Behavioral disorders are common in persons infected with human immunodeficiency virus (HIV). The differential includes preexisting psychiatric diseases, substance abuse, direct effects of HIV infection, opportunistic infection, and the adverse effects of medical therapies. Many patients have more than one contributing or comorbid problem to explain these behavioral changes. The differential should always include consideration of psychosocial, genetic, and medical causes of disease. Treatment strategies must take into account the coadministration of antiretroviral therapy and the specific neurologic problems common in patients infected with HIV.

Biobanks are storage places for biospecimens that can be used for current and future scientific research. Biospecimens are exceptional sources of biological data that can be potentially translated from molecular and genetic information to clinically relevant treatment modalities. Examples of such biospecimens include, but are not limited to, blood, skin, hair, saliva, stem cells, DNA, and RNA. The volume of biospecimens worldwide continues to grow at an extraordinary rate posing a challenge for biobanks to manage this growth. Due to the vital role of biobanks in research, an understanding of biobanking sustainability is important. Simply starting to collect biospecimens without strategic planning and cost analysis can lead to failure. Components vital to sustainability include fostering public support, cost-effective banking, funding development, standardized protocols, and interoperability.

Objectives

Recent studies suggest that intraindividual variability (IIV) of neuropsychological performance may be sensitive to HIV-associated neurologic compromise. IIV may be particularly dependent upon the integrity of frontal-subcortical systems, and therefore may be a meaningful phenotype in HIV. We examined the relationship between change in IIV and white matter integrity among HIV seropositive (HIV+) and HIV seronegative (HIV-) individuals.

Method

The sample consisted of 38 HIV+ participants and 26 HIV- control participants who underwent neuroimaging and a neuropsychological evaluation at baseline and at 2-year follow-up evaluation.

Results

Among HIV+ participants, increases in IIV (greater dispersion) were related to lower fractional anisotropy (FA) values in the anterior thalamic radiations (ATR) and the superior longitudinal fasciculus (SLF). Changes in mean-level global cognitive functioning were not significantly related to white matter integrity. Additionally, there was a significant Group × IIV interaction effect in the SLF demonstrating that the relationship between IIV and white matter integrity was specific to HIV.

Conclusions

Overall, findings suggest that IIV may be more sensitive, relative to mean-level global cognitive functioning, in the detection of neurologic compromise among HIV+ individuals. (PsycINFO Database Record

The purpose of the current study was to examine the independent and interactive effects of social adversity (SA) and HIV infection on subcortical shape alterations and cognitive functions. Participants included HIV+ (n = 70) and HIV- (n = 23) individuals who underwent MRI, neurocognitive and clinical assessment, in addition to completing questionnaires from which responses were used to create an SA score. Bilateral amygdalae and hippocampi were extracted from T1-weighted images. Parametric statistical analyses were used to compare the radial distance of the structure surface to a median curve to determine the presence of localized shape differences as a function of HIV, SA and their interaction. Next, multiple regression was used to examine the interactive association between HIV and SA with cognitive performance data. An HIV*SA interactive effect was found on the shape of the right amygdala and left hippocampus. Specifically, HIV-infected participants (but not HIV-uninfected controls) who evidenced higher levels of SA displayed an inward deformation of the surface consistent with reduced volume of these structures. We found interactive effects of HIV and SA on learning/memory performance. These results suggest that HIV+ individuals may be more vulnerable to neurological and cognitive changes in the hippocampus and amygdala as a function of SA than HIV- individuals, and that SA indicators of childhood SES and perceived racial discrimination are important components of adversity that are associated with cognitive performance.

The persistence of HIV infection, even after lengthy and successful combined antiretroviral therapy (cART), has precluded an effective cure. The anatomical locations and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. In this study, we review research supporting the importance of anatomical tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages. We present accumulated research that clearly demonstrates the limitations of using blood-derived cells as a proxy for tissue reservoirs and sanctuaries throughout the body. We cite recent studies that have successfully used deep-sequencing strategies to uncover the complexity of HIV infection and the ability of the virus to evolve despite undetectable plasma viral loads. Finally, we suggest new strategies and highlight the importance of tissue banks for future research.

Objective

Mild forms of HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of combination antiretroviral therapy (cART). Although elevated lipopolysaccharide (LPS) and immune activation are implicated in HAND pathogenesis, relationships of LPS and inflammatory markers to mild forms of HAND or impairment in specific cognitive domains are unknown. To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort.

Methods

We analyzed plasma from HIV+ subjects (n = 97) with nadir CD4 counts <300 and high frequency of hepatitis C virus coinfection and illicit drug use for relationships between sCD14, CCL2, and LPS levels and neurocognitive test scores.

Results

Plasma sCD14 levels were higher in subjects with test scores indicating global impairment (P = 0.007), particularly in attention and learning domains (P = 0.015 and P = 0.03, respectively), regardless of HAND diagnosis. Plasma sCD14 levels correlated inversely with global, attention, and learning T scores (P = 0.036, 0.047, and 0.007, respectively) and yielded higher area under receiver operating characteristic values for predicting impaired scores than single-marker models based on plasma or cerebrospinal fluid viral load or CD4 count (area under receiver operating characteristic values = 0.71, 0.81, and 0.71, respectively) and in 4-marker models based on plasma sCD14 and 3 conventional markers compared with the 3-marker models.

Conclusions

Plasma sCD14 is a biomarker associated with impaired neurocognitive testing in attention and learning domains in HIV-infected individuals with advanced disease, suggesting involvement of cortical and limbic pathways by inflammatory processes in the cART era. Plasma sCD14 is a potential biomarker to monitor HAND progression and therapeutic responses.

Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here, we have identified features, routinely collected in primary care settings, that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV individuals.

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Objective

HIV-associated neurocognitive disorder (HAND) occurs in a significant percentage of HIV-infected (HIV+) adults. Increased intraindividual variability (IIV) in cognitive function may be an early marker of emerging neurocognitive disorder, which suggests that IIV may be a sensitive measure of neurologic compromise in HIV. In the current study, we hypothesize that increased IIV may predict impending morbidity, including future cognitive decline and death.

Method

In 708 HIV+ participants followed longitudinally for up to 14 years, we assessed the role of dispersion in forecasting death and cognitive decline. Incident neurocognitive impairment was predicted in a mixed-effects ordinal logistic regression model using age, gender, baseline mean cognitive functioning, CD4+, time followed, years of education, and dispersion at the previous visit. Death before the next visit was predicted in a binomial mixed-effects regression model using age, gender, baseline mean cognitive functioning, CD4+, time followed, years of education, and dispersion.

Results

Point-in-time dispersion and change in dispersion between visits predict future cognitive decline and death in HIV+ individuals. Individuals with greater dispersion at a visit or who had larger changes in dispersion between visits were more likely to demonstrate greater neurocognitive impairment at the subsequent visit. Greater IIV was also associated with an increased risk of death prior to the subsequent visit, even after controlling for HAND severity and global cognitive functioning.

Conclusions

We conclude that the IIV in cognitive functioning may be more predictive of future disease consequence than mean level of cognitive functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein "Nef" can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef-macrophage interaction and how this relationship contributes to disease pathogenesis.