Human immunodeficiency virus-associated neurocognitive disorders persist in the combination antiretroviral therapy era. CD4 nadir is a well-established predictor of cognition cross-sectionally, but its impact on longitudinal neurocognitive (NC) trajectories is unclear. The few studies on this topic examined trajectories of global cognition, rather than specific NC domains. The current study examined CD4 nadir in relation to domain-specific NC decline. 132 HIV + adults from the Temple/Drexel Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core Cohort were administered comprehensive NC assessments longitudinally, with last visit occurring an average of 12 years after CD4 nadir. Linear mixed models were used to examine CD4 nadir in relation to longitudinal NC trajectories in three empirically identified NC domains: speed/executive function (S/EF), visuospatial memory (VM), and verbal fluency (VF). CD4 nadir was associated with change in VF (p = 0.020), but not with S/EF or VM. Specifically, those with CD4 nadir < 200 demonstrated increasing VF over time (p = .002), whereas those with CD4 nadir > 200 demonstrated stable VF (p = .568), though these differing trajectories may partly reflect regression to the mean or differential practice effect. CD4 dynamics over time were analyzed as potential mechanisms for the identified associations, with mixed findings. While low CD4 nadir has been associated with weaker neurocognition among people living with HIV, the results of this study suggest that low CD4 nadir is not associated with ongoing decline a decade later. Nadir-related deficits in VF may be stable or even improve over time, possibly reflecting the beneficial cognitive effects of long-term treatment and immune reconstitution.

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome.

To gauge the safety and utility of extended tecovirimat/cidofovir for severe mpox, here we report our experience caring for 4 patients with mpox and advanced human immunodeficiency virus (HIV) at the Hospitals of the University of Pennsylvania during the 2022 global outbreak. Three patients had recurrent courses complicated by superinfections, coinfections and insufficient nutrition/housing, requiring extended tecovirimat (5-16 weeks) and cidofovir (1-12 doses) with probenecid and fluids. At follow-up, patients had undetectable HIV RNA on antiretrovirals, improved ulcers and stable renal function on antivirals. Serology guided cessation for one 7-month cidofovir course. Overall findings support a comprehensive approach of prolonged tecovirimat/cidofovir with antiretrovirals for severe mpox, while addressing social factors.

Objective:Human immunodeficiency virus (HIV) type 1 (HIV-1), cardiovascular disease, and HIV-associated neurocognitive disorders (HAND) disproportionately affect Black/African American individuals compared to other racial and ethnic groups. Understanding the mechanisms of cognitive health disparities is essential for developing policy and health interventions to combat such disparities. Cardiovascular risk factors/diseases are common comorbidities that likely contribute to cognitive health disparities among Black/African American people living with HIV (PWH), but their impacts on cognition longitudinally in this population are unclear. The current study examines the relationship between cardiovascular risk and cognitive functioning over time in Black/African American adults living with HIV.Participants and Methods:A sample of 122 Black/African American adults with HIV (ages 25-68, M=51.8, SD=7.7; 98% on antiretroviral therapy; 91% with undetectable viral load) were selected from the Drexel/Temple Comprehensive NeuroHIV Center, Clinical and Translational Research Support Core (CTRSC; based at Drexel University College of Medicine) Cohort. They completed longitudinal visits (300 total visits, average follow-up time=4.9 years) that included clinical interviews, medical record review, biometric measurements, and comprehensive neuropsychological assessments. Cardiovascular risk factors of interest were body mass index (BMI), waist-to-height ratio (WHtR), and a total vascular risk burden score (VBS) representing five risk factors: obesity, central obesity, diabetes, hyperlipidemia, and hypertension. Based on a prior principal component analysis, three cognitive domains were examined: (1) verbal fluency, (2) visual memory/visuoconstruction, and (3) motor speed/executive functions. Mixed models were used to examine domain-specific cognitive trajectories in relation to baseline cardiovascular risk factors and changes in cardiovascular risk factors.Results:Overall, cognitive test performance improved over time (pConclusions:Higher total vascular risk burden was associated with less favorable verbal fluency trajectories, reflecting the negative cognitive consequences of disorders such as diabetes, hyperlipidemia, and hypertension. Unexpectedly, greater increases in BMI and WHtR were associated with more favorable trajectories in motor speed and executive functioning. In this population, weight gain may be a proxy for other positive health factors, such as immune reconstitution, which will be examined in future analyses. Taken together, cardiovascular risk factors have heterogeneous associations with cognitive trajectories, emphasizing the importance of examining the mechanisms of these varying relationships. Future research will examine how social determinants of health, such as racial/ethnic discrimination, contribute to disparities in cardiovascular risk factors and cognitive outcomes.

Verbal memory was related to better MMT-R performance, but neither cognition nor MMT-R were good predictors of detectable vs. undetectable viral load. However, among those with low-level viral replication, poorer visuospatial memory and difficulty with simple MMT-R items were preliminarily related to higher viral load. Given the small sample, results are limited by low statistical power. Future research will further explore relationships among cognition, MMT-R, RNA, and regimen complexity in larger samples to inform development of tools to monitor adherence difficulties.

Objective:Approximately half of people living with HIV (PWH) experience HIV-associated neurocognitive disorders (HAND), yet HAND often goes undiagnosed. There is an ongoing need to find efficient, cost-effective ways to screen for HAND and monitor its progression in order to intervene earlier in its course and more effectively treat it. Prior studies that analyzed brief HAND screening tools have demonstrated that certain cognitive test pairs are sensitive to HAND cross-sectionally and outperform other screening tools such as the HIV Dementia Scale (HDS). However, few studies have examined optimal tests for longitudinal screening. This study aims to identify the best cognitive test pairs for detecting cognitive decline longitudinally.Participants and Methods:Participants were HIV+ adults (N=132; ages 25-68; 59% men; 92% Black) from the Temple/Drexel Comprehensive NeuroHIV Center cohort. Participants were currently well treated (98% on cART, 92% with undetectable viral load, and mean current CD4 count=686). They completed comprehensive neurocognitive assessments longitudinally (328 total visits, average follow-up time=4.9 years). Eighteen participants (14% of the cohort) demonstrated significant cognitive decline, defined as a decline in global cognitive z-score of 0.5 (SD) or more. In receiver operating characteristic (ROC) analyses, tests with an area under the curve (AUC) of greater than .7 were included in subsequent test pair analyses. Further ROC analyses examined the sensitivity and specificity of each test pair in detecting significant cognitive decline. Results were compared with the predictive ability of the Modified HIV Dementia Scale (MHDS).Results:The following test pairs demonstrated the best balance between sensitivity and specificity in detecting global cognitive decline: Grooved Pegboard dominant hand (GPD) and category fluency (sensitivity=.89, specificity=.60, AUC=.75, pConclusions:Several cognitive test pairs, particularly those that include GPD, are sensitive to HIV-associated cognitive change, and far more sensitive and specific than the MHDS. Cognitive test pairs can serve as valid, rapid, cost-effective screening tools for detecting cognitive change in PWH, thereby better enabling early detection and intervention. Future research should validate the present findings in other cohorts and examine the implementation of test pair screenings in HIV care settings. Most of the optimal tests identified are consistent with the well-established impact of HAND on frontal-subcortical motor and executive networks. The utility of category fluency is somewhat unexpected as it places more demands on temporal semantic networks; future research should explore the factors driving this finding, such as the potential interaction of HIV with aging and neurodegenerative disease.

Significance Existing screening tools for HIV-associated neurocognitive disorders (HAND) are often clinically impractical for detecting milder forms of impairment. The formal diagnosis of HAND requires an assessment of both cognition and impairment in activities of daily living (ADL). To address the critical need for identifying patients who may have disability associated with HAND, we implemented a low-cost screening tool, the Virtual Driving Test (VDT) platform, in a vulnerable cohort of people with HIV (PWH). The VDT presents an opportunity to cost-effectively screen for milder forms of impairment while providing practical guidance for a cognitively demanding ADL. Objectives We aimed to: (1) evaluate whether VDT performance variables were associated with a HAND diagnosis and if so; (2) systematically identify a manageable subset of variables for use in a future screening model for HAND. As a secondary objective, we examined the relative associations of identified variables with impairment within the individual domains used to diagnose HAND. Methods In a cross-sectional design, 62 PWH were recruited from an established HIV cohort and completed a comprehensive neuropsychological assessment (CNPA), followed by a self-directed VDT. Dichotomized diagnoses of HAND-specific impairment and impairment within each of the seven CNPA domains were ascertained. A systematic variable selection process was used to reduce the large amount of VDT data generated, to a smaller subset of VDT variables, estimated to be associated with HAND. In addition, we examined associations between the identified variables and impairment within each of the CNPA domains. Results More than half of the participants (N = 35) had a confirmed presence of HAND. A subset of twenty VDT performance variables was isolated and then ranked by the strength of its estimated associations with HAND. In addition, several variables within the final subset had statistically significant associations with impairment in motor function, executive function, and attention and working memory, consistent with previous research. Conclusion We identified a subset of VDT performance variables that are associated with HAND and assess relevant functional abilities among individuals with HAND. Additional research is required to develop and validate a predictive HAND screening model incorporating this subset.

BACKGROUND:Interventions to promote medication adherence and viral suppression are needed among HIV-positive individuals. We aimed to determine the feasibility, acceptability, and preliminary impact of daily financial incentives linked to real-time adherence monitoring among treatment-experienced individuals.METHODS:At an HIV clinic in Philadelphia, we conducted a pilot randomized trial among treatment-experienced HIV-positive adults with unsuppressed viral loads (>400 copies/mL). Participants randomized to the intervention group were eligible for daily lottery-based financial rewards dependent on antiretroviral therapy (ART) adherence, measured by a wireless-enabled electronic pill bottle. Participants also received a financial incentive for achieving viral suppression at 3 months. The control group received the standard of care. We measured acceptance and feasibility through follow-up survey at 3 months, viral suppression at 3 months, and adherence.RESULTS:Among 29 participants, 28 (93%) completed 3-month follow-up, and 24 (83%) completed a 3-month laboratory visit. Electronic pill bottles were highly acceptable to participants, with most strongly agreeing that they worked well, were reliable, and easy to use. Among those who received the intervention, 77% were very satisfied with their experience. Among those who completed the 3-month laboratory visit, viral suppression was achieved by 40% in the intervention group and 29% in the control group. ART adherence ≥80% was achieved by 36% and 25% in the intervention and control groups, respectively.CONCLUSIONS:Daily financial incentives coupled with real-time adherence monitoring are a promising strategy to support ART adherence among HIV-positive individuals who are not virally suppressed. This novel approach warrants testing in a larger trial.

Abstract Background Pre-exposure prophylaxis (PrEP) is a highly effective daily oral antiretroviral medication that was approved by the FDA in 2012 and has been shown to reduce the risk of HIV by 95% in real-world studies. Despite this, many healthcare providers are not offering PrEP to their patients who are at risk for HIV. Methods We performed a cross-sectional study among Drexel Internal Medicine, Family Medicine, and Obstetrics and Gynecology residents. The survey included questions about experience, knowledge, attitudes toward and barriers to using PrEP. The survey was adapted from previous studies regarding medical providers’ attitudes and knowledge about PrEP (Petroll, 2016; Seifman, 2016; Blumenthal, 2105). A Likert 5-point scale was used for attitude and barriers questions. Results Among 143 participants, 80% specialized in Internal Medicine. 43% of participants were in their first year of training and the mean age (+ SD) was 28.8 + 2. 76% reported never initiating a conversation about PrEP with a patient and only 18% reported ever prescribing PrEP to their patients. 92% reported being very or extremely willing to prescribe PrEP to a male with a current male partner known to be HIV positive. Only 43% of residents reported being moderately likely to prescribe PrEP to a patient coming in for a STI exposure. 68% of residents reported their knowledge about PrEP was a major barrier to prescribing PrEP. Conclusion We found that most residents have minimal experience with prescribing PrEP, and knowledge was identified as the largest barrier. Additional education and a better understanding of PrEP indications is necessary to ensure eligible PrEP patients have access to this highly effective HIV prevention method. Disclosures All Authors: No reported disclosures

Abstract Background We performed a retrospective cohort study of treatment-naive patients with newly diagnosed HIV-infection enrolled at an urban university specialty clinic to identify whether INSTI-based ART regimens were associated with greater weight gain compared to NNRTI and PI based regimens in the first 12-18 months of treatment. The secondary aim of this study was to determine differences in weight gain between males and females within each of the three ART classes Methods Differences in weight change and BMI change were compared across ART class using nonparametric tests, specifically the Wilcoxon rank sum test. Nonparametric tests were also used to compare differences in weight change and BMI change between males and females within each ART class. Data were analyzed using R Core Team, 2020 Results Among the 348 individuals included in the study, 73% were African American and 79% were male and the median age was 32 years. There were 155 individuals initiating therapy on NNRTI based regimens (44%), 58 were on PI based regimens (17%) and 135 were on INSTI regimens (39%). The median weight at baseline was 170.5 lbs. and the median body mass index was 25.4 kg/m2. Median weight increased across all 3 ART regimens within the first 12-18 months of treatment. Median weight gain among the PI group was the greatest, at 6.8 lbs. (p= 0.04). Median weight gain among the NNRTI group was the lowest, .88 lbs (p=< .01). Median weight gain among those on INSTI based regimens was 4.8 lbs. (p= 0.11). Among those on INSTI-based regimens, women had a greater median increase in weight compared to men, 10.1 lbs. compared to 3.2 lbs., (p=0.046). Conclusion Overall, among individuals initiating HIV treatment those initiating PI based regimens experienced the most weight gain and individuals initiating INSTI based regimens did not experience a significant weight gain. Women on INSTI based regimens did experience a significant weight gain in comparison to men.. More research is needed to elucidate specific ART regimens’ causal role in weight gain and to identify risk factors for ART-associated weight gain. Disclosures All Authors: No reported disclosures

The CRISPR/Cas9 system has been proposed as a cure strategy for HIV. However, few published guide RNAs (gRNAs) are predicted to cleave the majority of HIV-1 viral quasispecies (vQS) observed within and among patients. We report the design of a novel pipeline to identify gRNAs that target HIV across a large number of infected individuals. Next generation sequencing (NGS) of LTRs from 269 HIV-1-infected samples in the Drexel CARES Cohort was used to select gRNAs with predicted broad-spectrum activity. In silico , D-LTR-P4-227913 (package of the top 4 gRNAs) accounted for all detectable genetic variation within the vQS of the 269 samples and the Los Alamos National Laboratory HIV database. In silico secondary structure analyses from NGS indicated extensive TAR stem-loop malformations predicted to inactivate proviral transcription, which was confirmed by reduced viral gene expression in TZM-bl or P4R5 cells. Similarly, a high sensitivity in vitro CRISPR/Cas9 cleavage assay showed that the top-ranked gRNA was the most effective at cleaving patient-derived HIV-1 LTRs from five patients. Furthermore, the D-LTR-P4-227913 was predicted to cleave a median of 96.1% of patient-derived sequences from other HIV subtypes. These results demonstrate that the gRNAs possess broad-spectrum cutting activity and could contribute to an HIV cure.

Among 146 urban heterosexuals screening negative for human immunodeficiency virus, one third anticipated increased sexual risk taking with human immunodeficiency virus preexposure prophylaxis. Men (vs. women) and black (vs. white) participants had increased odds for anticipating decreased condom use. Men and persons reporting transactional sex expected to increase sexual partnerships. Risk compensation could affect reproductive health and disease control.

ObjectiveAdoption of pre-exposure prophylaxis (PrEP) to prevent HIV infection has been slow. The purpose of this study was to evaluate knowledge, attitudes and referral practices for PrEP among non-prescribing providers, who may play key role.MethodsWe performed a cross-sectional survey on PrEP knowledge, attitudes, and referral practices among 66 non-prescribing HIV prevention providers (1st August to 31st December, 2016), in Philadelphia, followed by qualitative interviews with 12 of them (5th April to 10th May, 2017).ResultsParticipants had a mean age of 36 years, with 62% females. Majority were HIV case managers and rapid testers. For half of the respondents, PrEP eligibility screening was part of rapid HIV testing at their organization, 40% never had PrEP training and only 27% indicated personally screening clients for eligibility. Qualitative data revealed that participants held positive attitudes about PrEP and perceived organizational support, but had concerns about potential negative impacts and barriers to routine HIV screening.ConclusionResults highlight the importance of training non-prescribing HIV prevention providers about PrEP, addressing their concerns, and incorporating PrEP screening and referral into routine HIV testing.

Background Research surrounding attitudes and intentions concerning pre-exposure prophylaxis (PrEP) among at-risk heterosexuals, women and ethnic and racial minorities is needed to inform programs to scale this effective HIV prevention intervention among these populations.METHODS:The study sample includes 192 HIV-negative heterosexuals recruited from HIV testing sites operating in high HIV prevalence neighbourhoods in a mid-Atlantic city. Participants received brief educational sessions on PrEP and completed a self-administered survey assessing sociodemographic factors, HIV risk behaviours and theoretical determinants of PrEP uptake, based on the Theory of Planned Behaviour.RESULTS:Participants were majority persons of colour (86%), with a median age of 43 years. Compared with Whites, a higher percentage of Black and Brown persons had more than five sex partners (75.0%), used condoms inconsistently (85.6%) and engaged in transactional sex (84.4%). Most expressed positive PrEP attitudes and indicated intention to adopt PrEP, especially if recommended by their doctor. In a multivariable model, willingness to take PrEP if suggested by a healthcare provider (aOR: 4.17; 95% CI: 1.42-12.24) and willingness to take PrEP even if it caused side-effects (aOR: 1.98; 95% CI: 1.01-3.90) were both associated with greater PrEP adoption intentions.CONCLUSIONS:A diverse at-risk population was identified through community-based HIV testing. Low perceived HIV risk, as well as PrEP-related attitudes, subjective norms and perceived behavioural control were associated with PrEP use intentions. These factors are potential targets for interventions to increase PrEP adoption among diverse heterosexual samples.

Human immunodeficiency virus type 1 (HIV-1) encodes for Tat, a multi-functional regulatory protein involved in transcriptional enhancement and in causing neurotoxicity/central nervous system (CNS) dysfunction. This study examines Sanger sequencing of HIV-1 subtype B Tat from 2006 to 2014 within the Drexel University College of Medicine CNS AIDS Research and Eradication Study (CARES) Cohort to investigate Tat length in patients. The Los Alamos National Laboratory (LANL) database was used as a comparator. Miscoded stop codons were present in the CARES Cohort and LANL and protein variability was highly similar. Tat proteins in CARES and LANL were predominantly 101 residues. There was no observed correlation between Tat length and clinical parameters within the CARES Cohort. Unique Tat lengths found in the CARES Cohort and not in LANL were 31, 36, and 39 residues. When CARES patients were longitudinally examined, sequence lengths of 101 had a low probability of reducing to below 48, and sequences had a high probability of increasing to above 86 residues during their next visit, when below 48 residues in length. This suggests that Tat length is conserved to retain the majority of the proteins function highlighting its importance in viral replication.