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Opioid use has negative effects on immune responses and may impair immune reconstitution in persons living with HIV (PLWH) infection undergoing antiretroviral treatment (ART). The effects of treatment with μ opioid receptor (MOR) agonists (e.g., methadone, MET) and antagonists (e.g., naltrexone, NTX) on immune reconstitution and immune activation in ART-suppressed PLWH have not been assessed in-depth. We studied the effects of methadone or naltrexone on measures of immune reconstitution and immune activation in a cross-sectional community cohort of 30 HIV-infected individuals receiving suppressive ART and medications for opioid use disorder (MOUD) (12 MET, 8 NTX and 10 controls). Plasma markers of inflammation and immune activation were measured using ELISA, Luminex, or Simoa. Plasma IgG glycosylation was assessed using capillary electrophoresis. Cell subsets and activation were studied using whole blood flow cytometry. Individuals in the MET group, but no in the NTX group, had higher plasma levels of inflammation and immune activation markers than controls. These markers include soluble CD14 (an independent predictor of morbidity and mortality during HIV infection), proinflammatory cytokines, and proinflammatory IgG glycans. This effect was independent of time on treatment. Our results indicate that methadone-based MOUD regimens may sustain immune activation and inflammation in ART-treated HIV-infected individuals. Our pilot study provides the foundation and rationale for future longitudinal functional studies of the impact of MOUD regimens on immune reconstitution and residual activation after ART-mediated suppression.

Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

We aimed to discover barriers and facilitators of HIV pre-exposure prophylaxis (PrEP) adherence in young men and transgender women of color who have sex with men (YMSM/TW). Short-term and sustained adherence were measured by urine tenofovir concentration and pharmacy refills, respectively. Optimal adherence was defined as having both urine tenofovir concentration consistent with dose ingestion within 48 hours and pharmacy refills consistent with ≥4 doses per week use. Participants completed semi-structured interviews exploring adherence barriers and facilitators. Participants (n=31) were primarily African-American (68%), mean age 22 years (SD: 1.8), and 48% had optimal adherence. Adherence barriers included stigma, health systems inaccessibility, side effects, competing stressors, and low HIV risk perception. Facilitators included social support, health system accessibility, reminders/routines, high HIV risk perception, and personal agency. Our findings identify targets for intervention to improve PrEP adherence in these populations, including augmenting health activation and improving accuracy of HIV risk perception.

Maximizing the impact of HIV pre-exposure prophylaxis (PrEP) requires optimizing access and adherence for those at risk of contracting HIV. This study examined challenges to the processes of accessing and adhering to PrEP encountered by participants from a large, U.S. urban clinical center and assessed the utility of objectively monitoring PrEP adherence via urine. Most participants (65%) reported starting PrEP within 1-3 months of hearing about it, although 35% of participants encountered a provider unwilling to prescribe PrEP. Self-reported adherence was high among this population, with remembering to take the medication reported as the major barrier to adherence (44%) rather than cost or stigma. Urine tenofovir (TFV) monitoring was highly acceptable to this population, and participants indicated greater willingness to undergo urine monitoring every 3 months compared to finger prick (dried blood spot), phlebotomy, or hair follicle testing. These findings highlight the importance of focusing efforts toward reducing obstacles to PrEP use and support the use of urine TFV adherence monitoring as a marker of PrEP adherence.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine is 99% effective in preventing HIV when taken daily. Young men/transgender women of color who have sex with men are the most at risk to become infected with HIV, with the lowest PrEP adherence. We investigated the association of depression, anxiety, and history of childhood trauma with PrEP adherence. PrEP adherence was measured by urine TDF testing. Patients were evaluated for depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and history of childhood trauma (Adverse Childhood Experiences [ACEs]). Urine TDF levels were compared across scores on each screening tool using a Student’s t-test. A p-value of ≤ 0.05 was considered significant. Thirty-one subjects (mean age: 21.7 years, SD: 2.8) were enrolled between 3/2015 and 7/2016. Lower PrEP adherence was associated with a GAD-7 score diagnostic for generalized anxiety (80.7% versus 92.7%, p = 0.04) and a high ACE score (4+) (84.5% versus 95.7%, p = 0.05). A PHQ-9 score diagnostic for major depression was not associated with PrEP adherence. The presence of generalized anxiety and a history of childhood trauma, but not major depression, were associated with decreased PrEP adherence. The benefits of mental health interventions and trauma-informed care in PrEP programs should be considered in larger studies to potentially increase adherence.

Objectives Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre-exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real-time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. Methods We developed a urine assay using high-performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log10 categories between 0 and 10 000 ng/mL. We validated the assay in three cohorts: (1) HIV-positive subjects with undetectable viral loads on a TDF/FTC-based regimen, (2) healthy HIV-negative subjects who received a single dose of TDF/FTC, and (3) HIV-negative subjects receiving daily TDF/FTC as PrEP for 24 weeks. Results The urine assay detected TFV with greater sensitivity than plasma-based measures and with a window of measurements within 7 days of the last TDF/FTC dose. Based on the urine log-linear clearance after the last dose and its concordance with all detectable plasma levels, a urine TFV concentration > 1000 ng/mL was identified as highly predictive of the presence of TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low adherence patterns within the last 48 h (> 1000 ng/mL versus 10–1000 ng/mL), as well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to measurement. Conclusions We provide proof of concept that a semiquantitative urine assay measuring levels of TFV could be further developed into a point-of-care test and be a useful tool to monitor adherence to PrEP.

Background HIV pre-exposure prophylaxis (PrEP) is 99% effective at preventing new HIV infections if taken daily. To be successful, PrEP requires concurrent efforts to optimize uptake, persistence, and adherence. In 2018, cisgender (cis) women accounted for 19% of new HIV infections in the US but comprised only 7% of all PrEP users. Studies show poor PrEP adherence amongst cis women, but there is a paucity of real-world clinical data describing PrEP adherence among cis women and gender minority people. Methods An adherence test that measures the concentration of tenofovir in urine samples using a liquid chromatography mass spectrometry (LC-MS/MS) was used to assess recent PrEP adherence at 8 clinics. Urine samples were collected during routine visits and analyzed using the LC-MS/MS assay. Test results were retrospectively paired with gender data, when available, and sex assigned at birth (SAAB) data. Adherence data were aggregated and analyzed to assess non-adherence proportions by sub-population. Results Gender data were available from 1,461 patients at 5 clinics, 1,344 (92%) of whom were cis males (Figure 1). From the 5 clinics where gender and SAAB data were available, 3,835 tests were conducted and 517 (13.5%) indicated non-adherence (Figure 2). 3 additional clinics conduct routine adherence testing and collect SAAB data (gender data not available). At these 8 clinics, SAAB data were available for 2,773 PrEP patients, totaling 5,602 urine tests (Figure 3). Among these 5,602 adherence tests, 813 (14.5%) indicated non-adherence (Figure 4). SAAB females demonstrated significantly higher non-adherence than SAAB males (22% vs 14%, p< 0.001). Across clinics, 89%-98% of PrEP patients are SAAB male (Figure 5). Within these 8 clinics, SAAB female demonstrated consistently higher non-adherence (17%-44%, vs 12%-17% for SAAB males) (Figure 6). Figures 1 and 2 Figures 3 and 4 Figures 5 and 6 Conclusion Real-world data align with nationwide trends in PrEP utilization and show that the majority of PrEP patients are cis men. When initiated on PrEP, cis women exhibit higher rates of non-adherence than cis men. These data underscore the need to collect gender-identity data to monitor PrEP disparities and suggest that greater efforts are needed to target PrEP access, utilization, and accompanying support services to cis women and gender minority groups. Disclosures All Authors: No reported disclosures

PURPOSE: To characterize perceived social support for young men and transgender women who have sex with men (YM/TWSM) taking HIV pre-exposure prophylaxis (PrEP). METHODS: Mixed-methods study of HIV-negative YM/TWSM of color prescribed oral PrEP. Participants completed egocentric network inventories characterizing their social support networks and identifying PrEP adherence-support figures. A subset (n=31) completed semi-structured interviews exploring adherence support and qualities of PrEP support figures. We calculated proportions of role types (e.g. family), individuals disclosed to regarding PrEP use, and PrEP-supportive individuals within each participant network. Interviews were analyzed using an inductive approach. RESULTS: Participants (n=50) were predominately African-American men who have sex with men (MSM). Median age was 22 years (Interquartile range [IQR]: 20–23). Biologic family were the most common support figures, reported by 75% of participants (mean family proportion 0.37 [Standard deviation (SD): 0.31]), followed by 67% reporting friends (mean friend proportion 0.38 [SD: 0.36]). The majority of network members were aware (mean disclosed proportion 0.74 [SD: 0.31]), and supportive (mean supportive proportion 0.87 [SD: 0.28]) of the participants’ PrEP use. Nearly all (98%) participants identified ≥1 figure who provided adherence support; more often friends (48%) than family (36%). Participants characterized support as instrumental (e.g. transportation); emotional, (e.g. affection); and social interaction (e.g. taking medication together). Key characteristics of PrEP support figures included closeness, dependability, and homophily (alikeness) with respect to sexual orientation. CONCLUSIONS: While most YM/TWSM identified family in their support networks, friends were most often cited as PrEP adherence-support figures. Interventions to increase PrEP adherence should consider integrated social network and family-based approaches. IMPLICATIONS AND CONTRIBUTIONS: This mixed-methods study of young men and transgender women of color using PrEP identified diversity in support network composition, with family members occurring most commonly but friends most often providing adherence support. Clinicians and researchers should be cognizant of support structures in the design and delivery of PrEP adherence interventions.

Tenofovir Disoproxil Fumarate (TDF) and tenofovir Alafenamide (TAF) are prodrugs of tenofovir and have excellent long-term efficacy and tolerability for the treatment of HIV. An objective marker of adherence to tenofovir-based therapy could be clinically useful in supporting adherence to TDF-based HIV pre-Exposure Prophylaxis (PrEP) in populations in whom, self-report has been shown to be unreliable, and could play a role in resource-limited settings to support HIV and hepatitis B treatment adherence. A semi-quantitative high-performance liquid chromatographymass spectrometry method for tenofovir quantification of urine samples was developed. This assay detects tenofovir concentration in log10 levels between 1 and 10,000 ng/mL, and was shown to distinguish between recent adherence and low/non-adherence to both TDF and TAF, with a concentration of >1000 ng/mL, highly predictive of medication ingestion in the last 24-48 hours. This assay was validated relative to other markers of adherence including dried blood spot and selfreport in a highly adherent population of PrEP patients, and tenofovir was shown to be stable at room temperature in urine for at least 14 days. The assay was successfully used in a clinical setting to maintain high PrEP adherence and retention in care of 50 young men who have sex with men (MSM) over 48 weeks, to assess PrEP adherence in youth with mental health conditions, and to monitor drug levels relative to plasma levels in a case study of chewed TDF/FTC (tenofovir/emtricitabine) for PrEP. Further studies are underway to implement the tenofovir urine assay to monitor adherence and pre-exposure prophylaxis, nationally and internationally.

BACKGROUND Pre-exposure prophylaxis (PrEP) for HIV prevention with daily tenofovir and emtricitabine is effective when taken consistently. Currently, there is no objective way to monitor PrEP adherence. Urine has been shown to be highly correlated with plasma tenofovir levels, with urine tenofovir levels >1000 ng/mL demonstrating recent (1-2 days) adherence to PrEP. SETTING This study was conducted at an urban community health center in Philadelphia, Pennsylvania. METHODS PrEP was administered to 50 young men who have sex with men and transgender women of color using weekly, biweekly, and/or monthly dispensation schedules. Primary objectives were retention at 48 weeks (in care at week 48 and completing ≥50% of medication pickups) and adherence assessed by urine tenofovir levels. Risk behaviors and sexually transmitted infection diagnoses were also collected. RESULTS Seventy percent of participants were retained in care at 48 weeks. The proportion of subjects with urine tenofovir consistent with recent adherence was 80, 74.4, 82.4, 82.4, and 69.7% at weeks 4, 12, 24, 36, and 48, respectively. Sixty-one sexually transmitted infections were diagnosed over 231 screenings throughout 48 weeks, with no significant change between the first and second 24-week periods (P = 0.43; 0 seroconversions). At week 48, more than half of subjects reported an increase or no change in condom use, an increase in their ability to discuss HIV with partners, and no change in number of sexual partners from baseline. CONCLUSIONS These data demonstrate PrEP can be successfully delivered to a high-risk population with high program retention and medication adherence measured by urine tenofovir levels.

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada®) given as pre-exposure prophylaxis (PrEP) successfully blocks HIV when taken once daily prior to potential HIV exposure. A 22-year-old male reported difficulty swallowing FTC/TDF for PrEP and subsequently began chewing the FTC/TDF tablets. Monthly urine samples assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated tenofovir levels >1,000 ng/ml, indicative of protection from HIV acquisition, over a 48-week period. Data from observational studies of HIV-positive patients details the successful treatment of HIV using crushed FTC/TDF delivered via feeding and gastronomy tubes while small, randomized trials of healthy volunteers demonstrate bioequivalence between whole and crushed FTC/TDF.

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada

Objective Suicidal behavior (suicidal ideation, suicide attempts, and suicide completion) has been increasingly linked with difficulty initiating sleep, maintaining sleep, and early morning awakenings. However, the relationship between suicidal behavior and sleep duration abnormalities is unclear, especially at the population level. The present study used a nationally representative sample to examine the association of suicidal ideation with extreme sleep durations and insomnia symptoms. Method Cross-sectional data from adult respondents (≥ 18 years of age, N = 6,228) were extracted from the 2007-2008 wave of the National Health and Nutritional Examination Survey. Ordinal logistic regression analyses were used to evaluate the relationship of suicidal ideation with sleep duration, global insomnia, and individual insomnia symptoms in models adjusted for sociodemographic, socioeconomic, and health-related covariates. Results Suicidal ideation was associated with abnormalities of sleep duration. This relationship ceased to exist once the model was adjusted for depressive symptoms. As expected, an increased level of suicidal ideation was consistently associated with insomnia. Of the insomnia symptoms, difficulty maintaining sleep was found to be the most predictive of suicidal ideation, followed by difficulty initiating sleep (P Conclusions Abnormalities of sleep duration and continuity should prompt a clinical assessment for suicide risk.

Intimate partner violence (IPV) is a worldwide health concern and an important risk factor for poor mental/physical health in both women and men. Little is known about whether IPV leads to sleep disturbance. However, sleep problems may be common in the context of IPV and may mediate relationships with mental/physical health. Data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) were used ( N = 34,975). IPV was assessed in female and male participants for any history of being threatened by, physically hurt by, or forced to have sex with an intimate partner (THREAT, HURT, and SEX, respectively), and, further, as being forced to have sex with or physically injured by an intimate partner within the past year (SEXyr and HURTyr, respectively). These survey items were coded yes/no. Sleep disturbance was assessed as difficulty falling asleep, staying asleep, or sleeping too much at least 6 of the last 14 days. Logistic regression analyses, adjusted for age, sex, race, income, education, and physical/mental health, assessed whether IPV predicted sleep disturbance. Sobel–Goodman tests assessed whether relationships between IPV and physical/mental health were partially mediated by sleep disturbance. All IPV variables were associated with sleep disturbance, even after adjusting for the effects of age, sex, race/ethnicity, income, education, employment, marital status, physical health and mental health. THREAT was associated with sleep disturbance (odds ratio [OR] = 2.798, p < .0001), as was HURT (OR = 2.683, p < .0001), SEX (OR = 3.237, p < .0001), SEXyr (OR = 7.741, p < .0001), and HURTyr (OR = 7.497, p < .0001). In mediation analyses, all IPV variables were associated with mental health ( p < .0001), and all were associated with physical health ( p < .007) except SEXyr. Sleep disturbance partially mediated all relationships (Sobel p < .0005 for all tests). Mediation was around 30%, ranging from 18% (HURTyr and mental health) to 41% (HURT and physical health). IPV was strongly associated with current sleep disturbance above the effect of demographics and overall mental/physical health, even if the IPV happened in the past. Furthermore, sleep disturbance partially mediates the relationship between IPV and mental/physical health. Sleep interventions may potentially mitigate negative effects of IPV.