Objective:To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical parameters that correlate with these abnormalities.Methods:Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy for at least one year and plasma viral-load < 200 copies/ml) and in socio-demographically-matched controls without HIV (CWOH). The primary outcome measure of this cross-sectional analysis was increased WMH load, determined by total Fazekas score ≥ 2. Multiple logistic regression analysis was performed to evaluate the effect of HIV serostatus on WMH load, and to identify MRI, CSF and clinical variables that associate with WMH in PLWH group.Results:The study included 203 PLWH and 58 CWOH who completed a brain MRI scan between April 2014 and March 2019. The multiple logistic regression analysis, with age and history of tobacco use as covariates, showed that the adjusted odds ratio of the PLWH group for increased WMH load is 3.7 (95% confidence interval 1.8–7.5, p=0.0004). For the PLWH group, increased WMH load was associated with older age, male sex, tobacco use, hypertension, and hepatitis C virus co-infection, and also with the presence of measurable tumor necrosis factor-alpha in CSF.Conclusions:Our results suggest that HIV serostatus affects the extent of brain WMH. This effect is mainly associated with aging and modifiable co-morbidities.

Background As morbidity due to viral co-infections declines among HIV-infected persons, changes in liver related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV mono-infected patients in the combination antiretroviral therapy (cART) era. Methods Participants who were HBV and HCV seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase (ALT) elevations ≥ 1.25 times the upper limit of normal on at least two visits, for a duration of six months or more within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. Results Of 2,779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28 – 1.29). In an adjusted model, cLEE was associated with Hispanic/other ethnicity [Reference Caucasian: HR 1.744 (1.270 – 2.395)], non–nucleoside reverse transcriptase (NNRTI) based cART [Reference boosted protease inhibitors: HR 2.232 (1.378 – 3.616)], being cART naïve [HR 6.046 (3.686 – 9.915)] or having cART interruptions [HR 8.671 (4.651 – 16.164)]. African American race [HR 0.669 (0.510 – 0.877)] and integrase strand transfer inhibitor (INSTI) based cART [HR 0.222 (0.104 – 0.474)] were protective. Conclusions Our findings demonstrate initiation and continued use of cART is protective against cLEE and supports the hypothesis HIV infection directly impacts the liver. INSTI based regimens were protective and could be considered in persons with cLEE.

BackgroundNeurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them to HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and cerebrospinal fluid (CSF) analyses.MethodsParticipants underwent comprehensive neuropsychological (NP) testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching (CEM) was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes.ResultsData were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared to controls, PWH scored lower in the domains of attention/working memory (PWH Least Square Mean [LSM]=50.4 vs. controls LSM=53.1, p=0.008) and motor function (44.6 vs. 47.7, p=0.009), and a test of information processing speed (symbol search 30.3 vs. 32.2, p=0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p=0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p<0.05). PWH had reduced proportions of subcortical gray matter on MRI (β=-0.001, p<0.001) and CSF showed elevated levels of neurofilament-light chain (664 vs. 529 pg/mL, p=0.01) and TNF-α (0.229 vs. 0.156 ng/mL, p=0.0008).ConclusionsPWH, despite effective ART for over a decade, displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses revealed reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the already large proportion of virologically controlled PWH continues to grow, longitudinal studies should be conducted to elucidate the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.

The multiple regression model is very popular among researchers in both field of social and science because it is easy to interpret and have a well-established theoretical framework. However, the multioutput multiple regression model is actually widely applied in the engineering field because in the industrial world there are many systems with multiple outputs. The ridge regression model and the Multi-Layer Perceptron (MLP) neural network model are representations of the predictive linear regression model and predictive non-linear regression model that are widely applied in the world of practice. This study aims to build multi-output models of a ridge regression model and an MLP neural network whose hyperparameters are determined by a grid search algorithm through the cross-validation method. The hyperparameter that produces the smallest RMSE value in the validation data is chosen as the hyperparameter to train both models on the training data. The hyperparameter in question is a combination of learning algorithms and alpha values (ridge regression), a combination of the number of hidden nodes and gamma values (MLP neural network). In the ridge regression model for alpha in the range between 0.1 and 0.7, the smallest RMSE is obtained for all learning algorithms used. While the MLP neural network model specifically obtained a combination of the number of nodes = 18 and gamma = 0.1 which produces the smallest RMSE. The ridge regression model with selected hyperparameters has better performance (in the RMSE and R2 value) than the MLP neural network model with selected hyperparameters, both on training and testing data.

Background In the U.S., military members experience a higher incidence of sexually transmitted infections (STIs) than the age and gender-adjusted general population, placing a costly and preventable burden on the military health system (MHS). These increased rates are likely due to differences in both individual and network level risk factors. To assess the feasibility of a survey examining the impact of sexual network risk factors on risk, a survey assessing STI individual and network level risk factors to include a 90-day sexual partnership inventory was piloted at a single military medical center. Methods A sample of 50 military beneficiaries completed a computer-assisted self-interview (CASI) cross-sectional egocentric survey administered on a tablet. Demographical and clinical data were captured from the electronic medical record. Non-parametric statistics were used to analyze the data. Results 45 of 50 subjects (90%) completed the survey. 40 (88%) subjects completed at least one partnership survey and reported 1 to 20 partners per subject. Respondents were mostly active duty (91.8%) and had been active duty for less than five years (68.2%). Common risk behaviors were explored and included meeting partners online (68.75%) and having partners who use drugs (48.94%) or are heavy drinkers (44.68%). Partnership inventories suggest sexual concurrency and disassortative mixing on age, racial and ethnic groups, and military service. Conclusion While previous studies demonstrate that service members will complete sexual risk behavior surveys, this pilot egocentric partnership study demonstrates their willingness to provide detailed information on risk behaviors as well as detailed information on sexual partnerships. While we report on statistically significant associations, these may be subject to bias due to the underlying characteristics of the source population. As a result, these data will not likely be reflected in the full study population. 80% of pilot subjects completed the questionnaire and submitted at least one partnership survey, indicating the possibility of gathering more diverse individual sexual risk questionnaires from active duty service members. Based on these data, a multisite study of sexual networks was implemented in the MHS and is currently under analysis. Disclosures All Authors: No reported disclosures

Background Despite increasing attention to HIV-related stigma within the DoD, to date, the majority of research has focused on civilians, up to half of whom report perceived or experienced stigma. However, military service members and retirees with HIV may be particularly vulnerable to stigma and its adverse correlates. Methods The current study utilized cross-sectional data collected within the U.S. Military HIV Natural History Study. Participants completed questionnaires, including the Center for Epidemiologic Studies Depression scale, the Short Form Health Survey, the Internalization Subscale of the HIV Stigma Scale, and a measure of stigma experienced in the past year. Experiences of stigma were dichotomized to indicate presence or absence. Linear and logistic regressions were used to examine associations between internalized stigma and psychosocial functioning. All analyses were adjusted for age, race, sex, marital status, military rank, and duty status (i.e., active duty or retired). Results The sample comprised 399 participants (93.5% male; 46.0% Black/African American; Mage: 50.8 ± 13.2 years; Mage at HIV diagnosis: 31.9 ± 8.2 years; 32.4% on active duty). The majority (94.4%) had an undetectable viral load at the time of the visit. Fourteen percent reported being teased, treated unfairly, or discriminated against in the past year due to their HIV status, and 8% reported discrimination specifically within healthcare. Adjusting for covariates, internalized stigma was associated with poor physical (p &lt; .001) and overall mental (p &lt; .001) health. Internalized stigma was also associated with greater odds of reporting elevated depression (p &lt; .001). Conclusion In this sample of service members and retirees with HIV, a small but significant minority of participants reported experiencing stigma. Rates of stigma were lower than those observed in some civilian samples, though heterogeneity in sampling and methodology preclude direct comparisons. Internalized stigma was associated with poor physical and mental health, signaling a need for continued efforts to assess both experienced and internalized stigma. Future research should explore associations between stigma, ART adherence, and other metrics of health, such as CD4 count, substance use, and cardiometabolic risk. Disclosures All Authors: No reported disclosures.

Background Coccidioidomycosis ranges clinically from a self-limited respiratory illness to multi-organ dissemination. Based largely on skin testing from the 1940s, 60% of infections are thought to be asymptomatic. Limited Coccidioides seroincidence data support our understanding of the epidemiology and pathogenicity of this disease. Methods This retrospective cohort study tested 2000 U.S. military personnel for Coccidioides exposure after transfer to an endemic region of California between 2011 and 2017. The presence of IgG and IgM anti-Coccidioides antibodies were tested on pre- and post-transfer serum samples from the DoD Serum Repository to establish rates of seroconversion. Medical histories and participant demographics including race/ethnicity and military occupational specialty codes were collected from the electronic medical record and participants were stratified by a history of Coccidioides-specific or general respiratory illness based on ICD9/ICD10 coding. Results Thirty of 2000 participants tested newly positive for anti-Coccidioides antibodies after 12 months on station. Seroconversion incidence varied from 0.0-1.32 annually and overall 0.5 per 100 person years. Seroconverters were more frequently diagnosed with coccidioidomycosis or pneumonia than non-converters (p=0.027). No statistically significant association between demographic characteristics and seroconversion or disease was observed. Clinical disease was detected in only three seroconverters (10%). Incidence Rate of Coccidioidomycosis Infection among Active Duty Stationed at NAS Lemoore, 2011-2017 Seroconversion Status by Cocci/Pneumonia Diagnosis Status Conclusion In this study Coccidioides seroincidence was similar to that observed by others, adding longitudinal evidence to epidemiologic assumptions about coccidioidomycosis. A trend toward increasing incidence over the course of the study is consistent with the classification of coccidioidomycosis as an emerging infectious disease. While transmission is typically related to exposure, we did not detect a difference based on military occupational specialty codes. Overall, rates of diagnosed disease in our cohort were lower than the historically-assumed 40% symptomatic rate, although this conclusion is limited by the retrospective nature of the study. Further clinical and epidemiologic coccidioidomycosis research, particularly in broader endemic regions, is warranted. Disclosures All Authors: No reported disclosures

No abstract