BACKGROUND: Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP. METHODS: Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence. RESULTS: Seventy-one participants were enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI .876, .923) per week, P < .001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P = .003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI .796 to .859) than among those with <80% (0.542, 95% CI95 .405 to .679) P < .001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (95% CI 1.033, 1.091) per year, P < .001; negative vs positive methamphetamine screen, OR 5.051 (95% CI 2.252, 11.494), P < .001. CONCLUSIONS: DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success.

Abstract: Background: HIV‐associated neurocognitive disorders (HAND) occur in ∼45% of people with HIV (PWH). Older PWH are at‐risk for both HAND and age‐associated disorders including Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Distinguishing aMCI from HAND among PWH is a diagnostic challenge given that both aMCI and HAND criteria include memory deficits. Differences between aMCI and HAND may include a more amnestic (recall and recognition deficits) and degenerative profile in aMCI versus milder (recall but not recognition deficits) and typically stable memory deficits in HAND. We exploited these differences to classify PWH based on aMCI+/‐ and HAND+/‐ status and compared trajectories of learning, recall and recognition performance among these classification groups. Method: Analyses included 685 PWH (ages 18‐79, 88% men) from the UCSD HIV Neurobehavioral Research Program. At baseline, aMCI status was determined based on a neuropsychological classification approach (Jak/Bondi) requiring impairment (<1.0 SD below normative mean) on two tests of recall and/or recognition (at‐least one recognition impairment required) from the Hopkins Verbal Learning Test‐Revised (HVLT‐R) and the Brief Visuospatial Memory Test‐R (BVMT‐R). HAND was diagnosed based on standard Frascati criteria. Using additive mixed model, trajectories of learning (averaged HVLT‐R and BVMT‐R learning scores), recall (averaged HVLT‐R and BVMT‐R recall scores) and HVLT‐R and BVMT‐R recognition z‐scores adjusted for age, sex, race and education were compared among classification groups. Result: Participants were classified into four groups: aMCI‐/HAND‐ (n=243), aMCI‐/HAND+ (n=199), aMCI+/HAND‐ (n=62) and aMCI+/HAND+ (n=181). There were significant diagnostic group X time interactions on learning and HVLT‐R and BVMT‐R recognition, but not recall (Figure 1). Learning showed significant change over time in the aMCI+/HAND+ and aMCI‐/HAND+ groups only. All groups showed significant, yet variable, patterns of change in HVLT‐R recognition. BVMT‐R recognition showed significant change over time in aMCI+/HAND‐ and aMCI+/HAND+ groups. Recall was poorest in the aMCI+/HAND+ versus other groups across time. Conclusion: Findings suggest that PWH with memory impairment combined with other cognitive deficits at baseline show the worst memory profiles over time. Research is needed into methods of differentiating other MCI subtypes from HAND and into potential compounding effects of AD‐ and HAND‐related pathologies.

Background

Heavy alcohol use negatively impacts neurocognition, but some studies report neurocognitive benefits associated with light drinking among HIV-seronegative (HIV-) older persons, suggesting a nonlinear or an inverted "J-shaped" association of alcohol consumption on neurocognition. Alcohol use is common among people with HIV (PWH); however, the association between recent "low-risk" alcohol consumption and neurocognition among PWH is poorly understood.

Methods

Participants included 310 PWH and 89 HIV- older (≥50 years) adults who reported alcohol abstinence or "low-risk" drinking, defined per the National Institute on Alcohol Abuse and Alcoholism criteria (i.e., ≥15 drinks/wk or ≥5 drinks/d for men; ≥8 drinks/wk or ≥4 drinks/d for women). Neurocognition was measured using global and domain-specific demographically corrected T-scores. Multiple linear regressions examined the interaction between total drinks in the last 30 days (linear and quadratic terms) and HIV serostatus on neurocognition, covarying for age, sex, lifetime major depressive disorder, lifetime nonalcohol substance use disorders, and lifetime alcohol use disorder.

Results

Total drinks consumed in the last 30 days did not differ by HIV serostatus (p = 0.202). Among HIV- older adults, quadratic effects of total drinks on neurocognition occurred such that optimal neurocognition (i.e., global function, executive function, learning, delayed recall, and motor skills) was detected at intermediate levels of "low-risk" drinking (~20 to 40 drinks), with poorer performance at the lower and higher ranges of "low-risk" consumption. In PWH, total drinks did not exhibit linear or quadratic associations with neurocognition.

Conclusions

In HIV- "low-risk" drinkers, intermediate levels of recent alcohol use were associated with better neurocognition, consistent with the inverted J-shaped association. The same nonlinear effect of recent alcohol consumption on neurocognition was absent in PWH, indicating there may be no beneficial or deleterious effects of low-risk alcohol consumption on neurocognition among PWH. Future research is warranted to examine associations between alcohol consumption and HIV-related biopsychosocial disadvantages that may supersede the neurocognitive benefits of alcohol.

Objective

Substance use disorders are highly comorbid with and contribute to the increased prevalence of neurocognitive dysfunction observed in HIV infection. Despite their adverse impact on everyday functioning, there are currently no compensatory-based neurorehabilitation interventions validated for use among HIV+ substance users (HIV/SUD). This study examined the effectiveness of goal management training (GMT) alone or GMT as part of a metacognitive training among HIV/SUD individuals with executive dysfunction.

Methods

Ninety HIV/SUD individuals were randomized to a single 15-min session: (1) GMT (n = 30); (2) GMT plus metacognitive training (neurocognitive awareness; GMT + Meta; n = 30); or (3) active control (n = 30). Following a brief neurocognitive battery and study condition, participants performed a complex laboratory-based function task, Everyday Multitasking Test (Everyday MT), during which metacognition (awareness) was evaluated.

Results

There was an increasing, but non-significant tendency for better Everyday MT performances across study conditions (Control ≤ GMT ≤ GMT + Meta; ps < .08). Post hoc analyses showed that GMT and GMT + Meta groups demonstrated small benefits (d = .20-.27) compared to the control arm but did not differ from one another (ds < .10). When GMT groups were combined, there were significant medium effect size benefits in Everyday MT performance and metacognitive task appraisals as compared to the control condition. Among participants who underwent GMT, benefits were most prominent in persons with poorer pre-training dual-tasking ability, depression, and methamphetamine use disorders (ds = .35-1.04).

Conclusions

A brief compensatory strategy has benefits for everyday multitasking and metacognition among HIV+ substance users with executive dysfunction. Future work exploring more intensive trainings, potentially complimentary to other restorative approaches and/or pharmacological treatments, is warranted.

Background

Initiation of antiretroviral therapy (ART) in early HIV infection demonstrates clinical benefits including enhanced CD4 T-lymphocyte recovery and minimization of the latent HIV reservoir. Whether ART intensification with CCR5 blockade provides additional benefits is unknown.

Trial design

This randomized controlled trial evaluated the impact of maraviroc (MVC) intensification in persons starting ART in acute and early HIV (AEH, within 3 months of estimated date of infection).

Methods

Twenty persons in AEH in San Diego underwent double-blind randomization to receive either standard of care (SOC) ART or SOC + MVC to evaluate the hypothesis that early CCR5 blockage with a CCR5-containing ART regimen may provide immunologic and clinical benefit. The primary outcome of this study was the difference from baseline to week 48 in the proportion of CCR5 CD4 memory T cells. Blood was drawn at baseline and weeks 12, 24, and 48 to evaluate CCR5 CD4 and CD8 T-cell dynamics using multicolor flow cytometry.

Results

MVC intensification (n = 10) did not significantly alter CCR5 T-cell dynamics at week 48 of study compared to SOC (n = 9) in this fully recruited study (mean 1.12 vs 0.63, t = 0.36, df = 16, P = 0.727). Exploratory analyses of additional T-cell subsets suggest that MVC intensification in AEH trended to early greater increases in naïve and activated and proliferating CD4 T cells (P = 0.11, 0.19), and greater decreases in senescent memory CD4 T cells (P = 0.06), but these differences did not remain by week 48. CD8 T-cell evaluations did demonstrate trends to differences at week 48 with slower increases in naïve cells and slower decreases in activated memory cells (P = 0.16, 0.09). There were no reported harms or significantly different adverse events.

Conclusions

We did observe a few trends, but did not find compelling evidence that MVC intensification during AEH significantly impacts CD4 and CD8 T-cell dynamics. Diagnosing and starting persons in AEH on ART may be of greater clinical importance than the regimen initiated.

The aim of the study was to evaluate the incidence of brain opportunistic pathologies and survival in patients living with HIV from a Romanian tertiary center. A 15-year prospective observational study of brain opportunistic infections diagnosed in HIV-infected patients was performed at Victor Babes Hospital, Bucharest, between January 2006 and December 2021. Characteristics and survival were compared related to modes of HIV acquisition and type of opportunistic infection. A total of 320 patients were diagnosed with 342 brain opportunistic infections (incidence 9.79 per 1000 person-years), 60.2% males with median age at diagnosis of 31 years (IQR 25, 40). Median CD4 cell count and VL were 36/μL (IQR 14, 96) and 5.1 log₁₀ copies/mL (IQR 4, 5.7) respectively. The routes of HIV acquisition were heterosexual (52.6%), parenteral route in early childhood (31.6%), injecting drug use (12.9%), men having sex with men (1.8%), and vertical (1.2%). The most common brain infections were progressive multifocal leukoencephalopathy (31.3%), cerebral toxoplasmosis (26.9%), tuberculous meningitis (19.3%), and cryptococcal meningitis (16.7%). Patients infected by parenteral mode in early childhood were younger at diagnosis of both opportunistic infection and HIV (p < 0.001 and p < 0.001, respectively), developed more frequently PML (p < 0.001), and had the lowest early (p = 0.002) and late (p = 0.019) mortality rates. Risk factors for shorter survival were age > 30 years (p = 0.001), injecting drug use (p = 0.003), CD4 +  < 100/μL (p = 0.007), and VL > 5 log₁₀ copies/mL at diagnosis (p < 0.001). The incidence and mortality rate of brain opportunistic infections were high and did not decrease significantly during the study period, due to late presentation or non-adherence to ART.

Deficits in social cognition are seen in both people living with HIV (PWH) and people with a history of methamphetamine (METH) dependence. Dually affected individuals may experience additive negative effects on social cognition due to these conditions. We evaluated social cognition in 4 diagnostic groups (HIV-/METH-, HIV-/METH+, HIV+/METH-, HIV+/METH+). First, we used traditional social-emotional functioning assessments, the Difficulties in Emotion Regulation Scale and the Faux Pas Task, to determine any significant effects of METH dependence and HIV on social cognition. Next, we quantified social cognition using the Human Behavioral Pattern Monitor by evaluating social behavior represented by interaction with novel objects. METH dependence significantly affected social-emotional functions and HIV significantly affected on object interactions, however no significant additive effects were observed using these methods. The nuanced relationship between HIV and METH dependence suggests that other factors (i.e., adaptive life skills) likely mediate social cognition-related behaviors.

Objective

The prevalence of older adults living with HIV is rising, as is their risk for everyday functioning problems associated with neurocognitive dysfunction. Multitasking, the ability to maintain and carry out subgoals in support of a larger goal, is a multidimensional skill ubiquitous during most real-life tasks and associated with prefrontal networks that are vulnerable in HIV. Understanding factors associated with multitasking will improve characterization of HIV-associated neurocognitive disorders. Metacognition is also associated with frontal systems, is impaired among individuals with HIV, and may contribute to multitasking.

Method

Ninety-nine older (≥50 years) adults with HIV completed: the Everyday Multitasking Test (MT), a performance-based measure during which participants concurrently attempt four everyday tasks (e.g., medication management) within a time limit; a comprehensive neuropsychological battery; measures of metacognition regarding their MT performance (e.g., metacognitive knowledge and online awareness).

Results

Better global neuropsychological performance (i.e., average T-score across all domains) was associated with better Everyday MT total scores (rho = 0.34; p < .001), as was global metacognition (rho = 0.37, p < .01). Bootstrapping mediation analysis revealed global metacognition was a significant partial mediator between neurocognition and Everyday MT (b = 0.09, 95% confidence interval [CI] = 0.01, 0.25). Specifically, metacognitive knowledge (but not online awareness) drove this mediation (b = 0.13, 95% CI = 0.03, 0.27).

Conclusions

Consistent with findings among younger persons with HIV, neuropsychological performance is strongly associated with a complex, laboratory-based test of everyday multitasking, and metacognition of task performance was a pathway through which successful multitasking occurred. Interventions aimed at modifying metacognition to improve daily functioning may be warranted among older adults with HIV.

Background

Alcohol use is a risk factor for nonadherence to antiretroviral therapy (ART) among people living with HIV/AIDS (PLWHA); however, differences in ART adherence across levels of alcohol use are unclear. This study examined whether "at-risk" alcohol use, defined by National Institute of Alcohol Abuse and Alcoholism guidelines, was associated with ART nonadherence among PLWHA.

Methods

Participants were 535 HIV-infected adults enrolled in studies at the HIV Neurobehavioral Research Program. ART nonadherence was identified by either self-reported missed dose or plasma viral load detectability (≥50 copies/ml). Potential covariates for multivariable logistic regression included demographics, depression, and substance use disorders.

Results

Using a stepwise model selection procedure, we found that at-risk alcohol use (OR = 0.64; p = 0.032) and low education (OR = 1.09 per 1 year increase in education; p = 0.009) significantly predict lower ART adherence.

Conclusions

A greater focus on the treatment of at-risk alcohol use may improve ART adherence among HIV-infected persons.

OBJECTIVES:Evidence of accelerated brain aging among HIV-infected adults argues for the increased risk of developing cerebral β-amyloid (Aβ) plaques. We compared the frequency of Aβ plaque-bearing cases in our HIV cohort with that in a general cohort reported by Braak et al. (2011). We explored post-translationally modified Aβ forms (N3pE, E22P, phospho-Ser8) in plaques and E22P-Aβ in the postmortem cerebrospinal fluid (CSF) in the HIV cohort. DESIGN:Clinicopathological study of HIV-infected adults. METHODS:To assess frontal Aβ plaque deposition, we conducted immunohistochemistry for generic Aβ (4G8) and three modified Aβ forms. We determined CSF E22P-Aβ levels by ELISA. RESULTS:We found 4G8-Aβ plaques in 29% of 279 HIV-infected cases. Within the age range of 31-70 years, the frequency of 4G8-Aβ plaque-bearing cases was higher in our HIV cohort (n = 273) compared with the general cohort (n = 1110) overall (29.3% vs. 25.8%) and across four age groups by decade (odds ratio 2.35, P < 0.0001). In HIV-infected cases with (n = 37) and without (n = 12) 4G8-Aβ plaques, modified Aβ forms occurred in order: N3pE, E22P, and phospho-Ser8. In CSF assays of HIV-infected cases with (n = 27; 17 focal, 10 widespread) and without (n = 11) 4G8-Aβ plaques, the median E22P-Aβ/Aβ40 ratio was higher among cases with widespread plaques than in cases with focal or absent plaques (P = 0.047). CONCLUSIONS:Our findings suggest HIV-infected adults are at increased risk of developing cerebral Aβ plaques. The occurrence of modified Aβ forms in order suggests the progression stages of Aβ plaque deposition. The potential for E22P-Aβ as a CSF biomarker of cerebral Aβ plaques should be investigated.