Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa

Hoare, Jacqueline; Fouché, Jean-Paul; Phillips, Nicole; Joska, John A.; Donald, Kirsten A.; Thomas, Kevin G. F.; Stein, Dan J.

doi:10.1007/s13365-014-0311-1

Cited by 53 publications

(44 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Montiero de Almeida et al (de Almeida et al 2013) revealed no significant differences in the frequency of mild, moderate, or severe cognitive impairment between HIV-C and HIV-B. This is consistent with multiple studies conducted in South Africa and India that describe significant cognitive impairment in HIV+ adults and children (Hoare et al 2015a; Joska et al 2011; Yepthomi et al 2006; Gupta et al 2007; Ghate et al 2014). More recently, our group compared cognitive performances between HIV-C individuals with and without the Tat C31S polymorphism and reported no significant differences in the cognitive phenotype or severity of cognitive impairment by Tat status (Paul et al 2014).…”

Section: Introductionsupporting

confidence: 67%

“…The extant literature is replete with evidence of cognitive impairment among children and adults with HIV from regions around the world with high frequency of clade C virus (de Almeida et al 2013; Hoare et al 2015a; Joska et al 2011; Yepthomi et al 2006; Gupta et al 2007; Ghate et al 2014; Paul et al 2014; Hoare et al 2015b). While most of these investigations did not sequence the dicysteine motif of Tat to confirm the presence of cysteine or serine at position 31, the results are consistent with our previous cognitive study in which C31S status was defined (Paul et al 2014).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

et al. 2016

Self Cite

View full text Add to dashboard Cite

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV− controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV− controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV− controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

show abstract

Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lower FA, higher MD and RD in the CC and higher MD in the superior longitudinal fasciculus have been demonstrated in ART-naïve children (8-12 yrs) compared to age-matched controls 13 , while ART failure was associated with decreased FA in the left superior and right posterior corona radiata and decreased AD in the left inferior cerebellar peduncle in 50 children on first line ART (6-15 yrs). 14 Regional and whole brain decreases in FA, and increased MD and RD, compared to controls, have been reported in HIV+ children and adolescents (6-20 years) 15,16 irrespective of treatment status. 15 Regional alterations were related to past disease severity, measured by nadir CD4% and peak viral loads.…”

Section: Introductionmentioning

confidence: 95%

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing

Ackermann¹,

Andronikou

Saleh

et al. 2016

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

Background, purpose Fractional anisotropy in the frontal white matter, corpus callosum and internal capsule are abnormal in HIV+ adults. We describe the distribution, nature of white matter abnormalities in a cohort of children who started ART within the first year of life - and benefit of early treatment using DTI measures (fractional anisotropy, mean, axial and radial diffusion). Materials, methods DTI was performed on children in a neurodevelopmental sub study from the Children with HIV Early Antiretroviral (CHER) trial. Voxel-based group comparisons were performed to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children. Associations of DTI parameters with timing of ART initiation were examined. Results 39 HIV+ children (15 male, mean age 5.4 years) and 13 controls (5 male, mean age 5.7 years) were imaged. 2 Clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group with symmetrical distribution predominantly due to increased radial diffusion, suggestive of decreased myelination. Corticospinal tracts rather than the corpus callosum were predominantly involved. Children on early interrupted ART had lower fractional anisotropy compared to those receiving continuous treatment. Conclusion HIV+ children at 5 years have white matter abnormalities measured by fractional anisotropy, despite early ART, suggesting that early ART does not fully protect the white matter either from peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum, possibly due to early ART. Continuous early ART can limit white matter damage.

show abstract

“…In a series of studies of vertically-infected HIV+ children, a research group in South Africa reported a possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuro-HIV [46]. …”

Section: Introductionmentioning

confidence: 99%

Novel Neuroimaging Methods to Understand How HIV Affects the Brain

Thompson

Jahanshad

2015

Curr HIV/AIDS Rep

View full text Add to dashboard Cite

In much of the developed world, the HIV epidemic has largely been controlled by anti-retroviral treatment. Even so, there is growing concern that HIV-infected individuals may be at risk for accelerated brain aging, and a range of cognitive impairments. What promotes or resists these changes is largely unknown. There is also interest in discovering factors that promote resilience to HIV, and combat its adverse effects in children. Here we review recent developments in brain imaging that reveal how the virus affects the brain. We relate these brain changes to changes in blood markers, cognitive function, and other patient outcomes or symptoms, such as apathy or neuropathic pain. We focus on new and emerging techniques, including new variants of brain MRI. Diffusion tensor imaging, for example, can map the brain’s structural connections while fMRI can uncover functional connections. Finally, we suggest how large-scale global research alliances, such as ENIGMA, may resolve controversies over effects where evidence is now lacking. These efforts pool scans from tens of thousands of individuals, and offer a source of power not previously imaginable for brain imaging studies.

show abstract

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa

Cited by 53 publications

References 37 publications

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity

Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing

Novel Neuroimaging Methods to Understand How HIV Affects the Brain

Contact Info

Product

Resources

About