Persons With HIV Research Articles

Neuropsychiatric predictors of cognitive functioning over a one-year follow-up period in HIV

BackgroundNeuropsychiatric symptoms (NPS) and cognitive impairment are highly prevalent among persons with HIV (PWH). We examined the effect of the most common NPS, depression and anxiety, on cognitive change among PWH and compared these associations to those among persons without HIV (PWoH). MethodsParticipants included 168 PWH and 91 PWoH who completed baseline self-report measures of depression (Beck Depression Inventory-II) and anxiety (Profile of Mood States [POMS] – Tension-anxiety subscale) and completed a comprehensive neurocognitive evaluation at baseline and at 1-year follow-up. Demographically-corrected scores from 15 neurocognitive tests were used to calculate global and domain-specific T-scores. Linear mixed-effects models examined the effect of depression and anxiety and their interaction with HIV-serostatus and time on global T-scores. ResultsThere were significant depression-by-HIV and anxiety-by-HIV interactions on global T-scores such that, among PWH only, greater depressive and anxiety symptoms at baseline related to worse global T-scores across visits. Non-significant interactions with time suggest stability in these relationships across visits. Follow-up analyses examining cognitive domains revealed that both the depression-by-HIV and the anxiety-by-HIV interactions were driven by learning and recall. LimitationsFollow-up was limited to one-year and there were fewer PWoH than PWH, creating a differential in statistical power. ConclusionFindings suggest that anxiety and depression have stronger links to worse cognitive functioning in PWH than PWoH, particularly learning and memory, and that these associations seem to persist for at least one-year.

Reactivity of Health-Related Quality of Life to Perceived Stress: The Buffering Role of Psychosocial Resources in a Longitudinal Study of Adults with and Without HIV

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.

Intersectional Discrimination in HIV Healthcare Settings Among Persons with Diagnosed HIV in the United States, Medical Monitoring Project, 2018-2019.

Experiences with stigma and discrimination in healthcare settings are associated with negative health outcome for persons with HIV (PWH). PWH may experience discrimination due to the intersection of multiple marginalized social identities. Describing these experiences is important for informing interventions and strategies to reduce stigma and discrimination. We report experiences with discrimination in HIV healthcare settings attributed to multiple characteristics, e.g., sexual orientation, race/ethnicity, income, or social class, and/or injection drug use, among a nationally representative sample of persons with diagnosed HIV in the United States using data from the Medical Monitoring Project (MMP). We calculated weighted prevalences and associated 95% confidence intervals for any discrimination and discrimination attributed to multiple characteristics (intersectional discrimination). Among those experiencing discrimination, nearly 1 in 4 persons reported intersectional discrimination, with a higher burden among key populations of focus for HIV prevention and treatment. Discrimination was attributed to HIV status (62.5%), sexual orientation (60.4%), and race/ethnicity (54.3%). Persons who experienced intersectional discrimination were less likely to have a regular HIV care provider, have trust in HIV care or treatment information from healthcare providers, and be antiretroviral treatment or HIV care visit adherent. Future studies should explore methods to operationalize and assess experiences with intersectional stigma and discrimination and use the outcomes to inform qualitative research that provides more context and a deeper understanding of experiences with intersectional discrimination among PWH.

Comparison of healthspan-related indicators between adults with and without HIV infection aged 18–59 in the United States: a secondary analysis of NAHNES 1999–March 2020

BackgroundAs persons with HIV (PWH) live longer they may experience a heightened burden of poor health. However, few studies have characterized the multi-dimentional health of PWH. Thus, we aimed to identify the extent and pattern of health disparities, both within HIV infection status and across age (or sex) specific groups.MethodsWe used cross-sectional data from the US National Health and Nutrition Examination Survey, 1999–March 2020. The adjusted prevalence of six healthspan-related indicators—physical frailty, activities of daily living (ADL) disability, mobility disability, depression, multimorbidity, and all-cause death—was evaluated. Logistic regression and Cox proportional hazards analyses were used to investigate associations between HIV status and healthspan-related indicators, with adjustment for individual-level demographic characteristics and risk behaviors.ResultsThe analytic sample consisted of 33 200 adults (170 (0.51%) were PWH) aged 18–59 years in the United States. The mean (interquartile range) age was 35.1 (25.0–44.0) years, and 49.4% were male. PWH had higher adjusted prevalences for all of the 6 healthspan-related indicators, as compared to those without HIV, ranged from 17.4% (95% CI: 17.4%, 17.5%) vs. 2.7% (95%CI: 2.7%, 2.7%) for all-cause mortality, to 84.3% (95% CI: 84.0%, 84.5%) vs. 69.8% (95%CI: 69.7%, 69.8%) for mobility disability. While the prevalence difference was largest in ADL disability (23.4% (95% CI: 23.2%, 23.7%); P < 0.001), and least in multimorbidity (6.9% (95% CI: 6.8%, 7.0%); P < 0.001). Generally, the differences in prevalence by HIV status were greater in 50–59 years group than those in 18–29 group. Males with HIV suffered higher prevalence of depression and multimorbidity, while females with HIV were more vulnerable to functional limitation and disabilities. HIV infection was associated with higher odds for 3 of the 6 healthspan-related indicators after fully adjusted, such as physical frailty and depression. Sensitivity analyses did not change the health differences between adults with and without HIV infection.ConclusionsIn a large sample of U.S. community-dwelling adults, by identifying the extent and pattern of health disparities, we characterized the multi-dimentional health of PWHs, providing important public health implications for public policy that aims to improve health of persons with HIV and further reduce these disparities.

Apathy Among Persons Living With HIV Is Associated With Lower Self-efficacy for Health Care Provider Interactions.

Apathy is common in persons with HIV (PWH) and has been associated with a variety of health outcomes. We examined the association between apathy and self-efficacy for health care provider interactions in 142 PWH. A composite score comprised of the apathy subscale of the Frontal Systems Behavioral Scale and the vigor-activation scale of the Profile of Mood States was used to measure apathy. Self-efficacy for health care provider interactions was measured using the Beliefs Related to Medication Adherence - Dealing with Health Professional subscale. Higher levels of apathy were associated with lower self-efficacy for health care provider interactions at a medium effect size, independent of mood disorders, health literacy, and neurocognition. Findings suggest that apathy plays a unique role in self-efficacy for health care provider interactions and support the importance of assessment and management of apathy to maximize health outcomes among PWH.

The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment.

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%). Prevalence estimates of neurocognitive disorder among PWH range from 25 to over 47% - depending upon the definition used (which is currently evolving), the size of the test battery employed, and the demographic and HIV disease characteristics of the participants included, such as age range and sex distribution. Both major depressive disorder and neurocognitive disorder also result in substantial morbidity and premature mortality. However, though anticipated to be relatively common, the comorbidity of these two disorders in PWH has not been formally studied. This is partly due to the clinical overlap of the neurocognitive symptoms of these two disorders. Both also share neurobehavioral aspects - particularly apathy - as well as an increased risk for non-adherence to antiretroviral therapy. Shared pathophysiological mechanisms potentially explain these intersecting phenotypes, including neuroinflammatory, vascular, and microbiomic, as well as neuroendocrine/neurotransmitter dynamic mechanisms. Treatment of either disorder affects the other with respect to symptom reduction as well as medication toxicity. We present a unified model for the comorbidity based upon deficits in dopaminergic transmission that occur in both major depressive disorder and HIV-associated neurocognitive disorder. Specific treatments for the comorbidity that decrease neuroinflammation and/or restore associated deficits in dopaminergic transmission may be indicated and merit study.

Safety and tolerability of adjunctive linezolid with high or standard dose rifampin for the treatment of adults with HIV-associated tuberculous meningitis in Uganda: preliminary findings from the ALTER trial (S25.003)

<h3>Objective:</h3> To analyze preliminary safety data from the <b>A</b>djunctive <b>L</b>inezolid for the <b>T</b>reatment of Tub<b>ER</b>culous Meningitis (ALTER) trial, a phase II trial of high or standard-dose rifampin with or without linezolid 1200 mg for the first 4 weeks of treatment on a backbone of isoniazid, pyrazinamide, and ethambutol. <h3>Background:</h3> Better treatments are needed for tuberculous meningitis (TBM), which leads to mortality in excess of 50%. Linezolid penetrates into cerebrospinal fluid and is effective against TB. Little is known about its use in often critically ill TBM patients. <h3>Design/Methods:</h3> Persons with HIV (PWH) with definite or suspected TBM were recruited from a rural hospital in southwestern Uganda. Participants were seen on day 2, weeks 1, 2, 4, 8, 12, 18, and 24 for symptom assessment, medication adherence, physical examination, visual testing, neuropathy screening, and/or safety labs. <h3>Results:</h3> Of 23 participants enrolled (52% women, mean age 37 years, 78% with moderate to severe TBM grade), 12 were allocated to linezolid. Median CD4 count was 150 cells/mm³, (IQR 81–331) and 7 were on anti-retroviral therapy (ART). Twelve serious adverse events (SAEs) occurred, 6 among those on linezolid. The six included, sepsis (n=2), aspiration pneumonia (n=1), ART-related Stevens-Johnson syndrome (n=1), dehydration (n=1), and hyponatremia (n=1). Seven participants died, 2 on linezolid. No SAE was determined to be related to linezolid. No participants required linezolid discontinuation or dose reduction. Three participants developed ≥grade 3 hyponatremia. No ≥grade 3 anemia, thrombocytopenia, or neutropenia occurred. Mild grade 1 or 2 neuropathy symptoms were reported, more commonly among linezolid recipients (55% versus 0%, p=0.025), but resolved after treatment ended. <h3>Conclusions:</h3> In this preliminary analysis, linezolid was generally safe and well tolerated in TBM patients. Data from the completed trial will increase the power to determine if linezolid is safe to use with high and standard dose rifampin in PWH and TBM. <b>Disclosure:</b> Dr. Kibengo has nothing to disclose. Dr. Kabarambi has nothing to disclose. Mr. Kafeero has nothing to disclose. Dr. Patrick has nothing to disclose. Dr. NAKIMBUGWE has nothing to disclose. Mr. Ssemaganda has nothing to disclose. Mr. Tayebwa has nothing to disclose. The institution of Dr. Nahid has received research support from NIH . The institution of Fiona Cresswell has received research support from Janssen. Dr. Chow has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Medicolegal consulting. The institution of Dr. Chow has received research support from NIH.

The relationship between reincarceration and treatment of opioid use disorder with extended-release naltrexone among persons with HIV

BackgroundIn the United States, a disproportionate number of persons with HIV (PWH) and opioid use disorder (OUD) are involved in the justice system. Medications for OUD (MOUD) can reduce convictions and incarceration time in persons with OUD. Extended-release naltrexone (XR-NTX) has been shown to reduce craving of opioids, recurrence of use, and overdose and help achieve or maintain HIV viral suppression in PWH with OUD involved with the justice system. ObjectivesThis retrospective study aimed to describe factors associated with reincarceration and to evaluate if XR-NTX was associated with reduced reincarceration among PWH and OUD who were released to the community from incarceration. MethodsData from participants released to the community from incarceration from a completed randomized controlled trial was analyzed using a generalized linear model to estimate odds ratios associated with reincarceration and a Kaplan-Meier survival analysis to determine time to reincarceration and non-reincarcerated individuals were compared. ResultsOf the 77 participants, 41 (53.2%) were reincarcerated during the 12-month study period. The mean time to reincarceration was 190 days (SD=108.3). Compared with participants who remained in the community, reincarcerated participants were more likely to have major depressive disorder at study baseline, increased opioid cravings, longer mean lifetime incarceration, and a higher physical quality of life score. XR-NTX was not significantly associated statistically with reincarceration in this analysis. ConclusionReducing reincarceration is a public health priority, given the high proportion of PWH and OUD in the U.S. justice system as well as high degrees of persons returning to the community and having care interrupted due to reincarceration. This analysis determined that potentially identifying depression in recently released individuals could improve HIV outcomes, decrease recurrence of opioid use, and reduce reincarceration.

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.

Evaluation of Statin Prescribing Practices and Predictors of Statin Underutilization in Persons With HIV.

Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared with those without HIV. Despite the increased risk, PWH are less likely to be prescribed statin therapy compared with the general population. The purpose of this study is to describe the statin prescribing practices of an outpatient HIV clinic and identify potential predictors of statin underutilization. This study was a retrospective, single-center chart review of PWH ages 40-79 years receiving care at an HIV clinic. Statin eligibility, statin prescribing practices, and appropriateness of statin therapy were evaluated. Logistical regression analyses were conducted to assess for predictors of underutilization of statin therapy. Of the 606 patients, statin therapy was indicated in 362 patients (60%). Among those with a statin indication, 60.2% were prescribed appropriate statin therapy, 11.6% were prescribed statin therapy but not at the indicated intensity, and 28.2% were not prescribed statin therapy. Tobacco use ( P = 0.0023) was identified as a predictor of statin underutilization. The odds of statin prescribing were higher for those with clinical atherosclerotic CVD ( P = 0.004) and hypertension ( P = 0.017). Statin underutilization was significantly higher in PWH smoking tobacco and PWH without atherosclerotic CVD or low-density lipoprotein-cholesterol 190 mg/dL or higher. In addition, this study highlights the need for more robust CVD prevention efforts in PWH. Identifying predictors of statin underutilization may aid in elucidating where gaps in cardiovascular prevention care may exist.

Isolating the Effect of COVID-19-Related Disruptions on HIV Diagnoses in the United States in 2020.

Diagnoses of HIV in the United States decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010 and 2019 because changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. We developed 3 methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010 to 2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010 to 2018 to evaluate the accuracy of our methods against surveillance data. There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010 to 2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. The substantial drop in number of previously infected PWH diagnosed in 2020 suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic.

Providing telemedicine services to persons living with HIV in an urban community: a demonstration project

ABSTRACT Although HIV incidence and mortality rates have declined over the past 20 years, HIV health disparities continue to persist among patients living in urban communities. Barriers to proficient health outcomes for persons with HIV (PWH) in urban communities include lack of access to care, resulting from limited transportation or clinic availability. While healthcare systems in rural communities provide telemedicine (TM) services to PWH to eliminate transportation and accessibility barriers, few examples exist regarding TM use for PWH in urban communities. This project’s goal was to increase the provision of healthcare services in an urban setting to PWH, using TM. As guided by “Integration of Healthcare Delivery Service” theories and key principles, we created an integration framework comprised of several simultaneous, overlapping activities to include: (1) capacity building (2) clinical standardization (3) community and patient engagement and (4) evaluation performance and measurements. This paper describes major activities involved with developing, implementing and evaluating a TM program for PWH. We discuss results, challenges, and lessons learned from integrating this program into our existing healthcare system.

Effects of a COVID-19 Public Health Lockdown on Drinking and Health Behavior Among Persons with HIV and with Unhealthy Alcohol use in Uganda

To better understand the impact of Uganda’s initial COVID-19 lockdown on alcohol use, we conducted a cross-sectional survey (August 2020-September 2021) among persons with HIV (PWH) with unhealthy alcohol use (but not receiving an alcohol intervention), enrolled in a trial of incentives to reduce alcohol use and improve isoniazid preventive therapy. We examined associations between bar-based drinking and decreased alcohol use, and decreased alcohol use and health outcomes (antiretroviral therapy [ART] access, ART adherence, missed clinic visits, psychological stress and intimate partner violence), during lockdown. Of 178 adults surveyed whose data was analyzed, (67% male, median age: 40), 82% reported bar-based drinking at trial enrollment; 76% reported decreased alcohol use during lockdown. In a multivariate analysis, bar-based drinking was not associated with greater decreases in alcohol use during lockdown compared to non-bar-based drinking (OR = 0.81, 95% CI: 0.31–2.11), adjusting for age and sex. There was a significant association between decreased alcohol use and increased stress during lockdown (adjusted β = 2.09, 95% CI: 1.07–3.11, P < 0.010), but not other health outcomes.

Self-reported alcohol use versus phosphatidylethanol in behavioral trials: A study of people living with HIV in Tshwane, South Africa.

Accurately quantifying alcohol use among persons with HIV (PWH) is important for validly assessing the efficacy of alcohol reduction interventions. We used data from a randomized controlled trial of an intervention to reduce alcohol use among PWH who were receiving antiretroviral therapy in Tshwane, South Africa. We calculated agreement between self-reported hazardous alcohol use measured by the Alcohol Use Disorders Identification Test (AUDIT; score ≥8) and AUDIT-Consumption (AUDIT-C; score ≥3 for females and ≥4 for males), heavy episodic drinking (HED) in the past 30 days, and heavy drinking in the past 7 days with a gold standard biomarker--phosphatidylethanol (PEth) level (≥50 ng/mL)--among 309 participants. We used multiple logistic regression to assess whether underreporting of hazardous drinking (AUDIT-C vs. PEth) differed by sex, study arm, and assessment time point. Participants' mean age was 40.6 years, 43% were males, and 48% were in the intervention arm. At 6 months, 51% had PEth ≥50 ng/mL, 38% and 76% had scores indicative of hazardous drinking on the AUDIT and AUDIT-C, respectively, 11% reported past 30-day HED, and 13% reported past 7-day heavy drinking. At 6 months, there was low agreement between AUDIT-C scores and past 7-day heavy drinking relative to PEth ≥50 (sensitivities of 83% and 20% and negative predictive values of 62% and 51%, respectively). Underreporting of hazardous drinking at 6 months was associated with sex (OR = 3.504. 95% CI: 1.080 to 11.364), with odds of underreporting being greater for females. Steps should be taken to decrease underreporting of alcohol use in clinical trials.

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.

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. Four primary health clinics in Cape Town, South Africa. 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. 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. 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.

Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to − 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline.Trial registration: NCT00867048 and NCT01797367.

Impaired response of memory Treg to high density lipoproteins is associated with intermediate/high cardiovascular disease risk in persons with HIV.

Cardiovascular disease (CVD) is a leading cause of enhanced morbidity and mortality in persons with HIV (PWH) in the era of highly active antiretroviral therapy (AART). However, the underlying mechanisms are not fully understood. Regulatory T cells (Treg), notably the highly suppressive memory subset, have been shown to limit CVD. Importantly, memory Treg cell numbers remain low in many treated PWH. High density lipoproteins (HDL) also protect from CVD, and we previously found that Treg-HDL interactions reduce oxidative stress in these cells. Here, we evaluated Treg-HDL interactions in PWH and whether they were operative in those higher CVD risk. To do that, we recruited a cohort of PWH with intermediate/high CVD risk (median ASCVD risk score of 13.2%, n=15) or low/borderline risk (median ASCVD risk score of 3.6%, n=14), as well as a group of statins treated PWH with intermediate/high CVD risk (median ASCVD risk score of 12.7%, n=14). We evaluated Treg frequency, phenotype and response to HDL. PWH with Int/High CVD risk had a significantly lower number of memory Treg, but memory Treg were more activated and displayed an inflammatory phenotype, versus those with Low/BL CVD risk. In untreated patients, Treg absolute numbers were negatively correlated with ASCVD score. Although HDL decreased oxidative stress in memory Treg in all subjects, memory Treg from PWH with Int/High CVD risk were significantly less responsive to HDL than those from PWH with Low/BL CVD risk. The level of oxidative stress in memory Treg positively correlated with ASCVD scores. In contrast, plasma HDL from PWH, regardless of CVD risk, retained their anti-oxidative properties, suggesting that the defect in memory Treg response to HDL is intrinsic. Statin treatment partially ameliorated the memory Treg defect. In conclusion, the defective HDL-Treg interactions may contribute to the inflammation-induced increased CVD risk observed in many AART-treated PWH.

CD4/CD8 Ratio During Human Immunodeficiency Virus Treatment: Time for Routine Monitoring?

In the last decade, studies in persons with HIV (PWH) on antiretroviral therapy (ART) have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio reflects increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of the CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cutoff points, associated clinical events, effects of treatments, and how the CD4/CD8 ratio could improve decision making in the clinic. Here, we critically review the literature, identify knowledge gaps, and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.

Closing the gaps in the continuum of depression care for persons with HIV: modeling the impact on viral suppression in the United States.

Depression is prevalent among persons with HIV (PWH) and is associated with poorer adherence and lack of viral load suppression (VLS). When treated for depression, PWH are more likely to stay in HIV care and adhere to medications; however, for many PWH, depression is not adequately diagnosed or treated. We adapted Progression and Transmission of HIV (PATH 3.0), a U.S. agent-based dynamic stochastic simulation model, by incorporating a continuum of depression care and estimating the impact on VLS of an enhanced depression diagnosis and care scenario (EDC). We compared EDC - whereby every PWH is assessed for depression, gets treatment if diagnosed, and of those, half achieve remission - to a status quo scenario (SQ) on VLS. Based on published findings, assumptions for SQ were: 34.7% depressed, 45% diagnosed, 55.3% treated and 33% of treated achieving remission. Compared to PWH without depression, we assumed the probability of being non-virally suppressed increased by 1.57 times for PWH with depression (PWH-D), and by 0.95 times for PWH with remitted depression. There was an average increase of 14.6% (11.5-18.5) in the proportion of PWH-D who achieved VLS in EDC compared to SQ. Among all PWH, there was a 4.7% (3.4-6.0) increase in the proportion who achieved VLS in EDC compared to SQ. Fully diagnosing and adequately treating depression would improve health and quality of life for a substantial proportion of PWH-D and result in a nearly 5% increase in expected rates of VLS in the United States, supporting national prevention goals.

Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy.

Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults. We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI-, HIV-LTBI+, HIV-LTBI-). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors. Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models ( P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants ( P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV-LTBI- ( P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4 + T-cell count and ART duration. Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.