Search

Sub-Saharan Africa, which has about 12% of the global population, is home to almost 70% of individuals infected with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). A recent survey by the Ugandan Ministry of Health has found the HIV prevalence rate to be approximately 7% in sexually active adults. The predominant HIV subtypes present in Uganda are A and D. Health care resources are well planned but often lack human and fiscal resources. Uganda has adopted the World Health Organization (WHO) “3 by 5” global strategy for the introduction of antiretroviral therapy and has surpassed the target. Neurological complications of the HIV virus are common and often have devastating consequences. A recent study in Kampala found the rate of HIV dementia and peripheral neuropathy at 31% and 47%, respectively. Further studies are urgently required to determine the natural history and treatment outcomes of both these common HIV complications. [ABSTRACT FROM AUTHOR]

HIV disproportionately affects Black and Latino people in the United States, but data on longitudinal neurocognitive patterns for these groups are scarce. This study evaluated the incidence and predictors of neurocognitive decline by ethnicity/race in a cohort of Black, Latino, and White people living with HIV (PLWH). Participants included 499 PLWH (43.5% White, 42.7% Black, 13.8% Latino; mean age at baseline = 43.5) from the six-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Participants completed comprehensive neurocognitive and neuromedical evaluations over 3-7 study visits for an average of 2.8 years (SD = 1.1). Interpertation of neurocognitive change was based on published methods using regression-based norms that correct for baseline performance and practice effects. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and predictors of neurocognitive decline. In follow-up, 108 participants (21.6%) declined, 311 (62.3%) remained stable, and 80 (16.0%) improved. In Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latinos compared to Whites (HR = 2.19, 95%CI = 1.32-3.63, p =.002) and Blacks (HR = 1.87, 95%CI = 1.14-3.04, p =.01). Including significant covariates (baseline nadir CD4, hepatitis C Virus, and VACS Index: a composite marker of physical health among PLWH)did not significantly decrease the elevated risk for decline among Latinos. We found that Latino PLWH appear to have higher risk of neurocognitive decline compared to White and Black PLWH. Traditional markers of HIV disease and physical health at baseline did not explain this elevated risk of neurocognitive decline. Future research examining economic, socio-environmental, and culturally-relevant biomedical factors may help to explain this observed ethnic/racial disparity in longitudinal neurocognitive function in HIV. [ABSTRACT FROM AUTHOR]

Presents several abstracts related to neurological disorders. 'HIV-1 Reverse Transcriptase Sequence in Plasma and Cerebrospinal Fluid of Patients With AIDS Dementia Complex Treated With Abacavir,' by E.R. Lanier, G. Sturge, D. McClernon, S. Brown, M. Halman, N. Sacktor, et al published in the 2001 issue of 'AIDS' journal.

Examines the interrelation between AIDS and neurological disorders. Rehabilitation of HIV-related brain impairment; Administration of transdermal selegiline in HIV-associated cognitive impairment; Efficacy of antiretroviral drug therapy for HIV-1 encephalitis.

Abstract Background Among patients with HIV infection, depression is the most frequently observed psychiatric disorder. The presence of depressive symptoms and cognitive dysfunction among HIV patients has not been well studied in Sub-Saharan Africa. Initiation of highly active antiretroviral therapy (HAART) may have an effect on the prevalence and the change over time of depression symptoms and cognitive impairment among HIV-positive individuals. Methods We recruited 102 HIV-positive individuals at risk of cognitive impairment who were initiating HAART and 25 HIV-negative individuals matched for age and education. Depression was assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D). Neurocognitive assessment included the International HIV Dementia Scale (IHDS), an 8 test neuropsychological battery and the Memorial Sloan Kettering scale. Assessments were carried out at 0, 3 and 6 months. Results The HIV-positive group had more respondents with CES-D score > 16 than the HIV-negative group at all 3 clinic visits (54%Vs 28%; 36% Vs 13%; and 30% Vs 24% respectively; all p < 0.050 OR 2.86, 95% CI: 1.03, 7.95, p = 0.044). The HIV positive group had higher likelihood for cognitive impairment (OR 8.88, 95% CI 2.64, 29.89, p < 0.001). A significant decrease in the mean scores on the CES-D (p = 0.002) and IHDS (p = 0.001) occurred more in the HIV-positive group when compared to the HIV-negative group. There was no association between clinical Memorial Sloan Kettering score and depression symptoms (p = 0.310) at baseline. Conclusion Depression symptomatology is distinct and common among cognitively impaired HIV patients. Therefore individuals in HIV care should be screened and treated for depression.

Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years., Methods: PWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor - type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Aβ)-42, soluble amyloid precursor protein-α (sAPPα)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline., Results: Participants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/μL (19,205), current CD4 568/μL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPα). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r ​= ​-0.168, p ​= ​0.0205 and r ​= ​-0.156, p ​= ​0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r ​= ​-0.154, p ​= ​0.0332), while IL-6 did not (r ​= ​-0.109, p ​= ​0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r ​= ​-0.1734, p ​= ​0.0006). Together BDI-II (p ​= ​0.0290), F1 (p ​= ​0.0484) and F3 (p ​= ​0.0309) contributed independently to NC decline (p ​= ​0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression., Conclusions: PWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established., Methods: AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI., Results: In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46-56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P = .02). Baseline frailty however was not associated with NCI development., Conclusions: NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: Distal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized., Methods: This was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates., Results: Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58])., Conclusions: Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Depression is common following HIV infection and often improves after ART initiation. We aimed to identify distinct dimensions of depression that change following ART initiation in persons with HIV (PWH) with minimal comorbidities (e.g., illicit substance use) and no psychiatric medication use. We expected that dimensional changes in improvements in depression would differ across PWH. In an observational cohort in Rakai, Uganda, 312 PWH (51% male; mean age = 35.6 years) completed the Center for Epidemiologic Studies-Depression (CES-D) scale before and up to 2 years after ART initiation. Twenty-two percent were depressed (CES-D scores ≥ 16) pre-ART that decreased to 8% after ART. All CES-D items were used in a latent class analysis to identify subgroups with similar change phenotypes. Two improvement phenotypes were identified: affective-symptom improvement (n = 58, 19%) and mixed-symptom improvement (effort, appetite, irritability; n = 41, 13%). The affect-improvement subgroup improved on the greatest proportion of symptoms (76%). A third subgroup was classified as no-symptom changes (n = 213, 68%) as they showed no difference is symptom manifestation from baseline (93% did not meet depression criteria) to post-ART. Factors associated with subgroup membership in the adjusted regression analysis included pre-ART self-reported functional capacity, CD4 count, underweight BMI, hypertension, female sex(P's < 0.05). In a subset of PWH with CSF, subgroup differences were seen on Aβ-42, IL-13, and IL-12. Findings support that depression generally improves following ART initiation; however, when improvement is seen the patterns of symptom improvement differ across PWH. Further exploration of this heterogeneity and its biological underpinning is needed to evaluate potential therapeutic implications of these differences., (© 2021. Journal of NeuroVirology, Inc.)

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p < 0.001), less likely to be on antiretroviral therapy (p = 0.03), and had higher rates of depression (p < .001) and HIV-associated neurocognitive disorder (p = 0.003). Agreement between physical activity measures was sub-optimal. Prevalence of frailty was high among PWH in rural Uganda, but larger sample sizes and local normative data are needed.

Background: Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions., Design: Longitudinal, natural and treated history of HIV infection among MSM., Methods: The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease., Results: We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time., Conclusion: Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

People with HIV (PWH) taking antiretroviral therapy (ART) have persistent cognitive impairment. The prevalence of cognitive impairment is higher in women with HIV (WWH) compared to men with HIV (MWH), possibly due to sex differences in immune function. Here we report sex differences in cerebrospinal fluid (CSF) immune markers in relation to cognitive performance. A subset of 83 PWH on ART (52% WWH; mean age = 37.6 years, SD = 7.9) from the Rakai community cohort study Cohort and Rakai Health Sciences Program supported clinics in rural Uganda completed a neuropsychological (NP) assessment and a lumbar puncture. CSF was used to measure 16 cytokines/chemokines. Individual NP test z-scores were generated based on local normative data. A series of least absolute shrinkage and selection operator (lasso) regressions examined associations between CSF inflammatory markers and NP outcomes. Overall, there were no sex differences in CSF inflammatory marker levels. However, MWH displayed more associations between inflammatory markers and cognitive performance than WWH. Among MWH, inflammatory markers were associated with a number of cognitive domains, including attention, processing speed, fluency, executive function, learning and memory. MIP-1β, INF-γ, GM-CSF, IL-7 and IL-12p70 were associated with multiple domains. Among WWH, few inflammatory markers were associated cognition. Degree of associations between CSF inflammatory biomarkers and cognitive performance varied by sex in this young, ART-treated, Ugandan cohort. Further investigation into sex-specific inflammatory mechanisms of cognitive impairment among PWH is warranted to inform sex-specific management strategies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Neurological disorders are common in sub-Saharan African, but accurate neuroepidemiologic data are lacking from the region. We assessed a neuroepidemiological screening tool in a rural Ugandan cohort with high HIV prevalence., Methods: Participants were recruited from the Rakai Neurology Study in rural Rakai District, Uganda. A nurse administered the tool and a sociodemographic survey. 100 participants returned for validation examinations by a neurologist (validation cohort). The diagnostic utility and validity of the instrument were calculated and characteristics of those with and without neurological disorders compared., Results: The tool was administered to 392 participants, 48% female, 33% people with HIV, average age 35.1 ± 8.5 years. 33% of the study cohort screened positive for neurologic disorders. These participants were older [mean (SD): 38.3 (9.7) vs. 33.5 (7.1) years, p < 0.001], had a lower Karnofsky score [89.8 (8.4) vs. 93.9 (7.5), p < 0.001] and had a lower body mass index [21.8 (3.3) vs. 22.8 (3.7), p = 0.007] than those who screened negative. Amongst the validation cohort, 54% had a neurological abnormality of which 46% were symptomatic. The tool was 57% sensitive and 74% specific for detecting any neurological abnormality and 80% sensitive and 69% specific for symptomatic abnormalities., Conclusions: We found a lower sensitivity and similar specificity for the screening tool compared with two previous studies. The lower validity in this study was likely due in part to the high percentage of asymptomatic neurological abnormalities detected. This screening tool will require further refinement and cultural contextualization before it can be widely implemented across new populations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is a paucity of information on neurocognitive dysfunction in individuals with HIV in resource-limited regions, despite the fact that these areas have the greatest burden of infection. HIV-associated neurocognitive disorder (HAND) remains a common complication of HIV despite the use of effective antiretroviral therapy (ART). HAND is a major cause of morbidity of HIV+ individuals and is estimated to be the most prevalent form of neurocognitive impairment worldwide in young adults. This finding has drastic implications for the productivity and social engagement of young adults in the development of industry, education, and healthcare, which is particularly relevant in low-income countries. Building an infrastructure to examine the neurological and neuropsychological characteristics of HIV+ individuals in resource-limited settings (RLS) can advance the understanding of the unique contributing factors of HIV-1 clades in these regions of high prevalence, improve neurological monitoring, explore the CNS HIV reservoir, and provide key information on prevention/interventions to help manage/improve these neurological and neuropsychological complications., (© 2019. Springer Nature Switzerland AG.)

Background: With potent antiretroviral therapy and simplified regimens, people living with HIV (PWH) are achieving near-normal lifespans but not necessarily a normal health span or healthy aging. PWH have a higher than expected risk of developing a number of non-AIDS comorbidities, coinfections, and complications (CCC), often against a background of stigma, poverty, and isolation., Setting: To gain a better understanding of research needs for HIV-associated CCC, the NIH convened a 2-day workshop (HIV-associated CCC, or HIV ACTION)., Methods: A cross-institute NIH planning committee identified 6 key research areas: epidemiology and population research, pathogenesis and basic science research, clinical research, implementation science research, syndemics research and international research in low and middle income countries. Investigators were selected to lead working groups (WGs) to assess the state-of-the-art and identify 3-5 priority areas in each field before the workshop. A 2-day program at the NIH was developed which included presentations by invited experts and WG members., Results: Over 400 participants attended the workshop. After general and individual WG discussions, the most pressing gaps, questions, or proposed action items were identified. Priority lists of pressing research issues were presented by cochairs of each WG. A detailed report is posted at the NHLBI website. This article reports the streamlined priority list and a summary of WG discussions to inform investigators of current priorities in the field., Conclusion: Collaborative efforts of many disciplines are needed to improve the health and wellbeing of PWH. Several common themes emerged across WG representing potential priorities for investigators and recommendations for the NIH.

The virology of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the human immune response to the virus are under vigorous investigation. There are now several reports describing neurological symptoms in individuals who develop coronavirus disease 2019 (COVID-19), the syndrome associated with SARS-CoV-2 infection. The prevalence, incidence, and clinical course of these symptoms will become clearer in the coming months and years through epidemiological studies. However, the long-term neurological and cognitive consequence of SARS-CoV-2 infection will remain conjectural for some time and will likely require the creation of cohort studies that include uninfected individuals. Considering the early evidence for neurological involvement in COVID-19 it may prove helpful to compare SARS-CoV-2 with another endemic and neurovirulent virus, human immunodeficiency virus-1 (HIV-1), when designing such cohort studies and when making predictions about neuropsychological outcomes. In this paper, similarities and differences between SARS-CoV-2 and HIV-1 are reviewed, including routes of neuroinvasion, putative mechanisms of neurovirulence, and factors involved in possible long-term neuropsychological sequelae. Application of the knowledge gained from over three decades of neuroHIV research is discussed, with a focus on alerting researchers and clinicians to the challenges in determining the cause of neurocognitive deficits among long-term survivors.

Background: HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda., Methods: Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes., Results: Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD ± 8.5 years) and mean education of 5.4 years (SD ± 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P = 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P < 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance., Conclusions: PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.

Background and Objectives: People with HIV (PWH) often suffer from depressive symptoms which have a deleterious impact on numerous domains including antiretroviral adherence and quality of life. In the general population, a treatment-resistant phenotype of depression is associated with systemic inflammation, which is of considerable importance as it responds favorably to anti-inflammatory medications. Aging PWH experience increasing inflammation. We sought to evaluate the impact of chronic inflammation in aging PWH on depressed mood., Methods: PWH were recruited at 6 U.S. academic medical centers. Depressed mood was assessed using the Beck Depression Inventory (BDI)-II. Inflammatory biomarkers measured at the 12-year follow-up visit in blood plasma using immunoassays were neopterin, sTNFRII, d-dimer, IL-6, CRP, MCP-1, sCD14 and sCD40L. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers., Results: Participants were 78 PWH, 14 (17.9%) women, 40 (51.3%) non-White, mean age 55.3 (±SD 8.29), with a nadir and current CD4 of 134 (IQR 36, 204) and 567 (316, 797), respectively. 80.5% were virally suppressed. A factor analysis of the eight inflammatory biomarkers in plasma at the 12-year follow-up visit yielded 3 Factors, with Factor 1 loading on neopterin and sTNFRII, Factor 2 loading on d-dimer, IL-6 and CRP, and Factor 3 loading on sCD40L (MCP-1 and sCD14 did not appear in any of the factors). Univariate regressions of each factor vs BDI-II scores yielded significance only for Factor 2 (r ​= ​0.295; p ​= ​0.0083 (Bonferroni-adjusted p ​= ​0.0261). Of the Factor 2 component biomarkers, BDI-II scores correlated significantly with d-dimer and IL-6, but not CRP. Women had worse BDI-II scores (p ​= ​0.0127). In a logistic regression with sex and Factor 2, both variables were significant (sex p ​= ​0.0246, Factor 2 p ​= ​0.0168). The relationship between Factor 2 and BDI was significant for men (r ​= ​0.348 [95% CI 0.111, 0.547]; p ​= ​0.0049), but not women (r ​= ​0.0580 95% CI -0.488, 0.571]; p ​= ​0.844). Viral suppression was not significant in the multivariate model., Conclusions: Some PWH with depressed mood have elevated markers of inflammation in blood. Men showed this relationship, while women did not. Together with previous findings that an inflammatory depression phenotype responds to treatment with anti-inflammatory medications, our findings suggest that treatment with anti-inflammatory medications might benefit at least a subset of depressed PWH who have a high inflammatory biomarker profile, as well as poor response to antidepressant medications alone, and that the pathophysiology of depression in men and women with HIV may differ., Competing Interests: The authors report no conflicts of interest, (© 2020 The Authors.)