Search

People with HIV now have increased longevity; however, their health-related quality of life (HRQoL) still lags significantly compared to people without HIV. Perceived stress negatively impacts HRQoL, whereas psychosocial resources are linked to better HRQoL. This longitudinal analysis aims to explore the buffering role of psychosocial resources on the relationship between HRQoL and perceived stress. Participants (N = 240) included 142 persons with HIV (PwH) and 98 without HIV, M(SD) = 50.9(8.1) years. Multilevel models over four study years examined longitudinal relationships between HRQoL (outcome) and perceived stress (predictor) and potential moderation by psychosocial resources (personal mastery, social support, and resilience) by HIV serostatus. Among PwH only, personal mastery (p = 0.001), social support (p = 0.015), and resilience (p = 0.029) were associated with an attenuated effect of perceived stress (less negative slopes) for physical HRQoL over time. Bolstering personal mastery, social support, and resilience may have relevance for improving physical well-being among PwH.

Black and Latinx transgender women in the United States (U.S.) are at disproportionately high risk for HIV. Although HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection, uptake and persistence (i.e., ability to continue taking PrEP over time) can be a challenge for Black and Latinx transgender women due to myriad social and structural forces. In this qualitative study, we present unique data on the facilitators of PrEP persistence from Black and Latinx transgender women who initiated PrEP and exhibited varying levels of persistence during a demonstration project in Southern California. PrEP persistence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels on dried blood spot (DBS) samples collected at weeks 12 and 48. Informed by the socioecological framework, we conducted and analyzed interviews using qualitative content analysis to determine themes on the facilitators of PrEP persistence. Individual-level facilitators included the use of reminders, having high individual-level HIV risk perception, feeling empowered to take PrEP, and reporting having improved peace of mind and mental health because of taking PrEP. Interpersonal/Community-level facilitators included feeling motivation to prevent HIV in the community, motivation to prevent HIV in the context of sex work, and having high community-level risk perception. Structural-level facilitators included having positive experiences in affirming healthcare settings and having PrEP visits combined with other gender-related healthcare visits. Interventions aiming to increase PrEP uptake and persistence among Black and Latinx transgender women in the U.S. should harness the multiple levels of support exhibited by those who were able to start and persist on PrEP in the face of the myriad social and structural barriers.

BackgroundCisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence.MethodsAdherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations.ResultsPast-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable.ConclusionIPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence.Clinical trials registrationNCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aβ42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

The ability to maintain functional independence throughout the lifespan may be diminished among medically compromised and chronically stressed populations. People living with HIV are more likely to demonstrate functional impairment and report greater exposure to lifetime and chronic stressors than their seronegative counterparts. It is well-known that exposure to stressors and adversity is associated with functional impairment outcomes. However, to our knowledge, no studies have examined how protective factors such as psychological grit mitigate the negative effects of lifetime and chronic stressor exposure on functional impairment, and how this association differs by HIV-status. To address this issue, we studied associations between lifetime and chronic stressor exposure, grit, and functional impairment in 176 African American and non-Hispanic White HIV-seropositive (n = 100) and HIV-seronegative (n = 76) adults, aged 24-85 (M = 57.28, SD = 9.02). As hypothesised, HIV-seropositive status and lower grit, but not lifetime stressor exposure, were independently associated with more functional impairment. Moreover, there was a significant three-way interaction between HIV-status, grit, and lifetime stressor exposure, b = 0.07, p = 0.025, 95% CI [0.009, 0.135]. Specifically, lifetime stressor exposure was related to more functional impairment for HIV-seronegative-but not HIV-seropositive-adults who reported low levels of grit. These findings suggest that the protective effects of grit may differ across populations at risk for functional impairment.

BackgroundHIV-associated neurocognitive disorders (HANDs) remain prevalent despite antiretroviral therapy, particularly among older people with HIV (PWH). However, the diagnosis of HAND is labor intensive and requires expertise to administer neuropsychological tests. Our prior pilot work established the feasibility and accuracy of a computerized self-administered virtual reality program (DETECT; Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury) to measure cognition in younger PWH. The present study expands this to a larger sample of older PWH.MethodsWe enrolled PWH who were ≥60 years old, were undergoing antiretroviral therapy, had undetectable plasma viral loads, and were without significant neuropsychological confounds. HAND status was determined via Frascati criteria. Regression models that controlled for demographic differences (age, sex, education, race/ethnicity) examined the association between DETECT's cognition module and both HAND status and Global Deficit Score (GDS) derived via traditional neuropsychological tests.ResultsSeventy-nine PWH (mean age, 66 years; 28% women) completed a comprehensive neuropsychological battery and DETECT's cognition module. Twenty-five (32%) had HAND based on the comprehensive battery. A significant correlation was found between the DETECT cognition module and the neuropsychological battery (r = 0.45, P < .001). Furthermore, in two separate regression models, HAND status (b = -0.79, P < .001) and GDS impairment status (b = -0.83, P < .001) significantly predicted DETECT performance. Areas under the curve for DETECT were 0.78 for differentiating participants by HAND status (HAND vs no HAND) and 0.85 for detecting GDS impairment.ConclusionsThe DETECT cognition module provides a novel means to identify cognitive impairment in older PWH. As DETECT is fully immersive and self-administered, this virtual reality tool holds promise as a scalable cognitive screening battery.

ObjectiveLoneliness is prevalent in people with HIV (PWH) and associated with adverse health-related consequences, including depression. Chronic inflammation has been linked to depression in PWH, though its association with loneliness is less well established. Simultaneous examination of inflammation, loneliness and depression is needed to clarify these relationships. This study investigated the relationship between loneliness and inflammation, and the effects of loneliness and inflammation on depression in PWH.Methods82 PWH who were on suppressive ART (mean age [SD] = 53.2 [9.0]) completed the UCLA Loneliness Scale-Version 3 and the Center for Epidemiologic Studies Depression Scale as part of a comprehensive evaluation. Biomarkers of systemic inflammation (CRP, IL-6, CCL2/MCP-1, sCD14) and coagulation (D-dimer) were measured in blood using commercial immunoassays.ResultsMultivariable linear regression analyses revealed that higher D-dimer, CCL2/MCP-1, and sCD14 were significant predictors of loneliness (ps

During the COVID-19 pandemic, pre-exposure prophylaxis (PrEP) access and adherence decreased nationwide. This study examined pandemic-related disruptions to PrEP access and adherence among clients of a health center (Center) in Los Angeles, California. Clients (n = 25) and Center personnel (n = 11) completed qualitative interviews from March to July 2021. Although the Center provided options for remote PrEP care (i.e., telehealth, STI self-testing kits, and prescription delivery), clients experienced difficulty navigating services or lacked equipment for telehealth. More than half (n = 13) of clients discontinued PrEP during COVID-19 due to decreased sexual partners, relocation, or insurance status changes. Among those who continued PrEP, the majority reported no change in adherence, while a minority reported worsening adherence due to distractions/forgetting, prescription refill issues, lack of insurance coverage, and fear of completing in-person visits. Findings highlight the challenges of navigating PrEP services during COVID-19 and suggest PrEP services enhancement to adapt to crisis events.

BackgroundThe health status of people with HIV (PWH) influences their health-related quality of life (HRQOL). Modifiable lifestyle factors may improve HRQOL. This study (1) explores the association between modifiable lifestyle factors (physical activity and nutrition) and HRQOL and (2) examines if these lifestyle factors moderate the association health status and HRQOL.MethodsParticipants included 91 community dwelling PWH (age 36-65 years) from the university lab. Participants reported mental and physical HRQOL via the Medical Outcome Study 36-Item Short-Form (SF-36). Physical activity was examined via the International Physical Activity Questionnaire and nutrition (i.e., fruit and vegetable consumption) was assessed with the By-Meal Screener. Health status was ascertained via the Veterans Aging Cohort Study (VACS) Index.ResultsAim 1 analyses indicated that neither physical activity nor nutrition was related to mental HRQOL (p's > .05). However, greater physical activity (β = .33, p  .05).ConclusionPhysical HRQOL is related to self-reported physical activity and nutrition, with nutrition showing a moderating effect on the association between health status and physical HRQOL. Thus, future interventional studies designed to improve physical HRQOL should target both physical activity and nutrition.

ObjectiveTo determine whether a non‑platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma.MethodsGynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1-3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS.ResultsAt the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones.ConclusionsTopotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062.

Background: Men who have sex with men (MSM) who use stimulants are at increased risk for HIV infection. Adherence to pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection. We evaluated the efficacy of the individualized Texting for Adherence Building (iTAB) intervention for PrEP adherence compared to standard of care (SoC) among 119 MSM who use stimulants (cocaine, methamphetamine and/or other amphetamine) from the California Collaborative Treatment Group 595 randomized control trial.Method: Three ordered levels of PrEP adherence (non-adherence, adequate adherence, and near-perfect adherence) were compared between intervention arms across study visits (weeks 12 and 48) using ordinal logistic regressions.Results: The effect of intervention arm was not significant in the final model; however, there was a 38% decrease in odds (OR = 0.62, p=.023) of having near-perfect adherence (versus non-adherence or adequate adherence) at week 48 compared to week 12, indicating a significant effect of time. In a follow-up analysis examining week 48 only, logistic regression examining PrEP adherence showed that receiving iTAB (compared to SoC) trended toward higher odds of near-perfect adherence relative to adequate adherence (OR = 2.48, p=.061). Higher HIV knowledge resulted in higher odds (OR = 1.72, p=.020) of near-perfect adherence (versus non-adherence or adequate adherence).Conclusion: HIV knowledge may influence PrEP adherence, and most notably, the iTAB intervention may support near-perfect adherence relative to adequate adherence.

ObjectiveTo determine the reliability of teleneuropsychological (TNP) compared to in-person assessments (IPA) in people with HIV (PWH) and without HIV (HIV-).MethodsParticipants included 80 PWH (Mage = 58.7, SDage = 11.0) and 23 HIV- (Mage = 61.9, SDage = 16.7). Participants completed two comprehensive neuropsychological IPA before one TNP during the COVID-19 pandemic (March-December 2020). The neuropsychological tests included: Hopkins Verbal Learning Test-Revised (HVLT-R Total and Delayed Recall), Controlled Oral Word Association Test (COWAT; FAS-English or PMR-Spanish), Animal Fluency, Action (Verb) Fluency, Wechsler Adult Intelligence Scale 3rd Edition (WAIS-III) Symbol Search and Letter Number Sequencing, Stroop Color and Word Test, Paced Auditory Serial Addition Test (Channel 1), and Boston Naming Test. Total raw scores and sub-scores were used in analyses. In the total sample and by HIV status, test-retest reliability and performance-level differences were evaluated between the two consecutive IPA (i.e., IPA1 and IPA2), and mean in-person scores (IPA-M), and TNP.ResultsThere were statistically significant test-retest correlations between IPA1 and IPA2 (r or ρ = .603-.883, ps < .001), and between IPA-M and TNP (r or ρ = .622-.958, ps < .001). In the total sample, significantly lower test-retest scores were found between IPA-M and TNP on the COWAT (PMR), Stroop Color and Word Test, WAIS-III Letter Number Sequencing, and HVLT-R Total Recall (ps < .05). Results were similar in PWH only.ConclusionsThis study demonstrates reliability of TNP in PWH and HIV-. TNP assessments are a promising way to improve access to traditional neuropsychological services and maintain ongoing clinical research studies during the COVID-19 pandemic.

Positive psychological attributes are associated with better health outcomes, yet few studies have identified their underlying constructs and none have examined their temporal trajectories in clinical vs. non-clinical samples. From data collected over 4 years from people with HIV (PWH) and HIV-uninfected (HIV-) participants, we identified two latent factors (internal strengths; socioemotional support) based on responses to seven positive psychological attributes. Internal strengths increased over 4 years for PWH, but not for HIV- comparisons. Socioemotional support did not change significantly in either group. Lower internal strengths and worse socioemotional support were related to greater depressive symptoms. We speculate that improvement in internal strengths in PWH could reflect their being in care, but this requires further study to include PWH not in care. Given the apparent malleability of internal strengths and their association with improved health outcomes, these attributes can serve as promising intervention targets for PWH.

Gender-based violence (GBV) against transgender and nonbinary (TGNB) persons is a pervasive public health issue. GBV has been linked to mental health problems such as depression and posttraumatic stress disorder (PTSD), as well has risk for HIV seroconversion and HIV treatment nonadherence. However, the impact of GBV on HIV pre-exposure prophylaxis (PrEP) use among TGNB persons has yet to be investigated. In the current study we assessed longitudinal PrEP persistence data from dried blood spots (DBS) collected from 172 racially and ethnically diverse TGNB participants during a 48-week PrEP demonstration project in Southern California from June 2017 to September 2020. Participants were categorized into three levels of PrEP uptake and persistence based on their PrEP levels at the start and end of the study: low-low, high-low, and high-high. Individual-, social-, and structural-level variables were then entered into multinomial logistic regression models to predict levels of PrEP uptake and persistence based on hypotheses informed by syndemic and minority stress theories. The models demonstrated that experience of GBV predicted significantly lower odds of PrEP uptake and persistence and greater PTSD symptoms predicted significantly greater odds of early PrEP discontinuation. Higher levels of coping skills, already being on PrEP at baseline, and being in a steady relationship were associated with greater odds of PrEP uptake and persistence. Implications for future GBV research, advocacy, interventions, and much needed structural changes focused on improving the health and safety of TGNB individuals are discussed.

We determined the prevalence of Alzheimer's disease (AD) pathological hallmarks, amyloid-β and phosphorylated-Tau, in autopsied brains of 49 people with HIV (PWH) (ages: 50-68; mean age = 57.0) from the National NeuroAIDS Tissue Consortium and in a comparative cohort of 55 people without HIV (PWoH) from the UC San Diego Alzheimer's Disease Research Center (17 controls, 14 mild cognitive impairment, 24 AD; ages: 70-102, mean age = 88.7). We examined how AD pathology relates to domain-specific cognitive functions in PWH overall and in sex-stratified samples. Amyloid-β and phosphorylated-Tau positivity (presence of pathology of any type/density) was determined via immunohistochemistry in AD-sensitive brain regions. Among PWH, amyloid-β positivity ranged from 19% (hippocampus) to 41% (frontal neocortex), and phosphorylated-Tau positivity ranged from 47% (entorhinal cortex) to 73% (transentorhinal cortex). Generally, AD pathology was significantly less prevalent, and less severe when present, in PWH versus PWoH regardless of cognitive status. Among PWH, positivity for AD pathology related most consistently to memory-related domains. Positivity for p-Tau pathology related to memory-related domains in women with HIV only, although the sample size of women with HIV was small (n = 10). Results indicate that AD pathology is present in a sizable portion of middle aged and older PWH, although not to the extent in older PWoH. Studies with better age-matched PWoH are needed to examine the effect of HIV status on AD pathology.

BackgroundTransgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis.MethodsBetween June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages.ResultsAdherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone ( P < 0.001).ConclusionsIn addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.

BackgroundCardiovascular disease in individuals with mental health conditions such as bipolar disorder is highly prevalent and often poorly managed. Individuals with bipolar disorder face significant medication adherence barriers, especially when they are prescribed multiple medications for other health conditions including hypertension. Poor adherence puts them at a disproportionate risk for poor health outcomes. As such, there is a need for effective interventions to improve hypertension medication adherence, particularly in patients that struggle with adherence due to mental health comorbidity.MethodsThis 5-year project uses a 2-stage randomized controlled trial design to evaluate a brief, practical adherence intervention delivered via interactive text messaging (iTAB-CV) along with self-monitoring of medication taking, mood, and home blood pressure (N = 100) compared to self-monitoring alone (N = 100). Prior to randomization, all participants will view an educational video that emphasizes the importance of medication for the treatment of hypertension and bipolar disorder. Those randomized to the texting intervention will receive daily text messages with predetermined content to address 11 salient domains as well as targeted customized messages for 2 months. This group will then be re-randomized to receive either a high (gradual taper from daily to weekly texts) or low booster (weekly texts) phase for an additional 2 months. All participants will be monitored for 52 weeks. The primary outcomes are systolic blood pressure and adherence to antihypertensive medication as determined by a self-reported questionnaire and validated with an automated pill-monitoring device. Secondary outcomes include adherence to bipolar disorder medications, psychiatric symptoms, health status, self-efficacy for medication-taking behavior, illness beliefs, medication attitudes, and habit strength.DiscussionThis study specifically targets blood pressure and mental health symptom control in people with bipolar and includes implementation elements in the study design intended to inform future scale-up. Promising pilot data and a theoretical model, which views sustained medication-taking behavior in the context of habit formation, suggests that this remotely delivered intervention may help advance care for this high-risk population and is amenable to both scale up and easy adaptation for other groups with poor medication adherence.Trial registrationThe study was registered at ClinicalTrials.gov ( NCT04675593 ) on December 19, 2020.

Antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are key strategies in ending the HIV epidemic. However, poor adherence to daily ART and PrEP increases the risk of HIV transmission and acquisition. Long-acting ART and PrEP formulations attempt to improve adherence through providing long-lasting forms of the medication delivered through different routes of administration: oral (potentially monthly), injection (1-6 months), and subdermal implant (up to annually). This study explored patient and physician preferences for long-acting ART and PrEP as well as adherence support strategies. Adult patients (n = 42) with experience taking ART or PrEP participated in individual interviews or focus groups. Physicians (n = 13) currently prescribing ART and/or PrEP completed an online questionnaire. Rapid qualitative analysis systematically synthesized qualitative data, and descriptive statistics examined survey responses. Patients supported improved adherence as a top potential advantage of long-acting ART and PrEP, and reduced internal stigma as a strong benefit specific to long-acting ART. Annual coverage offered through subdermal implants had strong appeal; however, oral was the preferred modality for long-acting ART and PrEP. Patients preferred injectable ART and PrEP if concurrently receiving hormone therapy injections. Side effects, medication cost, and treatment accessibility were potential barriers. Patients preferred calendar tracking and text messages/phone reminders for adherence supports. Physicians reported that they would reduce clinic visits and HIV testing for all patients on long-acting PrEP, except men who have sex with men who would continue to complete HIV testing every 3 months. Physicians were mixed on whether they believed long-acting ART and PrEP would improve patient adherence. Overall, findings demonstrate the potential benefits of long-acting ART and PrEP, while highlighting the need to obtain additional information to address treatment concerns.

Background and objectivesTo determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with HIV (PWH).MethodsWe measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, and a neuropsychological test battery assessing 7 cognitive domains were administered to all participants at 2 study visits over an average of 6.5 months.ResultsPlasma eicosanoid concentrations were elevated in PWH (n = 95) compared with seronegative controls (n = 25) (100% prediction power at 5% false discovery rate [FDR], α = 0.0531) and were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated proinflammatory eicosanoids (24% prediction power at 5% FDR and 42.4% prediction power at 10% FDR, α = 0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not fully suppressed PWH.DiscussionThese data show that HIV infection is associated with a robust production of eicosanoids that are not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.

Objective: Poor sleep quality is related to worse neurocognition in older adults and in people with HIV (PWH); however, many previous studies have relied only on self-report sleep questionnaires, which are inconsistently correlated with objective sleep measures. We examined relationships between objective and subjective sleep quality and neurocognition in persons with and without HIV, aged 50 and older. Method: Eighty-five adults (PWH n = 52, HIV-negative n = 32) completed comprehensive neuropsychological testing to assess global and domain-specific neurocognition. Objective sleep quality was assessed with wrist actigraphy (total sleep time, efficiency, sleep fragmentation) for five to 14 nights. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. Results: Objective and subjective sleep measures were unrelated (p's > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%, p = 0.05) and were more likely to be using prescription and/or over the counter sleep medication (p = 0.04). In the whole sample, better sleep efficiency (p

BackgroundTo investigate joint contributions of cognitive and physiologic reserve to neurocognitive SuperAging in older persons with HIV (PWH).MethodsParticipants included 396 older PWH (age range: 50-69 years) who completed cross-sectional neuropsychological and neuromedical evaluations. Using published criteria, participants exhibiting global neurocognition within normative expectations of healthy 25-year-olds were classified as SuperAgers (SA; n = 57). Cognitively normal (CN; n = 172) and impaired (n = 167) participants were classified with chronological age-based norms. Cognitive reserve was operationalized with an estimate of premorbid verbal intelligence, and physiologic reserve was operationalized with a cumulative index of 39 general and HIV-specific health variables. Analysis of variance with confirmatory multinomial logistic regression examined linear and quadratic effects of cognitive and physiologic reserve on SA status, adjusting for chronological age, depression, and race/ethnicity.ResultsUnivariably, SA exhibited significantly higher cognitive and physiologic reserve compared with CN and cognitively impaired ( d s ≥ 0.38, p s < 0.05). Both reserve factors independently predicted SA status in multinomial logistic regression; higher physiologic reserve predicted linear increases in odds of SA, and higher cognitive reserve predicted a quadratic "J-shaped" change in odds of SA compared with CN (ie, odds of SA > CN only above 35th percentile of cognitive reserve).ConclusionsEach reserve factor uniquely related to SA status, which supports the construct validity of our SA criteria and suggests cognitive and physiologic reserve reflect nonoverlapping pathways of neuroprotection in HIV. Incorporation of proxy markers of reserve in clinical practice may improve characterization of age-related cognitive risk and resilience among older PWH, even among PWH without overt neurocognitive impairment.

ObjectiveGiven the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.MethodParticipants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.ResultsHIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).ConclusionsResults showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.

Despite the neurocognitive risks of aging with HIV, initial cross-sectional data suggest a subpopulation of older people with HIV (PWH) possess youthful neurocognition (NC) characteristic of SuperAgers (SA). Here we characterize longitudinal NC trajectories of older PWH and their convergent validity with baseline SA status, per established SuperAging criteria in PWH, and baseline biopsychosocial factors. Growth mixture modeling (GMM) identified longitudinal NC classes in 184 older (age ≥ 50-years) PWH with 1-5 years of follow-up. Classes were defined using 'peak-age' global T-scores, which compare performance to a normative sample of 25-year-olds. 3-classes were identified: Class 1Stable Elite (n = 31 [16.8%], high baseline peak-age T-scores with flat trajectory); Class 2Quadratic Average (n = 100 [54.3%], intermediate baseline peak-age T-scores with u-shaped trajectory); Class 3Quadratic Low (n = 53 [28.8%], low baseline peak-age T-scores with u-shaped trajectory). Baseline predictors of Class 1Stable Elite included SA status, younger age, higher cognitive and physiologic reserve, and fewer subjective cognitive difficulties. This GMM analysis supports the construct validity of SuperAging in older PWH through identification of a subgroup with longitudinally-stable, youthful neurocognition and robust biopsychosocial health.

ObjectiveThe aim of this study was to determine whether there are relationships between fatigue, cognition, and everyday functioning in older persons with and without HIV and to examine if associations remain after accounting for depression, anxiety, and sleep quality.MethodsSixty-nine persons with HIV (PWH) and 36 persons without HIV, aged 50-74 years, were recruited from ongoing studies at UC San Diego's HIV Neurobehavioral Research Program and from the community. Participants completed neuropsychological testing, a performance-based measure of everyday functioning, and self-report questionnaires of fatigue, depression, anxiety, sleep quality, and everyday functioning. Multivariable linear regressions and logistic regressions stratified by HIV serostatus were used to examine relationships between fatigue, cognition, and everyday functioning. Psychiatric symptoms and sleep quality were examined as covariates.ResultsIn this cross-sectional study, PWH had significantly greater fatigue than the HIV-negative group (g  = 0.83; P

BackgroundChronic inflammation contributes to the pathogenesis of depression in persons with HIV (PWH). Neopterin, a biomarker of HIV-related immune activation that partially normalizes with antiretroviral therapy (ART), correlates with major depressive disorder (MDD) and subclinical depressive symptoms in persons without HIV and acutely infected, young PWH. The sensitivity of neopterin, however, to both lifetime and current depression is poorly understood in older PWH on suppressive ART.MethodsParticipants were 70 PWH and 35 persons without HIV (HIV-) who were at least 50 years old and completed standardized neurobehavioral and neuromedical assessments. Depressive symptoms in the past 2 weeks, measured with the Beck Depression Inventory-II (BDI-II), and lifetime MDD diagnoses, defined as meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for a depressive episode at any point in one's lifetime, were separately modeled as a function of plasma neopterin levels in the full sample and by HIV serostatus.ResultsCompared with HIV- adults, PWH had higher neopterin levels (P < 0.001) and BDI-II scores (P < 0.01) and were more likely to have lifetime MDD (P < 0.01). Higher neopterin related to lifetime MDD, but only in PWH, even after controlling for clinically relevant comorbidities and treatment factors in logistic regression (odds ratio = 3.11, P = 0.002). Higher neopterin correlated with higher BDI-II scores in the full sample (rs = 0.25; P = 0.010), but not within either group (PWH: rs = 0.03, P = 0.819; HIV-: rs = 0.09, P = 0.588).ConclusionNeopterin was associated with lifetime MDD, but not current depressive symptoms in older PWH on suppressive ART. This may reflect a legacy of inflammation-related disruptions to amino acid metabolism and neurotransmitter synthesis, similar to prior observations. Identification of biopsychosocial and resilience factors underlying the null association between neopterin and current depression in older PWH is warranted.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in people with HIV (PWH). Studies suggested that certain sociodemographic factors are associated with the risk of HAND in PWH. Here we investigated the impact of HIV infection and demographics on functional brain networks. One run of 8.5 min resting state functional MRI (fMRI) data was collected from 101 PWH (41-70 years old) and 40 demographically comparable controls. Functional connectivity (FC) was calculated using average wavelet coherence. The impact of demographic factors on FCs was investigated using canonical correlation analysis (CCA). Wavelet coherence analysis revealed a reduced within-network connectivity in the dorsal somatomotor network (dSMN), along with a reduced between-network connectivity between dSMN and medial temporal lobe (MTL) in PWH (compared to controls). Across all participants, CCA revealed that older age and HIV infection had negative impacts on network connectivity measures (mainly reduced within- and between-network FCs), whereas education had an opposite effect. In addition, being female at birth or a member of a minority ethnic/racial group was also associated with network disruptions. Our data suggested that advanced age and HIV infection are risk factors for functional brain network disruptions, whereas higher educational attainment was linked to better preserved functional network connectivity.

HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV -) and lifetime MDD (MDD + /MDD -), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV - /MDD - , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD + . Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes.

BackgroundHIV PrEP effectiveness is highly dependent on adherence. High STI incidence has been reported among PrEP users. We assessed the relationship between STI incidence (CT, NG, and syphilis) and PrEP adherence.MethodsWe performed a subanalysis of a controlled, open-label, two-arm, randomized clinical demonstration project of a text-message based adherence intervention. Participants had 48 weeks of follow-up and had STI testing every 12 or 24 weeks. PrEP adherence was measured at week 48 using intracellular tenofovir-diphosphate drug concentrations. We calculated incidence rate ratios for STIs among those adherent as compared with those not adherent to PrEP.ResultsOf the 381 assessed for CT, NG and syphilis at one or more follow-up visits, there were 16 cases of syphilis or 5.0 per 100 person years (95% CI: 2.6, 7.5); 63 cases of NG or 26.3 per 100 person years (95% CI: 19.8, 32.8); and 81 cases of CT or 36.3 per 100 person years (95% CI: 28.4, 44.2). We found no association between adequate PrEP adherence and STI incidence (aIRR: 0.97 95% CI: 0.67, 1.40).ConclusionsWe found that the incidence of STIs was not significantly different between those adherent to PrEP and those non-adherent. Further research is needed to assess how PrEP use may impact STIs over time.

Given the co-occurrence of memory impairment in HIV-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment/Alzheimer's disease (aMCI/AD), biomarkers are needed that can disentangle these conditions among people with HIV (PWH). We assessed whether cerebrospinal fluid (CSF) markers of AD could help in this effort by determining their relationship to learning and memory deficits versus cognitive deficits more characteristic of HAND than aMCI/AD (processing speed and complex visual/motor coordination) among 31 older PWH. CSF amyloid-β42 phosphorylated-tau, amyloid-β40/amyloid-β42 and phosphorylated-tau/amyloid-β42 ratio related to learning/memory performance but not HAND-related deficits, suggesting that these biomarkers may have utility in disentangling aMCI/AD from HAND.

Older people with HIV (PWH) experience heightened risk for the acquisition of cumulative, multisystem decline, that is, frailty syndrome. Frailty relates to poorer sleep quality in the general older adult population; however, this association has yet to be explored among PWH. A cross-sectional analysis of 285 PWH ≥50 years of age (mean age 60.5 ± 7.0) examined the relationship between frailty (Fried frailty phenotype) and self-reported sleep quality [Pittsburgh Sleep Quality Index (PSQI)]. Three separate multivariable linear regression models examined global PSQI as a function of (1) frailty phenotype, (2) total number of frailty symptoms, or (3) specific individual frailty symptoms. Models covaried for demographic and biopsychosocial risk factors, including age, sex, race/ethnicity, education, premorbid verbal IQ estimate, current depressive symptoms, and diagnosis of a substance abuse disorder. Compared to nonfrail (B = 0.151; p = .021) and prefrail (B = 0.144; p = .021), frail phenotype was related to poorer sleep quality (increased global PSQI; F(5,278) = 11.34, p

BackgroundNeuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC).MethodsEleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1.ResultsCompared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS.ConclusionsCingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

BackgroundResearch suggests that physical activity (PA) has both acute and chronic beneficial effects on cognitive function in laboratory settings and under supervised conditions. Mobile health technologies make it possible to reliably measure PA and cognition in free-living environments, thus increasing generalizability and reach. Research is needed to determine whether the benefits of PA on cognitive function extend from the laboratory to real-world contexts.ObjectiveThis observational study aims to examine the association between daily fluctuations in PA and cognitive performance using mobile health technologies in free-living environments.MethodsA total of 90 adults (mean age 59, SD 6.3 years; 65/90, 72% men) with various comorbidities (eg, cardiovascular risk and HIV) and different levels of baseline cognition (ranging from cognitively normal to impaired) completed ecological momentary cognitive tests (EMCTs) on a smartphone twice daily while wearing an accelerometer to capture PA levels for 14 days. Linear mixed-effects models examined the daily associations of PA with executive function and verbal learning EMCTs. Moderation analyses investigated whether the relationship between daily PA and daily performance on EMCTs changed as a function of baseline cognition, cardiovascular risk, and functional status (independent vs dependent).ResultsDays with greater PA were associated with better (faster) performance on an executive function EMCT after covariate adjustment (estimate -0.013; β=-.16; P=.04). Moderation analyses (estimate 0.048; β=.58; P=.001) indicated that days with greater PA were associated with better (faster) executive function performance in individuals who were functionally dependent (effect size -0.53; P

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (

BackgroundEffective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease.MethodsWe conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions.ResultsA total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40).ConclusionsA multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis. (Funded by the National Heart, Lung, and Blood Institute; XPEL-TB ClinicalTrials.gov number, NCT03044158.).

Abstract The overall purpose of this qualitative study was to examine barriers and facilitators of successful aging among older men living with HIV (OMLH). Participants were recruited through HIV Neurobehavioral Research Program at the University of California, San Diego. Our sample included 14 OMLH: average age - 62 years old (range: 53 to 72), 79% white, 43% living alone, 79% men who have sex with men, 57% having college education or higher. Semi-structured interviews lasted from 43 to 114 minutes and were fully transcribed. Several themes emerged related to perceived barriers to successful aging stemming from social institutions: i.e., age discrimination and ageism, sexual and HIV-related stigma, social isolation, lack of resources, and food insecurity. Perceived institutional solutions promoting successful aging included mixed-age/inter-generational support groups, computer literacy training, health education, information and resources related to healthy lifestyle on a limited budget, and increased transparency of resources available to older adults.

Older people with HIV (PWH) experience increased risk of age-related neurodegenerative disorders and cognitive decline, such as amnestic mild cognitive impairment (aMCI). The objective of this study was to examine the relationship between aMCI and plasma VEGF biomarkers among older PWH. Data were collected at a university-based research center from 2011 to 2013. Participants were 67 antiretroviral therapy-treated, virally suppressed PWH. Participants completed comprehensive neurobehavioral and neuromedical evaluations. aMCI status was determined using adapted Jak/Bondi criteria, classifying participants as aMCI + if their performance was > 1 SD below the normative mean on at least two of four memory assessments. VEGF family plasma biomarkers (i.e., VEGF, VEGF-C, VEGF-D, and PIGF) were measured by immunoassay. Logistic regression models were conducted to determine whether VEGF biomarkers were associated with aMCI status. Participants were mostly non-Hispanic white (79%) men (85%) with a mean age of 57.7 years. Eighteen (26.9%) participants met criteria for aMCI. Among potential covariates, only antidepressant drug use differed by aMCI status, and was included as a covariate. VEGF-D was significantly lower in the aMCI + group compared to the aMCI - group. No other VEGF levels (VEGF, VEGF-C, PIGF) differed by aMCI classification (ps > .05). In a sample of antiretroviral therapy-treated, virally suppressed PWH, lower levels of VEGF-D were associated with aMCI status. Longitudinal analyses in a larger and more diverse sample are needed to support VEGF-D as a putative biological marker of aMCI in HIV.

ObjectivePeople with HIV (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared with the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH.DesignAnalysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort.MethodsFive hundred and twenty-four PWH over age 40 years were classified using Fried's Frailty criteria. Twelve comorbidities were documented from longitudinal data and associations between individual and co-occurring comorbidities with frailty were assessed using weighted network and logistic regression analyses.ResultsAt frailty assessment between 2015 and 2020, median age was 61 years, 76% were men, 94% were on antiretroviral therapy (ART), 73% had two or more comorbidities, 24% were frail, and 52% were prefrail. Among individual comorbidities, highest odds of frailty were in participants with depressive symptoms [adjusted odds ratio (aOR), 95% confidence interval (CI) 3.48 (2.22-5.46)], followed by bone disease and chronic obstructive pulmonary disease (COPD) [2.47 (1.28-4.72) and 2.13 (1.36-3.34), respectively]. Among co-occurring comorbidities, highest odds of frailty were in participants having depressive symptoms with diabetes, hypertension, or obesity [aORs (95% CIs) 5.29 (2.32-12.08), 5.21 (2.65-10.40), 4.85 (2.39-9.95), respectively], cognitive impairment with diabetes or renal disease [2.81 (1.38-5.68) and 2.53 (1.26-5.03), respectively], renal disease with cardiovascular disease [2.81 (1.32-6.01)], and diabetes with obesity [2.76 (1.39-5.45)].ConclusionCo-occurrence of depressive symptoms, cognitive impairment, diabetes, or renal disease with other medical conditions substantially increases odds of frailty in older PWH. Identifying and treating these comorbidities may help to reduce functional decline with aging in PWH.

The introduction of emtricitabine/tenofovir diphosphate (FTC/TDF) as pre-exposure prophylaxis (PrEP) for HIV prevention has raised questions regarding which clinicians will serve as prescribers and how providers will be educated about this HIV prevention strategy. We piloted an HIV Prevention Education Program called PrEP University (PrEP U) to address knowledge gaps in HIV prevention among medical trainees. We examined PrEP awareness and assessed learning as a result of the program, measuring knowledge before and after the lectures with an anonymous 5-question multiple choice test. A total of 198 learners participated in PrEP University, which included 127 first year medical students, and post-graduate trainees in internal medicine (n = 23), family medicine (n = 16), OBGYN (n = 13) and pharmacy (n = 19). Prior to PrEP U, 27% of all participants were not aware of PrEP and an additional 8% were unsure if they had heard of it. Knowledge increased significantly after the education program among trainees in OBGYN (2.3 vs 3.8, p

BackgroundPrior to implementing a pre-exposure prophylaxis (PrEP) demonstration study, we sought to explore cisgender women's experiences with HIV prevention, PrEP knowledge and attitudes, and anticipated barriers and facilitators for PrEP uptake and adherence in Southern California.MethodsThree focus groups were held with cisgender women of mixed HIV serostatus in San Diego and Los Angeles between November 2015 and January 2016. Women were recruited through local testing sites, community-based organizations, and social media. Focus groups were audio-recorded and transcripts were analyzed using thematic analysis.ResultsTwenty-two women participated in focus groups, with median age 44 (IQR 30-53) and 6 identifying as non-Hispanic Black, 7 non-Hispanic White, 8 Latina and 1 mixed race. Despite limited prior PrEP knowledge and no PrEP experience, participants expressed interest in taking PrEP. Anticipated benefits were freedom from worry about HIV and control over sexual health; however, these were tempered by concerns including the possibility of increased HIV risk behaviors and potential side effects. Cisgender women reported potential barriers to PrEP uptake and adherence barriers, like competing priorities and poor PrEP access. Conversely, PrEP facilitators included utilizing practical tools such as phone apps and pill boxes as well as receiving encouragement from loved ones and support from other cisgender women on PrEP, women living with HIV and their medical providers.ConclusionsAlthough PrEP awareness was low, participants recognized the importance of PrEP and ways to facilitate adherence. Exploring perspectives of cisgender women is integral to developing effective interventions to support PrEP uptake and adherence for women at elevated risk for HIV.

Little information is known about the cisgender women who seek and initiate pre-exposure prophylaxis (PrEP) for HIV prevention in the United States. Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week single-arm open-label demonstration study of daily oral tenofovir disoproxil fumaratel emtricitabine (TDF/FTC) in cisgender women ≥ 18 years old at risk for HIV. Participants were surveyed at screening and enrollment about sociodemographics, HIV risk perception and behaviors, and PrEP perspectives and aggregated into three risk groups according to HIV sexual risk behavior: being in a serodiscordant partnership (SD), engaging in sex work (SW), and having partners with unknown HIV status at risk for HIV (UP). One hundred sixty-seven women presented for screening with n = 31 screen failures. Of the 162 women completing enrollment, mean age was 40 (standard deviation 11), with 41% non-Hispanic Black, 22% non-Hispanic White, and 19% Latina. Compared with those who screened ineligible, enrolled participants were more likely to have heard of PrEP, had higher HIV risk perception, and reported higher perceived PrEP efficacy. Sixty-four women (47%) were categorized as SD, 21 (15%) as SW, and 51 (38%) as UP. The SW were more likely to report higher levels of drinking and drug use (p = 0.002) and history of intimate partner violence in the past year (p

BackgroundDaily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women.MethodsAdherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence.ResultsFrom June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections.ConclusionAdequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women.

BackgroundDaily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women.MethodsAdherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence.ResultsFrom June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections.ConclusionAdequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women.

ObjectivePeople with human immunodeficiency virus (HIV) (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared to the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH.DesignAnalysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort.Methods524 PWH over age 40 were classified using Fried's Frailty criteria. Twelve comorbidities were documented from longitudinal data and associations between individual and co-occurring comorbidities with frailty were assessed using weighted network and logistic regression analyses.ResultsAt frailty assessment between 2015-2020, median age was 61 years, 76% were male, 94% were on ART, 73% had two or more comorbidities, 24% were frail, and 52% were prefrail. Among individual comorbidities, highest odds of frailty were in participants with depressive symptoms (adjusted odds ratio [aOR], 95% confidence interval [CI] 3.48 [2.22-5.46]]), followed by bone disease and COPD (2.47 [1.28-4.72] and 2.13 [1.36-3.34], respectively). Among co-occurring comorbidities, highest odds of frailty were in participants having depressive symptoms with diabetes, hypertension, or obesity (aORs [95% CIs] 5.29 [2.32-12.08], 5.21 [2.65-10.40], 4.85 [2.39-9.95], respectively), cognitive impairment with diabetes or renal disease, (2.81 [1.38-5.68] and 2.53 [1.26-5.03], respectively), renal disease with cardiovascular disease (2.81 [1.32-6.01]), and diabetes with obesity (2.76 [1.39-5.45]).ConclusionsCo-occurrence of depressive symptoms, cognitive impairment, diabetes, or renal disease with other medical conditions substantially increases odds of frailty in older PWH. Identifying and treating these comorbidities may help to reduce functional decline with aging in PWH.

ObjectiveGiven the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.MethodParticipants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.ResultsHIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).ConclusionsResults showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (

Public randomization ceremonies have been proposed as a strategy to strengthen stakeholder engagement and address concerns and misconceptions associated with trial randomization. However, there are few published examples that describe how to conduct a public randomization ceremony with meaningful stakeholder engagement or how such ceremonies impact stakeholder perceptions about randomization and the randomization process. Cluster randomization for the GeneXpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial was conducted at a public randomization ceremony attended by 70 stakeholders in Kampala, Uganda. Presentations given by the Acting Assistant Commissioner from the Uganda National Tuberculosis and Leprosy Programme and trial investigators emphasized how the trial aimed to further national TB goals, as well as how stakeholders contributed to the intervention design. The purpose and process of randomization were described using simple text and visuals. Randomization was an interactive activity that required participation of stakeholders from each trial site. A survey administered to stakeholders at the end of the ceremony suggested high comprehension of randomization (98%), trust in the randomization process (96%), and satisfaction with randomization outcomes (96%). Public randomization ceremonies should be considered more routinely to engage stakeholders in and address potential concerns about the fairness and impartiality of the randomization process for community-based trials.

BackgroundPrior to implementing a pre-exposure prophylaxis (PrEP) demonstration study, we sought to explore cisgender women's experiences with HIV prevention, PrEP knowledge and attitudes, and anticipated barriers and facilitators for PrEP uptake and adherence in Southern California.MethodsThree focus groups were held with cisgender women of mixed HIV serostatus in San Diego and Los Angeles between November 2015 and January 2016. Women were recruited through local testing sites, community-based organizations, and social media. Focus groups were audio-recorded and transcripts were analyzed using thematic analysis.ResultsTwenty-two women participated in focus groups, with median age 44 (IQR 30-53) and 6 identifying as non-Hispanic Black, 7 non-Hispanic White, 8 Latina and 1 mixed race. Despite limited prior PrEP knowledge and no PrEP experience, participants expressed interest in taking PrEP. Anticipated benefits were freedom from worry about HIV and control over sexual health; however, these were tempered by concerns including the possibility of increased HIV risk behaviors and potential side effects. Cisgender women reported potential barriers to PrEP uptake and adherence barriers, like competing priorities and poor PrEP access. Conversely, PrEP facilitators included utilizing practical tools such as phone apps and pill boxes as well as receiving encouragement from loved ones and support from other cisgender women on PrEP, women living with HIV and their medical providers.ConclusionsAlthough PrEP awareness was low, participants recognized the importance of PrEP and ways to facilitate adherence. Exploring perspectives of cisgender women is integral to developing effective interventions to support PrEP uptake and adherence for women at elevated risk for HIV.