Study design features that improve effect sizes in cross-sectional and longitudinal brain-wide association studies.

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behavior associations. Several recent studies showed that thousands of study participants are required to improve the replicability of BWAS because actual effect sizes are much smaller than those reported in smaller studies. Here, we perform analyses and meta-analyses of a robust effect size index (RESI) using 63 longitudinal and cross-sectional magnetic resonance imaging studies from the Lifespan Brain Chart Consortium (77,695 total scans) to demonstrate that optimizing study design is critical for improving standardized effect sizes and replicability in BWAS. A meta-analysis of brain volume associations with age indicates that BWAS with larger covariate variance have larger effect size estimates and that the longitudinal studies we examined have systematically larger standardized effect sizes than cross-sectional studies. We propose a cross-sectional RESI to adjust for the systematic difference in effect sizes between cross-sectional and longitudinal studies that allows investigators to quantify the benefit of conducting their study longitudinally. Analyzing age effects on global and regional brain measures from the United Kingdom Biobank and the Alzheimer's Disease Neuroimaging Initiative, we show that modifying longitudinal study design through sampling schemes to increase between-subject variability and adding a single additional longitudinal measurement per subject can improve effect sizes. However, evaluating these longitudinal sampling schemes on cognitive, psychopathology, and demographic associations with structural and functional brain outcome measures in the Adolescent Brain and Cognitive Development dataset shows that commonly used longitudinal models can, counterintuitively, reduce effect sizes. We demonstrate that the benefit of conducting longitudinal studies depends on the strengths of the between- and within-subject associations of the brain and non-brain measures. Explicitly modeling between- and within-subject effects avoids conflating the effects and allows optimizing effect sizes for them separately. These findings underscore the importance of considering study design features to improve the replicability of BWAS.

An uncommon presentation of a multifocal spinal osseous sarcoidosis: A case report on the diagnosis and exclusion with literature review.

Sarcoidosis is a granulomatous disease of indeterminate etiology. Women are more commonly affected than men at nearly twice the incidence with black women most commonly afflicted in the United States. Osseous spinal sarcoidosis (SS) is thought to be uncommon. Such lesions are often mistaken for metastatic disease, multiple myeloma, or disseminated fungal/granulomatous infection complicating the diagnosis, clinical course, and treatment. Patients presenting with clinical and imaging features of sarcoidosis may have normal serum laboratory values further complicating diagnosis. We present the case of a 61-year-old African American female with a diagnosis of osseous spinal sarcoidosis and normal calcium and ACE levels. Her initial presentation began with an incidentally discovered pulmonary nodule and was subsequently discovered to have multiple enlarging pulmonary nodules and widespread sclerotic lesions throughout her spine. This imaging presentation occurred before development of hilar adenopathy and cutaneous manifestations of sarcoidosis. Here, we describe her clinical course, exclusion of metastatic disease, and other confounders to arrive at the correct diagnosis.

XCP-D: A Robust Pipeline for the post-processing of fMRI data.

Functional neuroimaging is an essential tool for neuroscience research. Pre-processing pipelines produce standardized, minimally pre-processed data to support a range of potential analyses. However, post-processing is not similarly standardized. While several options for post-processing exist, they tend not to support output from disparate pre-processing pipelines, may have limited documentation, and may not follow BIDS best practices. Here we present XCP-D, which presents a solution to these issues. XCP-D is a collaborative effort between PennLINC at the University of Pennsylvania and the DCAN lab at the University at Minnesota. XCP-D uses an open development model on GitHub and incorporates continuous integration testing; it is distributed as a Docker container or Singularity image. XCP-D generates denoised BOLD images and functional derivatives from resting-state data in either NifTI or CIFTI files, following pre-processing with fMRIPrep, HCP, and ABCD-BIDS pipelines. Even prior to its official release, XCP-D has been downloaded >3,000 times from DockerHub. Together, XCP-D facilitates robust, scalable, and reproducible post-processing of fMRI data.

Corrigendum: Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response.

[This corrects the article DOI: 10.3389/fimmu.2020.00053.].

Cross sectional analysis of the effect of alcohol on pulmonary function in a cohort of men and women living with HIV.

People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease in part due to opportunistic infections including pneumonia. HIV infection is associated with increased prevalence of impaired lung function and abnormal gas exchange. Alcohol use disorder (AUD) is exceedingly common in PLWH and is associated with higher risk of pneumonia in PLWH. Alcohol use may lead to lung damage through several mechanisms. Data on the long-term effect of AUD on pulmonary function in PLWH are sparse and conflicting. To evaluate this relationship, we conducted a cross-sectional analysis of adult PLWH in care in Louisiana. We hypothesized that chronic alcohol use would be associated with subsequent pulmonary dysfunction in a dose-dependent fashion. All participants performed standardized spirometry on study entry. In total, 350 participants with acceptable spirometry were included in this analysis. Thirty-one percent of participants were female. Women reported less lifetime alcohol use and less smoking; however, they reported more chronic respiratory symptoms. In adjusted models, total lifetime alcohol use was not associated with spirometry measures of pulmonary function. HIV-related variables (CD4 count and viral load) were also not associated with measures of pulmonary function. We then conducted sex-stratified analyses to eliminate residual confounding of sex and similarly found no association of total lifetime alcohol use and pulmonary function. We found no association of AUDIT score or early life alcohol use and pulmonary function. In latent class factor analysis, current heavy alcohol use was associated with lower measures of pulmonary function as compared to former heavy alcohol use. In summary, in this cohort of New Orleanian men and women living with HIV with robust measures of alcohol use, though total lifetime alcohol use and early life alcohol use were not associated with pulmonary function, current heavy alcohol use was associated with impaired pulmonary function.

Antiretroviral therapy administration reduces neuroinflammation without restoring brain-derived neurotrophic factor signaling in alcohol-administered simian immunodeficiency virus-infected macaques.

OBJECTIVE: The present study examined interactions between simian immunodeficiency virus (SIV), chronic binge alcohol (CBA), and antiretroviral therapy (ART) on growth factor signaling, neuroinflammatory markers, viral loads (VL), and CD4+ cell counts. DESIGN: Adult male rhesus macaques were administered CBA (13-14 g ethanol (EtOH)/kg per week) or sucrose (SUC) 3 months prior to SIVmac251 infection until the study endpoint. At viral setpoint, a subset of CBA/SIV+ and SUC/SIV+ macaques were randomized to receive daily ART (9-[2-Phosphonyl-methoxypropyly]adenine [PMPA] 20 mg/kg, 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC), 30 mg/kg). Frontal cortex (FC) and basal ganglia (BG) were collected for gene and protein expression. METHODS: Relationships between brain and plasma VL or CD4+ cell counts were determined using linear regression. Effects of SIV, CBA, and ART on markers of neuroinflammation and brain-derived neurotrophic factor (BDNF) signaling were determined by ANOVA and linear regression. RESULTS: SIV increased FC and BG neuroinflammatory and glial cell gene expression (CX3CR1, B2M), and reduced FC protein kinase B phosphorylation. CBA decreased FC and BG tropomyosin receptor kinase B (TrkB) phosphorylation, and increased full-length TrkB (TrkB-FL) and SLC1A3 expression in FC and BG, respectively. ART suppressed plasma and brain VL, reduced neuroinflammatory gene expression in FC (IBA1, CX3CR1, and GFAP), and BG (CD74 and CD11ß), and did not restore FC or BG BDNF signaling deficits. CONCLUSIONS: Results show ART-mediated reduction in VL and neuroinflammatory gene expression, irrespective of CBA administration. ART did not attenuate SIV- and CBA-mediated BDNF signaling deficits, suggesting these deficits, despite effective neuroinflammation suppression, may explain CBA- and SIV-associated neurocognitive deficits. Therapeutics targeting growth factor signaling may be important adjuvants in treating HIV-associated neurocognitive decline.

Slow-growing lesion on eyebrow.

It took a dermatoscopic examination followed by an e-consultation and shave biopsy to arrive at the diagnosis.

Diffuse skeletal muscle extramedullary plasmacytomas: a rare case and review of the literature.

Extramedullary plasmacytomas are rare neoplasms arising from proliferations of monoclonal plasma cells. In primary form, these malignancies occur without other sites of plasma cell disease. Secondary extramedullary plasmacytomas occur in association with multiple myeloma and may be discovered during initial intramedullary disease or may occur during multiple myeloma relapse. In very rare instances, secondary extramedullary plasmacytomas have multifocal skeletal muscle involvement. We present a case of multifocal skeletal muscle plasmacytomas in a 58-year-old man with shoulder-reduced range of motion, pain, and a history of previously treated multiple myeloma. To our knowledge, the patient's unique relapse presentation of torso and shoulder soft tissue masses and the vast extent of skeletal muscle involvement are unique to cases in the current literature. This case also has MRI findings of a muscular plasmacytoma with internal hemorrhage which has not been previously reported. This case report will review imaging features and clinical presentations of intramuscular extramedullary plasmacytomas. Since imaging surveillance for multiple myeloma relapse is commonly performed, radiologists should be aware of these uncommon relapsing features including multifocal intramuscular masses which may contain internal hemorrhage.

Comprehensive Assessment of Alcohol Consumption in People Living with HIV (PLWH): The New Orleans Alcohol Use in HIV Study.

BACKGROUND: High frequency of alcohol use among people living with HIV (PLWH) warrants careful assessment and screening to better understand its impact on HIV disease progression and development of comorbidities. Due to the limitations of the tools used to measure alcohol use, the links to health consequences are not fully understood. METHODS: We completed a cross-sectional analysis to examine the prevalence of alcohol consumption using multiple alcohol assessment tools and their correlation and consistency in a cohort of PLWH (N = 365) enrolled in the New Orleans Alcohol Use in HIV (NOAH) Study. Alcohol use was assessed with the Alcohol Use Disorders Identification Test (AUDIT), timeline followback (TLFB) Calendar, lifetime drinking history, Alcohol and Drug Addiction Severity Index, and blood levels of phosphatidylethanol (PEth). Spearman's correlations were estimated for continuous measures of alcohol consumption; Wilcoxon rank-sum tests were used to compare means; and logistic regression was used to estimate odds of alcohol use by demographic characteristics. RESULTS: Self-report of current alcohol use varied from 58.9 to 73.7% depending on the assessment. All the self-reported alcohol measures showed statistically significant correlations with the biological marker PEth. The highest correlation was with TLFB grams (r = 0.67, p < 0.001). Using TLFB, 73.7% of the cohort reported using alcohol in the last 30 days, and 61.6% had a positive PEth value. The prevalence of risky drinkers, meeting the TLFB > 3 (women) or >4 (men) drinks/day or>7 (women) or>14 (men) drinks/week, was 49.0%. Medium-risk drinking defined as an AUDIT score ≥ 8 was reported in 40.3%, and high-risk drinkers/probable AUD (AUDIT score ≥ 16) was met by 17.0% of the cohort. CONCLUSIONS: Our results demonstrate the importance of comprehensive assessments for alcohol use, including self-report via multiple assessment tools administered by trained staff, as well as the addition of biomarkers for improved classification of subjects into different drinking categories.

Short-Chain Alcohols Upregulate GILZ Gene Expression and Attenuate LPS-Induced Septic Immune Response.

Alcohol differentially affects human health, depending on the pattern of exposure. Moderate intake provides beneficial mood modulation and an anti-inflammatory effect, while excessive consumption leads to immunosuppression and various alcohol use disorders. The mechanism underlying this bi-phasic action mode of alcohol has not been clearly defined. Our previous publication demonstrated that ethanol, in the absence of glucocorticoids (GCs), induces expression of Glucocorticoid-Induced Leucine Zipper (GILZ), a key molecule that transduces GC anti-inflammatory effect through a non-canonical activation of glucocorticoid receptor (1). Here we report that similar short-chain alcohols, such as ethanol, propanol and isopropanol, share the same property of upregulating GILZ gene expression, and blunt cell inflammatory response in vitro. When mice were exposed to these alcohols, GILZ gene expression in immune cells was augmented in a dose-dependent manner. Monocytes and neutrophils were most affected. The short-chain alcohols suppressed host inflammatory response to lipopolysaccharide (LPS) and significantly reduced LPS-induced mortality. Intriguingly, propanol and isopropanol displayed more potent protection than ethanol at the same dose. Inhibition of ethanol metabolism enhanced the ethanol protective effect, suggesting that it is ethanol, not its derivatives or metabolites, that induces immune suppression. Taken together, short-chain alcohols per se upregulate GILZ gene expression and provide immune protection against LPS toxicity, suggesting a potential measure to counter LPS septic shock in a resource limited situation.

Ultrasound Fatty Liver Indicator: A Simple Tool for Differentiating Steatosis From Nonalcoholic Steatohepatitis: Validity in the Average Obese Population.

OBJECTIVES: Steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis/cirrhosis represent a spectrum of fatty liver disease. The ultrasound fatty liver indicator (US-FLI) evaluates ultrasound (US) features to identify stages of fatty liver disease. We hypothesized that US features could be independent predictors of NASH and that the US-FLI differentiates steatosis from NASH in the average obese population. METHODS: A retrospective analysis of 208 patients with normal (n = 14), steatotic (n = 89), and NASH (n = 105) livers was performed. Liver/biliary disease and a history of alcohol intake were excluded. Ultrasound metrics included liver-kidney contrast, posterior attenuation, vessel blurring, difficulty visualizing the gallbladder wall, difficulty visualizing the diaphragm, and areas of focal fatty sparing. A statistical comparison of the 3 groups as well as fibrosis stage I and II/III NASH groups was performed. Logistic regression identified independent predictors of NASH. RESULTS: Gallbladder wall visualization and vessel blurring were different between the steatosis and NASH groups (P ≤ .01). Gallbladder wall visualization was specific for NASH (89%), and vessel blurring was sensitive for NASH (93%). A US-FLI score of 4 or lower suggested the absence of NASH (negative predictive value, 88%; sensitivity, 91%). Logistic regression revealed vessel blurring as the only US predictor of NASH (P ≤ .01). However, the area under the curve (0.649) showed poor performance in differentiating steatosis from NASH when the US-FLI score was 5 or higher. CONCLUSIONS: Our data suggest that the US-FLI may differentiate steatosis from NASH in the average obese population. Vessel blurring and poor gallbladder wall visualization were the most important metrics. Identification of NASH was enhanced by including the US-FLI score with vessel blurring.

Chronic Binge Alcohol-Associated Differential Brain Region Modulation of Growth Factor Signaling Pathways and Neuroinflammation in Simian Immunodeficiency Virus-Infected Male Macaques.

AIMS: Microarray analysis of hippocampal tissue from chronic binge alcohol (CBA)-administered, simian immunodeficiency virus (SIV)-infected male macaques identified altered immune response and neurogenesis as potential mechanisms underlying cognitive deficits in macaques. This study investigated the differential brain region associations between markers of neuroinflammation and growth factor signaling with microtubule-associated protein 2 (MAP2) expression. METHODS: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week, n = 8) or sucrose (SUC, n = 7) beginning 3 months prior to SIV infection and continued until animals reached end-stage disease criteria (3-24 months post infection). Expression of inflammatory cytokines, growth factors, and viral loads were determined in the prefrontal cortex (PFC), caudate (CD), and hippocampus (HP). Brain-derived neurotropic factor (BDNF) expression and phosphorylation of intracellular kinases downstream of BDNF were investigated in the PFC. RESULTS: Our results show reduced MAP2 expression in the PFC of longer-surviving, CBA/SIV macaques. BDNF expression was most closely associated with MAP2 expression in the PFC. In the caudate, significant positive associations were observed between MAP2 and BDNF, time to end-stage and set-point viral load and significant negative associations for CBA. In the hippocampus, positive associations were observed between MAP2 and inflammatory cytokines, and negative associations for brain viral load and CBA. CONCLUSIONS: CBA differentially affects growth factor and inflammatory cytokine expression and viral load across brain regions. In the PFC, suppression of growth factor signaling may be an important neuropathological mechanism, while inflammatory processes may play a more important role in the CD and HP.

The New Orleans Alcohol Use in HIV Study: Launching a Translational Investigation of the Interaction of Alcohol Use with Biological and Socioenvironmental Risk Factors for Multimorbidity in People Living with HIV.

BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in people living with HIV (PLWH) and are associated with increased HIV risk behaviors, suboptimal treatment adherence, potential interaction with medication pharmacodynamics, and greater risk for disease progression. Preclinical studies show that chronic binge alcohol administration accelerates disease progression and aggravates pathogenesis in the simian immunodeficiency virus (SIV)-infected rhesus macaque model despite viral suppression by antiretroviral therapy. METHODS: To translate preclinical findings in the rhesus macaque model of chronic binge alcohol administration and SIV infection and to address areas of uncertainty surrounding the biological mechanisms and socioenvironmental modifiers that contribute to the relationship between alcohol use and HIV-associated comorbidities, precocious aging, and disease progression, we designed a translational multiproject, longitudinal, cohort study, and the New Orleans Alcohol Use in HIV (NOAH) Study. The NOAH Study is led by a multidisciplinary team of scientists, with a research focus on the interaction of AUD and HIV. The overarching hypothesis is that alcohol use will lead to adverse health outcomes in PLWH. In this report, we describe the study design and baseline descriptive characteristics of our cohort. RESULTS: Three-hundred and sixty-five participants completed the baseline testing. The cohort is predominantly male (69%) and African American (83.5%). The majority of participants report incomes below 200% of the federal poverty level. CD4 counts <200 cells/µl were found in 12.8% and viral loads <50 copies/ml were found in 73.6%. These HIV status variables did not differ based upon alcohol use. CONCLUSIONS: The NOAH Study facilitates bidirectional translational investigation of alcohol's impact on PLWH. Translation of preclinical findings to PLWH permits confirmation of basic biological mechanisms in humans and also allows incorporation of sociobehavioral factors that may affect biology but are challenging to replicate in preclinical models.

Incidental Renal Lesions on Lumbar Spine MRI: Who Needs Follow-Up?

OBJECTIVE: Incidentally discovered renal lesions on lumbar spine MRI are a common occurrence. Many follow-up recommendations are generated by radiologists encountering renal lesions to help characterize the finding as a benign cyst or a more complex, potentially malignant lesion. We hypothesized that analysis of T2-weighted imaging features of incidentally discovered renal lesions could reliably distinguish complex renal lesions from simple cysts. MATERIALS AND METHODS: Two independent readers retrospectively evaluated 149 renal lesions identified on lumbar spine MRI examinations. Presence or absence of a complex renal lesion was determined using T2-weighted imaging only. Using dedicated renal cross-sectional imaging examinations as the reference standard, statistical analysis was performed to determine the accuracy of lumbar spine MRI in predicting a complex and potentially neoplastic renal lesion. RESULTS: Of 149 renal lesions, 115 were simple cysts, and 34 were complex renal lesions (20 Bosniak II cysts, nine renal cell carcinomas, three Bosniak IIF cysts, and two angiomyolipomas). Lumbar spine MRI readers identified 72 lesions as simple cysts and 77 lesions as complex renal lesions. Reader sensitivity for detection of a complex renal lesion on lumbar spine MRI was 94% (95% CI, 80-99%); specificity, 63% (95% CI, 53-72%); positive predictive value, 43% (95% CI, 37-49%); and negative predictive value, 97% (95% CI, 90-99%). Readers correctly identified all neoplastic and potentially neoplastic lesions (≥ Bosniak IIF). Interreader agreement was excellent (κ = 0.84). CONCLUSION: Follow-up imaging may not be required in all cases of incidentally discovered renal lesions on lumbar spine MRI. Analysis of T2-weighted imaging alone appears to reliably rule out neoplastic and potentially neoplastic complex renal lesions.

Binge Drinking's Effects on the Body.

Studies have focused on the effects of chronic alcohol consumption and the mechanisms of tissue injury underlying alcoholic hepatitis and cirrhosis, with less focus on the pathophysiological consequences of binge alcohol consumption. Alcohol binge drinking prevalence continues to rise, particularly among individuals ages 18 to 24. However, it is also frequent in individuals ages 65 and older. High blood alcohol levels achieved with this pattern of alcohol consumption are of particular concern, as alcohol can permeate to virtually all tissues in the body, resulting in significant alterations in organ function, which leads to multisystemic pathophysiological consequences. In addition to the pattern, amount, and frequency of alcohol consumption, additional factors, including the type of alcoholic beverage, may contribute differentially to the risk for alcohol-induced tissue injury. Preclinical and translational research strategies are needed to enhance our understanding of the effects of binge alcohol drinking, particularly for individuals with a history of chronic alcohol consumption. Identification of underlying pathophysiological processes responsible for tissue and organ injury can lead to development of preventive or therapeutic interventions to reduce the health care burden associated with binge alcohol drinking.

Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis.

In the current study, we used a mouse model and human blood samples to determine the effects of chronic alcohol consumption on immune responses during Mycobacterium tuberculosis (Mtb) infection. Alcohol increased the mortality of young mice but not old mice with Mtb infection. CD11b+Ly6G+ cells are the major source of IFN-α in the lungs of Mtb-infected alcohol-fed young mice, and IFN-α enhances macrophage necroptosis in the lungs. Treatment with an anti-IFNAR-1 antibody enhanced the survival of Mtb-infected alcohol-fed young mice. In response to Mtb, peripheral blood mononuclear cells (PBMCs) from alcoholic young healthy individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α than those from non-alcoholic young healthy LTBI+ individuals and alcoholic and non-alcoholic old healthy LTBI+ individuals. Our study demonstrates that alcohol enhances IFN-α production by CD11b+Ly6G+ cells in the lungs of young Mtb-infected mice, which leads to macrophage necroptosis and increased mortality. Our findings also suggest that young alcoholic LTBI+ individuals have a higher risk of developing active TB infection.

Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques.

The incidence of alcohol use disorder (AUD) is higher among people living with HIV (PLWH). The advent and continued development of antiretroviral therapy (ART) has significantly reduced mortality, shifting the course of HIV infection to a chronic illness. However, this is associated with an increased incidence of comorbid conditions, including type 2 diabetes mellitus, insulin resistance, and cardiovascular complications. Using a nonhuman primate model of simian immunodeficiency virus (SIV) infection, previous studies have demonstrated that chronic binge alcohol (CBA) administration decreases whole body insulin responsiveness, irrespective of ART administration. The objective of the current study was to determine the effects of CBA and ART on insulin-sensitive peripheral tissues before the development of overt clinical symptoms of SIV disease. Our results show that CBA reduced omental adipocyte cell size, increased collagen expression, and decreased the in vitro differentiation potential of adipose-derived stem cells. In contrast, it did not alter skeletal muscle or omental or hepatic expression of insulin signaling proteins. However, ART significantly decreased skeletal muscle expression of phosphatase and tensin homolog, total mechanistic target of rapamycin, and ribosomal protein S6. In addition, ART increased hepatic phosphorylation of AMP-activated protein kinase α and increased gene expression of key enzymes required for gluconeogenesis and fatty acid synthesis. These findings suggest that CBA and ART differentially promote adverse metabolic effects in an organ-specific manner that may underlie insulin resistance associated with alcohol, SIV, and ART. Whether this is translated in PLWH with AUD remains to be determined.

Ekosonic Endovascular System (EKOS) in a trauma patient with intracranial bleed, recent major surgery, and massive pulmonary embolus: A case report.

Pulmonary embolism is a life-threatening condition treated with anticoagulation and systemic thrombolysis when appropriate. In patients with contraindications to thrombolysis, catheter-directed thrombolysis may be considered. Here, we present a patient with massive pulmonary embolus and 3 contraindications to systemic thrombolysis who was successfully treated with pharmacomechanical thrombolysis using the Ekosonic Endovascular System.

Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration.

Alcohol use disorder (AUD) is a frequent comorbidity among people living with HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence to antiretroviral therapy (ART), as well as worsening immunological and virological indicators among PLWHA. Clinical studies indicate that higher viral loads increase sensitivity to alcohol in PLWHA. The factors that influence alcohol kinetics after HIV infection and initiation of ART are not well understood, limiting the information upon which interventions can be designed to ameliorate the impact of alcohol misuse on this vulnerable patient population. To better understand the relationship between viral load and alcohol kinetics, we measured changes in doses of intragastric ethanol administration to achieve target blood ethanol concentration (BEC) in a rhesus macaque model of chronic binge alcohol (CBA) administration and acute changes following a single acute binge dose of alcohol (ABA) pre- and post-simian immunodeficiency virus (SIV) infection, and following ART initiation. Our results from CBA (14 months)-administered SIV-infected male macaques showed that, following ART initiation, macaques required higher doses of alcohol to achieve a target peak BEC compared with non-ART-treated SIV-infected macaques. In animals given ABA, we found prolonged duration of elevated BEC and decreased elimination rate of alcohol that was not corrected following 7 weeks of ART. These findings suggest that binge drinking associated with AUD could negatively interact with HIV infection and enhance disease progression. These findings further support the need for implementation of behavioral or therapeutic interventions to decrease alcohol consumption to improve the quality of life in PLWHA.