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OBJECTIVE: People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown. DESIGN: Cross-sectional study of Thai participants with AHI. METHODS: One hundred and twelve Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II; n = 32) and late (Fiebig III-V; n = 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3 T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups. RESULTS: Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger; P = 0.049) and putamen (19%; P

OBJECTIVE: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach. METHODS: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables. RESULTS: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. CONCLUSIONS: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

The current study applied data-driven methods to identify and explain novel cognitive phenotypes of HIV. Methods: 388 people with HIV (PWH) with an average age of 46 (15.8) and median plasma CD4+ T-cell count of 555 copies/mL (79% virally suppressed) underwent cognitive testing and 3T neuroimaging. Demographics, HIV disease variables, and health comorbidities were recorded within three months of cognitive testing/neuroimaging. Hierarchical clustering was employed to identify cognitive phenotypes followed by ensemble machine learning to delineate the features that determined membership in the cognitive phenotypes. Hierarchical clustering identified five cognitive phenotypes. Cluster 1 (n=97) was comprised of individuals with normative performance on all cognitive tests. The remaining clusters were defined by impairment on action fluency (Cluster 2; n=46); verbal learning/memory (Cluster 3; n=73); action fluency and verbal learning/memory (Cluster 4; n=56); and action fluency, verbal learning/memory, and tests of executive function (Cluster 5; n=114). HIV detectability was most common in Cluster 5. Machine learning revealed that polysubstance use, race, educational attainment, and volumes of the precuneus, cingulate, nucleus accumbens, and thalamus differentiated membership in the normal vs. impaired clusters. The determinants of persistent cognitive impairment among PWH receiving suppressive treatment are multifactorial nature. Viral replication after ART plays a role in the causal pathway, but psychosocial factors (race inequities, substance use) merit increased attention as critical determinants of cognitive impairment in the context of ART. Results underscore the need for comprehensive person-centered interventions that go beyond adherence to patient care to achieve optimal cognitive health among PWH.

People living with HIV (PLWH) residing in high-income countries (HICs) are, in theory, well positioned to benefit from clinical care strategies that predict optimal neurocognitive and neuropsychiatric outcomes. However, there is substantial inter-individual variability in access to clinical care, prevalence of co-occurring risk factors, and comorbid health conditions that represent barriers to achieving the full potential of antiretroviral therapy (ART). Complex interactions between these variables translate into heterogeneity in HIV clinical phenotypes, including abnormalities in brain structure and function. The growing population of PLWH in HICs who are now reaching advanced age introduces additional causal pathways of neurocognitive variability among PLWH receiving ART. These patterns foreshadow trends expected to develop globally in response to increased access to ART. This chapter reviews the combination of highly dimensional risk factors for neurocognitive complications among PLWH residing in HICs. We begin with a brief description of the neuropathological, neuroimaging, and neurocognitive signatures of HIV, followed by a summary of controversies regarding the clinical presentation of HIV-associated neurocognitive disorders (HAND), including putative synergies between HIV disease dynamics and advanced age. Finally, we introduce innovative research strategies that have potential to advance the existing conceptual framework of HAND and, ideally, catalyze the development and of clinical interventions needed to achieve HIV treatment and eradication efforts.

The incidence of traumatic brain injury (TBI) has increased in recent military combat operations due to increased usage of improvised explosive devices as well as better blast survivability from body armor. Sensitive clinical diagnostic tools for mild traumatic brain injury, including structural neuroimaging, are lacking. Further, there is still little known regarding the long term effects of blast TBI on the structure and functioning of the brain. Although many veterans with blast TBI report long term cognitive changes, these diagnostic methods rarely reveal brain changes that corroborate self-reported difficulties. Integrating multimodal neuroimaging may yield more detailed information about the specific sequelae of blast TBI. Functional activation patterns may provide valuable insight into the behavioral characteristics of the brain following blast injury that help explain the origin of lingering cognitive problems reported by veterans. The present study integrated fMRI indices of behavioral activation during an n-back task with resting state metabolic activation using PET in a sample of veterans with mild (n=20) and moderate (n=15) blast TBI and healthy controls (HC) (n=22). Results showed decreased activation of the working memory network in TBI subjects compared to HCs assessed at higher working memory loads. Additionally fMRI based working memory network activation was compared to baseline FDG-PET datasets which revealed an association between functional assessment of the working memory system and baseline metabolism.