector and regulatory T cells.

FOXP3(+) regulatory T cells (Treg cells) prevent autoimmunity by limiting the effector activity of T cells that have escaped thymic negative selection or peripheral inactivation. Despite the information available about molecular factors mediating the suppressive function of Treg cells, the relevant cellular events in intact tissues remain largely unexplored, and whether Treg cells prevent activation of self-specific T cells or primarily limit damage from such cells has not been determined. Here we use multiplex, quantitative imaging in mice to show that, within secondary lymphoid tissues, highly suppressive Treg cells expressing phosphorylated STAT5 exist in discrete clusters with rare IL-2-positive T cells that are activated by self-antigens. This local IL-2 induction of STAT5 phosphorylation in Treg cells is part of a feedback circuit that limits further autoimmune responses. Inducible ablation of T cell receptor expression by Treg cells reduces their regulatory capacity and disrupts their localization in clusters, resulting in uncontrolled effector T cell responses. Our data thus reveal that autoreactive T cells are activated to cytokine production on a regular basis, with physically co-clustering T cell receptor-stimulated Treg cells responding in a negative feedback manner to suppress incipient autoimmunity and maintain immune homeostasis.

Multilevel Factors Shaping Awareness of and Attitudes Toward Pre-exposure Prophylaxis for HIV Prevention among Criminal Justice-Involved Women.

Although pre-exposure prophylaxis (PrEP) is a key tool in HIV prevention efforts, little is known about PrEP as a prevention strategy for criminal justice-involved (CJI) women. The purpose of this study was to examine multilevel factors shaping PrEP awareness and acceptability among CJI women. Between January 2017 and December 2017, we conducted 52 interviews with CJI women at high risk for HIV and stakeholders from the criminal justice (CJ) and public health (PH) systems. Interviews explored awareness of PrEP and the multilevel factors shaping PrEP acceptability. Data were analyzed using inductive thematic analysis and executive summaries. Atlas.ti facilitated analyses. The majority of CJI women (n = 27) were, on average, 41.3 years, from racial and ethnic minority groups (56% Black/African-American; 19% Latinx) and reported engaging in recent high-risk behavior (nearly 60% engaged in transactional sex, 22% reported ≥ 4 sexual partners, and 37% reported injection drug use). Of system stakeholders (n = 25), 52% represented the CJ sector. Although CJI women were generally unaware of PrEP, attitudes toward PrEP were enthusiastic. Barriers to PrEP acceptability included medication side effects (individual level); distrust in HIV prevention mechanisms (community level); lack of local HIV prevention efforts among high-risk women (public policy/HIV epidemic stage level). Factors promoting PrEP included perceived HIV risk (individual level); PrEP being an HIV prevention method that women can control without partner negotiation (social and sexual network level); and availability of public health insurance (community level). Despite low awareness of PrEP, CJI women expressed positive attitudes toward PrEP. To improve PrEP access for CJI women, implementation efforts should address barriers and leverage facilitators across multiple levels to be maximally effective.

Studying the neuropsychological sequelae of SARS-CoV-2: lessons learned from 35 years of neuroHIV research.

The virology of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the human immune response to the virus are under vigorous investigation. There are now several reports describing neurological symptoms in individuals who develop coronavirus disease 2019 (COVID-19), the syndrome associated with SARS-CoV-2 infection. The prevalence, incidence, and clinical course of these symptoms will become clearer in the coming months and years through epidemiological studies. However, the long-term neurological and cognitive consequence of SARS-CoV-2 infection will remain conjectural for some time and will likely require the creation of cohort studies that include uninfected individuals. Considering the early evidence for neurological involvement in COVID-19 it may prove helpful to compare SARS-CoV-2 with another endemic and neurovirulent virus, human immunodeficiency virus-1 (HIV-1), when designing such cohort studies and when making predictions about neuropsychological outcomes. In this paper, similarities and differences between SARS-CoV-2 and HIV-1 are reviewed, including routes of neuroinvasion, putative mechanisms of neurovirulence, and factors involved in possible long-term neuropsychological sequelae. Application of the knowledge gained from over three decades of neuroHIV research is discussed, with a focus on alerting researchers and clinicians to the challenges in determining the cause of neurocognitive deficits among long-term survivors.

A candidate gene study of intermediate histopathological phenotypes in HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) describe a spectrum of neuropsychological impairment caused by HIV-1 infection. While the sequence of cellular and physiological events that lead to HAND remains obscure, it likely involves chronic neuroinflammation. Host genetic markers that increase the risk for HAND have been reported, but replication of such studies is lacking, possibly due to inconsistent application of a behavioral phenotype across studies. In the current study, we used histopathologic phenotypes in order to validate putative risk alleles for HAND. The National NeuroAIDS Tissue Consortium, a longitudinal study of the neurologic manifestations of HIV. Data and specimens were obtained from 175 HIV-infected adults. After determining several potential covariates of neurocognitive functioning, we quantified levels of six histopathological markers in the frontal lobe in association with neurocognitive functioning: SYP, MAP 2, HLA-DR, Iba1, GFAP, and ß-amyloid. We then determined alleles of 15 candidate genes for their associations with neurocognitive functioning and histopathological markers. Finally, we identified the most plausible causal pathway based on our data using a multi-stage linear regression-based mediation analysis approach. None of the genetic markers were associated with neurocognitive functioning. Of the histopathological markers, only MAP 2 and SYP were associated with neurocognitive functioning; however, MAP 2 and SYP did not vary as a function of genotype. Mediation analysis suggests a causal pathway in which presynaptic degeneration (SYP) leads to somatodendritic degeneration (MAP 2) and ultimately neurocognitive impairment. This study did not support the role of host genotype in the histopathology underlying HAND. The findings lend further support for synaptodendritic degeneration as the proximal underlying neuropathological substrate of HAND.

Correction to: A candidate gene study of intermediate histopathological phenotypes in HIV-associated neurocognitive disorders.

Due to a production error data in Table 1 were not presented correctly.

Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

Associations of regional amyloid-ß plaque and phospho-tau pathology with biological factors and neuropsychological functioning among HIV-infected adults.

With increasing age, the general population is increasingly vulnerable to the development of cerebral amyloid-ß (Aß) plaque and neuronal phospho-tau (p-tau) pathology. In HIV disease, prior studies of these neuropathologic changes were relatively limited. Here, we characterized Aß plaques and p-tau lesions by immunohistochemistry in relevant brain regions (prefrontal neocortex, putamen, basal-temporal neocortex, and hippocampus) of HIV-infected adults. We used multivariable logistic regression to predict regional Aß plaque or p-tau pathology based on demographic factors, apolipoprotein E (APOE) genotypes, HIV disease-related factors, and regional gliosis. We used multiple linear regression to predict T-scores in neuropsychological domains based on regional Aß plaque or p-tau pathology. We found that APOE ε4 alleles, older age, and higher plasma HIV-1 RNA predicted prefrontal Aß plaques (odds ratio (OR) 5.306, 1.045, and 0.699, respectively, n = 168). Older age predicted putamen Aß plaques (OR 1.064, n = 171). APOE ε4 alleles, hepatitis C virus seropositivity, and higher plasma HIV-1 RNA predicted hippocampus Aß plaques (OR 6.779, 6.138, and 0.589, respectively, n = 56). The p-tau lesions were sparse in the vast majority of affected cases. Lifetime substance use disorder and higher plasma HIV-1 RNA predicted putamen p-tau lesions (OR 0.278 and 0.638, respectively, n = 67). Older age and gliosis predicted hippocampus p-tau lesions (OR 1.128 and 0.592, respectively, n = 59). Prefrontal Aß plaques predicted lower speed of information processing (n = 159) and putamen Aß plaques predicted lower levels of attention and working memory (n = 88). Regional p-tau lesions were not significantly predictive of any neuropsychological domains. In conclusion, Aß plaque or p-tau pathology in different brain regions was predicted by different sets of biological factors. Aß plaques in prefrontal neocortex and putamen predicted poorer functioning in cognitive domains relevant to these brain regions. The absence of significant impact of regional p-tau lesions on neuropsychological functioning might be explained by the subthreshold burden of p-tau lesions.

Inflammation-related genes are associated with epigenetic aging in HIV.

Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.