Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults.

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

Young adults perinatally infected with HIV perform more poorly on measures of executive functioning and motor speed than ethnically matched healthy controls.

Perinatal HIV is associated with significant neurocognitive morbidities, but few studies have examined cognitive impact of early HIV infection on patients surviving to adulthood. The purpose of this study was to evaluate neurocognitive outcomes among a cohort of perinatally infected young adults. Individuals between the ages of 18 and 24 with perinatal infection were recruited for this cross-sectional study along with similarly aged healthy controls. Participants completed an MRI and brief neuropsychological assessment battery. Multivariate analysis of covariance controlling for age, gender, race/ethnicity, and education was completed to detect differences between the HIV+ and control groups. Multivariable linear regression was performed to assess HIV-associated factors potentially impacting neuropsychological findings among the HIV+ group. Twenty-nine HIV+ young adults and 13 healthy controls were included in the study. After adjusting for age and sociodemographic variables, the HIV+ group scored lower on attention/working memory (Digit Span (p = .008) and Letter-Number Sequencing (p = .038)), set-shifting (DKEFS Trail Making Test Condition 4 (p = .026) and motor speed (DKEFS Trail Making Test Condition 5 (p = .003)). For the HIV+ group, nadir CD4 was associated with better Letter-Number Sequencing score (p = .029) and use of highly active antiretroviral therapy was associated with better performance on Category Fluency (p = .040). After controlling for sociodemographic variables, executive dysfunction persists among young adults with perinatal HIV infection in comparison to controls. Future studies to further elucidate the impact of executive dysfunction on independent living and functional outcomes are indicated.

Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection.

Youth infected with HIV at birth often have sleep disturbances, neurocognitive deficits, and abnormal psychosocial function which are associated with and possibly resulted from elevated blood cytokine levels that may lead to a decreased quality of life. To identify molecular pathways that might be associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected subjects over 18-months for intracellular cytokine levels, sleep patterns and duration of sleep, and neurodevelopmental abilities. HIV infection was significantly associated with alterations of intracellular pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12), sleep factors (total time asleep and daytime sleep patterns), and neurocognitive factors (parent and patient reported problems with socio-emotional, behavioral, and executive functions; working memory-mental fatigue; verbal memory; and sustained concentration and vigilance. By better defining the relationships between HIV infection, sleep disturbances, and poor psychosocial behavior and neurocognition, it may be possible to provide targeted pharmacologic and procedural interventions to improve these debilitating conditions.

HIV-1 effects on neuropsychological performance in a resource-limited country, Zambia.

Zambia has substantially been affected by the HIV/AIDS epidemic with prevalence rates at 14% in a population estimated at 12 million. Yet, the extent of HIV-associated neurocognitive disorders (HAND) in this population remains to be clearly understood. A series of culturally appropriate neuropsychological (NP) assessments [International HIV Dementia Scale (IHDS), Color Trails Test 1 and 2, Grooved pegboard Test, and Time Gait Test] were used to test the effects of HIV on NP performance of HIV seropositive and seronegative individuals. Twenty-two percent HIV positive individuals ARV naïve met the criteria for IHDS-defined NP impairment. Gender significantly influenced the performance on NP tests with females performing more poorly compared to males. Larger studies that will accommodate gender differences and age are necessary to generate appropriate norms in Zambia in order to better assess the prevalence of HAND in the developing country setting.

Neurocognitive outcomes in pediatric HIV.

Cognitive impairment has long been associated with the natural history of HIV among vertically infected children. In children, HIV may have a direct or indirect impact on the developing brain, may lead to global or highly specific consequences, and may be responsible for minor cognitive consequences or, conversely, long-term and severe disability. This differential impact is related to multiple factors that influence the individual expression of the virus in any given child. This review provides an overview of the relevant literature on neurocognitive outcomes for infants, children, and youth vertically infected with HIV, with attention to those factors impacting neurocognitive outcome within a developmental framework. Research findings in both the era preceding and following the introduction of combined therapies are reviewed, since many of the issues identified prior to state-of-the-art treatment currently available in the United States and other developed countries still apply in much of the developing world. Intervention issues and directions for future research are also discussed.