Immune activation is associated with neurocognitive performance in Ugandan Adolescents living with HIV.

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 socio-demographically matched HIV- controls) completed a tablet-based neurocognitive test battery. Control derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T cell (expression of CD38 and HLA-DR on CD4+ and CD8+) activation and gut markers. Spearman's rank correlations and median regressions examined associations between test performance and immune activation. Median [IQR] age was 15[13-16] years, 40% were females. Median time on ART was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared to controls, global z-scores were lower among PHIV (p=0.05), and significantly worse on tests of executive functioning and delayed recall (p's≤0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r=0.21, p=0.04), attention, processing speed, and motor speed (r=0.2-0.3, p≤0.01). T cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r=0.2-0.4, p≤0.04). In PHIV, after adjusting for age, sex, and ART duration, activated CD4 T cells remained associated with worse memory (ß-0.3, 95% CI, -0.55, -.07, p=0.01). PHIV with virologic suppression on ART show evidence of worse neurocognitive test performance compared to controls. Monocyte and T cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV which has not been previously investigated in this setting.

"We did more than survive": lessons learned from studies of risk and resilience of young people growing up with HIV and mental health needs.

Despite advances in HIV-treatment, adolescents and young adults (AYA) with HIV (AYAHIV) face myriad challenges. They are less likely than children and older adults to be virally suppressed and are at higher risk for mental health conditions compared to their peers who do not have HIV. AYA are also developing in the context of numerous biomedical, neurocognitive, and psychosocial developmental changes. Normative challenges during this time can be exacerbated by HIV and can result in significant physical and mental health problems. Yet, many AYAHIV have shown resilience with positive assets and resources and few health or mental health problems. Historically research has had a risk-focused approach to understanding AYAHIV needs. This paper discusses the rationale for a shift from a risk-focused only approach to one that examines AYAHIV needs from both a risk and resilience perspective. This paper presents: (1) epidemiological data on AYAHIV; (2) conceptual models for understanding both risk (e.g., poverty, stress, trauma, limited resources) and resilience/protective factors (e.g., family and peer support, future orientation, problem-solving skills); (3) global data examining risk and protective factors for physical and mental health challenges; and (4) promising interventions that incorporate elements of resilience to improve overall outcomes among AYAHIV.

Comparative kinetics of humans and non-human primates during vertical climbing.

Climbing represents a critical behavior in the context of primate evolution. However, anatomically modern human populations are considered ill-suited for climbing. This adaptation can be attributed to the evolution of striding bipedalism, redirecting anatomical traits away from efficient climbing. Although prior studies have speculated on the kinetic consequences of this anatomical reorganization, there is a lack of data on the force profiles of human climbers. This study utilized high-speed videography and force plate analysis to assess single limb forces during climbing from 44 human participants of varying climbing experience and compared these data with climbing data from eight species of non-human primates (anthropoids and strepsirrhines). Contrary to expectations, experience level had no significant effect on the magnitude of single limb forces in humans. Experienced climbers did, however, demonstrate a predictable relationship between center of mass position and peak normal forces, suggesting a better ability to modulate forces during climbing. Humans exhibited significantly higher peak propulsive forces in the hindlimb compared with the forelimb and greater hindlimb dominance overall compared with non-human primates. All species sampled demonstrated exclusively tensile forelimbs and predominantly compressive hindlimbs. Strepsirrhines exhibited a pull-push transition in normal forces, while anthropoid primates, including humans, did not. Climbing force profiles are remarkably stereotyped across humans, reflecting the universal mechanical demands of this form of locomotion. Extreme functional differentiation between forelimbs and hindlimbs in humans may help to explain the evolution of bipedalism in ancestrally climbing hominoids.

Assessing the Validity of the Social Impact Scale Among a Longitudinal Cohort of Adolescents and Young Adults Living With Perinatally Acquired HIV.

BACKGROUND: With few psychometrically evaluated HIV-related stigma measures for adolescents and young adults living with HIV, we examined the developmental applicability (ie, validity) of 2 subscales of the commonly used stigma measure, the Social Impact Scale, among a cohort of adolescents and young adults with perinatally acquired HIV. SETTING: Data were obtained from a New York City longitudinal study (N = 340). This study primarily comprised Black and Latinx adolescents and young adults with either perinatally acquired HIV or those with perinatal exposure but who are uninfected. Data for this analysis were obtained from the population with perinatally acquired HIV and spanned approximately a 15-year survey period (2003-2018). METHODS: A confirmatory factor analysis was used at 7 time points to assess whether the Social Rejection and Internalized Shame subscales were consistent in this cohort over time. Overall and individual Cronbach alphas were reported to show the strength of the internal consistency. RESULTS: The mean age from baseline to follow-up 6 ranged from 12 to 23 years over the study period. The Social Rejection subscale was acceptably valid across follow-up periods with strong factor loadings and Cronbach alphas higher than 0.70. However, the Internalized Shame subscale was less valid among younger adolescents. Starting at follow-up 2, we observed better validity with the Internalized Shame subscale performance. CONCLUSION: Future research must consider mechanisms for developing and adapting measures from a developmental perspective to best measure the experiences of HIV-related stigma among younger populations.

Prevalence and Correlates of Intimate Partner Violence Victimization Among Urban Adolescents and Young Adults Living With Perinatally-Acquired HIV Infection or Perinatal HIV Exposure.

INTRODUCTION: Because of privacy and ethical concerns, the data cannot be made available because of the sensitivity of the HIV data and the relatively small sample and ease of identifying people if a few demographics are known.Few studies have examined intimate partner violence (IPV) victimization among adolescents and young adults (AYAs) with perinatally acquired HIV-infection (PHIV) or perinatal HIV exposure without infection (PHEU) in the United States. The purpose of this study was to (1) estimate lifetime and past-year prevalence of IPV victimization and (2) examine correlates of IPV victimization by subtype (physical, psychological, and sexual) and severity (low, moderate, and severe). METHODS: Data came from the sixth interview of an ongoing New York City-based longitudinal study of primarily Black and Latinx AYAPHIV and AYAPHEU. We examined 232 participants (142 PHIV; 90 PHEU) who had reported having been in at least 1 romantic relationship. We used logistic regression models to explore the association between IPV victimization outcomes and select sociodemographic, psychiatric, and environmental factors. Models were adjusted for age, gender, race, ethnicity, and HIV status. RESULTS: IPV victimization prevalence was 84% for lifetime and 65% for the past year. There were no differences in IPV victimization prevalence by PHIV status. Having a recent substance use disorder, reporting higher levels of neighborhood stress, and being male were all positively associated with at least 1 IPV outcome; stronger familial relationships exhibited a protective effect. CONCLUSIONS: The present study suggests that the prevalence of IPV victimization among AYAPHIV and AYAPHEU is exceedingly high that warrants targeted IPV screening and programming for this population.

Identifying the Mental Health Effects of Cumulative Traumatic Exposure in HIV-Affected Youth: A Longitudinal Assessment.

INTRODUCTION: Traumatic events (TEs) in early life can precede adult psychopathology. Limited research exists on this relationship in young adults with perinatally acquired HIV-infection (PHIV) or perinatal HIV-exposure without infection (PHEU), who often experience social and health disparities. This study examined TEs experienced in childhood/adolescence and their association with psychiatric and substance use disorders in young adults with PHIV and PHEU. METHODS: Participants in a New York City-based longitudinal cohort study were assessed for TE exposure at enrollment (mean age = 12 years) and the first 2 follow-up interviews. Past-year psychiatric and substance use disorders were evaluated via psychiatric interview (DISC-IV) at the fifth follow-up interview (mean age = 22 years). Unadjusted and adjusted logistic regression models assessed associations between cumulative childhood/adolescence TEs and young adult psychiatric and substance use outcomes. Group differences were tested for PHIV and PHEU subgroups. RESULTS: Among 236 participants (60% Black, 51% Latinx), mean cumulative traumatic event count was 3.09 (SD = 1.77); 26% had a past-year psychiatric diagnosis, and 28% had a past-year substance use diagnosis. Increased TEs were associated with past-year psychiatric diagnoses in young adulthood [average marginal effects (AME) 4.21, 95% confidence interval (CI): 0.83 to 7.58]; for PHEU participants, increased TEs were associated with a past-year substance use disorder (AME 15.67, 95% CI: 8.08 to 23.25). CONCLUSIONS: High levels of TEs in childhood/adolescence may contribute to psychiatric and substance use disorders in young adults with PHIV or PHEU. Research exploring relationships between TE exposure and later psychiatric problems is needed to inform interventions for HIV-affected youth.

Bilateral Transfer of a Visuomotor Task in Different Workspace Configurations.

Bilateral transfer occurs when a learned behavior transfers from one (group of) effectors(s) to another. Researchers investigating bilateral transfer of a visuomotor adaptation task between limbs used across workspaces have observed divergent results. This study assessed whether bilateral transfer of a visuomotor adaptation task changes with workspace configuration manipulation. Ninety-six right-handed young adults were assigned to one of three workspace locations, i.e., ipsilateral, contralateral, and central. Within each workspace were two retention groups (RRR/LLL) and two bilateral transfer groups (RLR/LRL). Performance before and after training was collected to determine direct and after-effects. We observed an asymmetric transfer of pathlength (left to right) but no ensuing after-effect. However, the transfer of movement time and normalized jerk was symmetric in the contralateral workspace. These findings showed differences in the pattern of bilateral transfer asymmetry in the different workspace configurations, which was parameter specific.

Antibacterial activity of soil-isolated Bacillus altitudinis/pumilus complex against methicillin-resistant Staphylococcus aureus from Mwanza, Tanzania.

Antimicrobial resistance in methicillin-resistant Staphylococcus aureus and beta-lactamase-producing Gram-negative bacteria is a global health concern necessitating research and the development of effective antimicrobial agents. This study, conducted in May 2020 in Mwanza, Tanzania, aimed to determine the antibacterial activity of metabolites from soil-isolated Bacillus species against clinical bacterial pathogens. One soil-isolated Bacillus species, identified as Bacillus altitudinis/pumilus complex, showed antibacterial activity against Gram-positive cocci, including a methicillin-resistant S. aureus strain with inducible clindamycin resistance, previously isolated from a patient with osteomyelitis. Bacillus altitudinis/pumilus complex metabolites may be a potential source of antimicrobial agents against multidrug-resistant bacteria. What this study adds: The study supports existing research on the discovery and development of new antimicrobial agents against multi-drug-resistant bacteria. We report the antimicrobial activity of metabolites extracted from soil-isolated Bacillus altitudinis/pumilus complex strains against Gram-positive bacteria, including a methicillin-resistant Staphylococcus aureus strain with inducible clindamycin resistance.

Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones.

Due to the central role of tubulin in various cellular functions, it is a validated target for anti-cancer therapeutics. However, many of the current tubulin inhibitors are derived from complex natural products and suffer from multidrug resistance, low solubility, toxicity issues, and/or the lack of multi-cancer efficacy. As such, there is a continued need for the discovery and development of new anti-tubulin drugs to enter the pipeline. Herein we report on a group of indole-substituted furanones that were prepared and tested for anti-cancer activity. Molecular docking studies showed positive correlations between favorable binding in the colchicine binding site (CBS) of tubulin and anti-proliferative activity, and the most potent compound was found to inhibit tubulin polymerization. These compounds represent a promising new structural motif in the search for small heterocyclic CBS cancer inhibitors.

Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic. They were randomized 1:1 to an intervention receiving TFV-DP concentration feedback by research staff vs. no feedback at monthly visits for 4 months. Acceptability among medical providers and level of clinical follow-up of TFV-DP results was examined. Patient acceptability was assessed descriptively. Mean electronic adherence (EA), as measured by WisePill device, and TFV-DP in DBS were compared between the two arms. All participants in the intervention group (100%) reported finding TFV-DP feedback helpful and 86% reported changing adherence behaviors. Medical providers indicated high acceptability of incorporating TFV-DP concentration feedback into the clinic, yet among 29 results < 1000 fmol/punch, only 2 were reviewed with no follow-up actions performed. In the intervention arm, mean TFV-DP concentrations were significantly higher (t = 2.5, p < .01) during follow-up and EA in upper quartile (96-100%) was greater compared to controls (x2 = 7.8, p ≤ .05). This study found high acceptability among patients for receiving adherence feedback based on TFV-DP concentrations. TFV-DP and EA data demonstrated greater adherence in the intervention group. Providers indicated high acceptability of incorporating TFV-DP feedback into the clinic, but few providers reviewed results, which could impact clinic-level feasibility.

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

BACKGROUND: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. SETTING: Four primary health clinics in Cape Town, South Africa. METHODS: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. RESULTS: Participants had a median (IQR) age of 34 (27-42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. This relationship was consistent at the time of VB (aOR of 0.41 [95% CI: 0.25 to 0.66] for TFV-DP and aOR of 0.64 [95% CI: 0.54 to 0.76] for EA) and for up to 2 months before VB. Both adherence measures predicted future VB at both 1 month and 2 months before viral load measurement. CONCLUSION: We established that 2 objective adherence measures, EA and TFV-DP in DBS, have a positive association with, and are both strongly predictive of, VB in a community-based South African cohort on ART. Future research is needed to determine the feasibility of implementing these adherence measures in resource-limited settings to facilitate adherence interventions.

Condomless Sex Among HIV-affected AYA in an Era of Undetectable = Untransmittable and Pre-exposure Prophylaxis.

Given poor adherence to treatment and prevention techniques, condomless sex jeopardizes adolescents and young adults (AYA) with perinatally-acquired HIV-infection (PHIV) or perinatal HIV-exposure who are uninfected (PHEU). We examined condomless sex and its association with PHIV-status, psychiatric disorder, and sociodemographics. Data come from a US-based study of primarily Black and Latinx AYAPHIV and AYAPHEU (N = 340). Linear regression models examined condomless sex longitudinally by PHIV-status, psychiatric trajectories, and sociodemographics. Rates of viremia (AYAPHIV) and PrEP use (AYAPHEU) were assessed. 56% of participants reported recent condomless sex, with higher prevalence among: AYAPHEU vs. AYAPHIV (24% vs. 19%, p = 0.017); Latinx vs. non-Latinx AYA (25% vs. 17%, p = 0.014); and AYA with increasing psychiatric comorbidity (44%) and consistent anxiety (23%) vs. low-level disorder (17%; p < 0.05). AYAPHIV had high rates of unsuppressed viral load and AYAPHEU limited PrEP use. Preventing condomless sex is challenging within AYAPHIV and AYAPHEU. Developing accessible combination HIV/mental health interventions is much-needed.

Acceptability and Feasibility of Genetic Testing to Assess Risk of HIV-Associated Neurocognitive Impairment Among Thai Adolescents and Young Adults.

Host genetic factors may modify the risk of developing HIV-associated neurocognitive impairment (HIV-NCI), and genetic research has the potential to inform novel treatments for HIV-NCI. However, there is a need to better understand the acceptability of genetic testing among distinct populations of people living with HIV at increased risk for HIV-NCI, such as young people living with perinatally acquired HIV (PHIV) in low- and middle-income countries, to gauge the feasibility of genetic research within these populations. This pilot study evaluated the acceptability and feasibility of genetic testing to assess risk of future neurocognitive problems in 50 Thai adolescents and young adults (13-24 years; Meanage = 19.16 [standard deviation = 3.09]; 52% female) with PHIV and demographically similar HIV-negative controls. Participants (25 PHIV; 25 controls) completed a survey assessing acceptability of and concerns about genetic testing and were asked to provide blood samples for genetic testing. Descriptive statistics and blood draw completion rates were produced and calculated. Reported concerns about genetic testing were grouped thematically and tallied. Independent t tests and chi-squares explored demographic differences between participants who reported concerns and peers. Results indicated 46 participants (92%) rated genetic testing as "acceptable" or "completely acceptable." Eight participants (16%) reported concerns about genetic testing. The most common concerns were related to genetic information being shared or misused. Compared with participants without concerns, participants who reported concerns had more years of education and were more likely to have postsecondary schooling. Regarding completion rates, 49 participants (98%) agreed to genetic testing and provided blood samples. Overall, results support the acceptability and feasibility of incorporating genetic testing into research investigating HIV-NCI among adolescents and young adults in Thailand. Findings provide important considerations for planning future genetic studies among young people in Thailand.

Evaluating construct and criterion validity of NeuroScreen in assessing neurocognition among hospitalized Ugandan first-episode psychosis patients.

Introduction: Neurocognitive impairment (NCI) is commonly exhibited among patients experiencing their first episode of psychosis. However, there are few resources in many low-income countries, such as Uganda, that allow for the administration of extensive neurocognitive test batteries for the detection of NCI. NeuroScreen is a brief tablet-based neurocognitive assessment battery that can be administered by all levels of healthcare staff. We examined the validity of NeuroScreen to assess neurocognition and detect NCI in first-episode psychosis (FEP) patients in Uganda. Methods: We enrolled 112 participants FEP patients and matched controls at Butabika Mental Referral Hospital. Each participant completed NeuroScreen and a traditionally administered neurocognitive battery: the MATRIC Consensus Cognitive Battery (MCCB). We examined correlations between participant performance on NeuroScreen and the MCCB. A ROC curve determined sensitivity and specificity of NeuroScreen to detect NCI as determined by MCCB criterion. Results: There was a large, statistically significant correlation between overall performance on NeuroScreen and the MCCB [r(112) = 0.64, p < .001]. Small to large correlations were found between tests in the MCCB and NeuroScreen batteries. The ROC curve of NeuroScreen performance to detect MCCB-defined NCI had an area under curve of 0.80 and optimal sensitivity and specificity of 83 % and 60 %, respectively. Conclusion: There was a moderate positive correlation between overall performance on both batteries. NeuroScreen shows promise as a valid assessment battery to assess neurocognition and detect NCI in FEP patients in Uganda. Further studies of NeuroScreen in healthy individuals and in a range of mental disorders are recommended.

Statistical modeling of hormesis quantities in inverted U-shaped dose-response relationships by reparameterization of a bilogistic model.

Statistical procedures that allow quantitative determination of hormesis features are required for quantitative characterization of hormesis to provide information on the biphasic dose-response phenomenon and its variability. Only a direct estimate of individual effective doses in hormetic dose-response relationships is possible using prior extensions of the bilogistic model of Beckon and coworkers. This study presented further extensions of the model to determine the toxic potency and hormetic dose zone by estimating two effective doses simultaneously. In addition, the extended models allow for partitioning the hormetic dose zone through the dose of maximum stimulation. This study demonstrated a 4-step statistical modeling approach to quantify 20 hormesis quantities. The applicability and challenges of the mathematical procedures are discussed based on a few examples of hormetic dose-response relationships. The syntaxes for the analyses were provided as Appendix to demonstrate its implementation in SAS® statistical software. Given the variability of hormetic dose-responses generated from toxicological studies in many disciplines, the proposed approach cannot apply to all dose-response patterns. However, we hope the proposed extensions could provide versatile statistical tools for quantitatively exploring a variety of biphasic dose-response curves.

HIV and suicide risk across adolescence and young adulthood: an examination of socio-demographic, contextual and psychosocial risk factors for attempted suicide in a longitudinal cohort of ageing adolescents affected by HIV living in the New York City Area.

INTRODUCTION: As children become adolescents and young adults (AYA), their risk for attempting suicide increases dramatically, with chronic health conditions an important risk factor. This study examined correlates of suicidality across development in AYA living with perinatally acquired HIV (AYALPHIV) and those perinatally HIV-exposed but uninfected (AYAPHEU). METHODS: Data come from an ongoing longitudinal New York City-based study (N = 339) with AYALPHIV and AYAPHEU interviewed every 12-18 months from 2003 to 2019 (mean enrolment age = 12 years; current mean age = 27 years). The Diagnostic Interview Schedule for Children (adolescent or young adult version) assessed psychiatric disorders and first-reported suicide attempt. Generalized estimating equations were used to examine associations between first-reported suicide attempt and socio-demographic, contextual and psychosocial correlates measured concurrently across six timepoints. RESULTS: At enrolment, 51% of participants were female, 72% heterosexual, 60% Black and 50% Latinx. Attempted suicide was significantly higher among AYALPHIV (27%, CI 21-33%) compared to AYAPHEU (16%, CI 10-22%), with an OR of 1.74 (CI 1.04-2.92) in a model adjusting for age. For AYALPHIV, anxiety (OR 2.66, CI 1.46-4.85), mood (OR 3.62, CI 1.49-8.81) and behaviour disorders (OR 5.05, CI 2.15-11.87) and past-year arrest (OR 3.05, CI 1.26-7.4), negative life events (OR 1.27, CI 1.11-1.46), city stress (OR 2.28, CI 1.46-3.57), pregnancy (OR 2.28, CI 1.08-4.81) and HIV stigma (OR 2.46, CI 1.27-4.75) were associated with increased odds of attempted suicide, while identifying as heterosexual (OR 0.27, CI 0.14-0.52), higher personal (OR 0.45, CI 0.26-0.80) and family self-concept (OR 0.36, CI 0.22-0.57) were protective. Interactions by HIV status and age were found: substance use was more strongly associated with attempted suicide among AYAPHEU than AYALPHIV, while negative life events and higher religiosity were more strongly associated with increased odds of attempted suicide among AYA ≥ 19 versus ≤ 18 years. CONCLUSIONS: AYALPHIV compared to AYAPHEU faced unique risks for attempted suicide as they age into adulthood, with the highest risk among AYALPHIV experiencing HIV stigma or pregnancy and the highest risk among AYAPHEU with substance use. Assessing for suicide risk and correlates with attention to ageing can inform preventive interventions tailored to meet AYALPHIV and AYAPHEU needs.

Adaptation and construct validity evaluation of a tablet-based, short neuropsychological test battery for use with adolescents and young adults living with HIV in Thailand.

OBJECTIVE: Deficits in neurocognitive functioning are common among adolescents and young adults (AYA) with perinatally acquired HIV (PHIV). Limitations of traditional neuropsychological tests hinder assessment of neurocognition in low- and middle-income countries where most AYA with PHIV reside. Computerized testing could make assessment of neurocognition more accessible in these countries. This study examined a culturally modified NeuroScreen, a tablet-based neurocognitive testing app, for use in Thailand. Construct validity was examined among Thai AYA (13-23 years) with and without PHIV. METHOD: NeuroScreen underwent adaptation including language, content, and usability review by Thai psychologists, AYA, and clinical staff. One hundred Thai AYA (50 PHIV; 50 HIV-uninfected, matched controls) were administered the adapted NeuroScreen and a battery of traditional paper-and-pencil neuropsychological tests. Correlations, mean differences, and proportions with impaired performance were examined across NeuroScreen and the traditional tests. RESULTS: The Thai version of NeuroScreen was deemed understandable and culturally appropriate. A large correlation (.82) between overall performance on the NeuroScreen and traditional batteries was observed. Small-to-large correlations were found between conceptually similar NeuroScreen and traditional tests of processing speed, working memory, motor speed, and executive functioning. Mean test performance differences between AYA with PHIV and controls were similar between test batteries. Both sets of tests identified similar rates of impaired participants. CONCLUSIONS: Results provide support for the acceptability and construct validity of the Thai NeuroScreen tests to assess neurocognition in Thai AYA with PHIV. An easy-to-use tool to assess neurocognition can help Thai providers provide better care for AYA with PHIV. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa.

OBJECTIVES: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH. DESIGN: Prospective observational cohort. METHODS: We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/ml) but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed viral load greater than 400 copies/ml. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit. RESULTS: Participants provided 2944 paired DBS and viral load samples. Median (IQR) age was 34 (27-42) years; median duration on ART at study entry was 11 (4-12) months;78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP 400 fmol/punch or less had an adjusted OR of 16.1 (95% CI: 3.9-67.4; P < 0.001) for developing viral breakthrough 1 month later compared with participants with TFV-DP greater 800 fmol/punch. CONCLUSION: TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.

Impact of HIV on Cognitive Performance in Professional Drivers.

BACKGROUND: The intellectually demanding modern workplace is often dependent on good cognitive health, yet there is little understanding of how neurocognitive dysfunction related to HIV presents in employed individuals working in high-risk vocations such as driving. HIV-associated neurocognitive impairment is also associated with poorer long-term cognitive, health, and employment outcomes. SETTING: This study, set in Cape Town, South Africa, assessed the effects of HIV on neuropsychological test performance in employed male professional drivers. METHOD: We administered a neuropsychological test battery spanning 7 cognitive domains and obtained behavioral data, anthropometry, and medical biomarkers from 3 groups of professional drivers (68 men with HIV, 55 men with cardiovascular risk factors, and 81 controls). We compared the drivers' cognitive profiles and used multiple regression modeling to investigate whether between-group differences persisted after considering potentially confounding sociodemographic and clinical variables (ie, income, home language, depression, and the Framingham risk score). RESULTS: Relative to other study participants, professional drivers with HIV performed significantly more poorly on tests assessing processing speed (P < 0.003) and attention and working memory (P = 0.018). Group membership remained a predictor of cognitive performance after controlling for potential confounders. The cognitive deficits observed in men with HIV were, however, largely characterized as being mild or asymptomatic. Consistent with this characterization, their relatively poor performance on neuropsychological testing did not generalize to self-reported impairment on activities of daily living. CONCLUSION: Drivers with HIV may be at risk of poorer long-term health and employment outcomes. Programs that monitor and support their long-term cognitive health are needed.