HIV-Related Cognitive Impairment of Orphans in Myanmar With Vertically Transmitted HIV Taking Antiretroviral Therapy

Linn, Kyaw; Fay, Alexander; Meddles, Katherine; Isbell, Sara; Lin, Phyo Nay; Thair, Cho; Heaps, Jodi M.; Paul, Robert; Mar, Soe

doi:10.1016/j.pediatrneurol.2015.08.004

Cited by 15 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, a full understanding of the neuropathogeneis of pediatric HIV-1 has not been elucidated (Linn et al 2015). The current literature, however, suggests striking differences in the neuropathogeneis of pediatric HIV-1, in comparison to HIV-1 seropositive adults, which may have significant implications for the development of chronic neurological impairment.…”

Section: Discussionmentioning

confidence: 99%

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

2016

View full text Add to dashboard Cite

Since the advent of combination antiretroviral therapy (cART), pediatric HIV-1 (PHIV) has evolved from a fatal disease to a chronic disease as children perinatally infected with HIV-1 survive into adulthood. The HIV-1 transgenic (Tg) rat, which expresses 7 of the 9 HIV-1 genes constitutively throughout development, was used to model the early development of chronic neurological impairment in PHIV. Male and female Fischer HIV-1 Tg and F344N control rats, sampled from 35 litters, were repeatedly assessed during early development using multiple experimental paradigms, including somatic growth, locomotor activity, cross-modal prepulse inhibition (PPI) and gap-prepulse inhibition (gap-PPI). Later eye opening was observed in HIV-1 Tg animals relative to controls. HIV-1 Tg animals exhibited a shift in the development of locomotor activity implicating alterations in the maturation of the forebrain cholinergic inhibitory system. Alterations in the development of PPI and perceptual sharpening were observed in both auditory and visual PPI as indexed by a relative insensitivity to the dimension of time (ms for ISI; days of age for perceptual sharpening) as a function of the HIV-1 transgene. Presence of the HIV-1 transgene was diagnosed with 97.1% accuracy using auditory and visual PPI measurements from PD 17 and 21. Early selective developmental alterations observed in the HIV-1 Tg rats provide an opportunity for the development of a point-of-care screening tool, which would permit for early diagnosis of PHIV and improve the long-term outcome for children perinatally infected with HIV-1.

show abstract

Section: Discussionmentioning

confidence: 99%

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

2016

View full text Add to dashboard Cite

show abstract

“…Total grey matter volume was calculated by summing all cortical, subcortical and cerebellum grey matter volumes. A priori cortical ROIs (left and right hemisphere postcentral gyrus, precentral gyrus, rostral middle frontal gyrus, superior frontal cortex, and superior parietal cortex) were selected due to their roles in higher-order cognitive functioning, which may be impaired in PHIV youth (Crowell et al, 2014; Hazra et al, 2010; Koekkoek et al, 2008; Linn et al, 2015; Raskino et al, 1999). Quality control and processing of PHIV and uninfected youth were executed with the PING processing portal (Jernigan et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…Youth with perinatally-acquired HIV (PHIV) may show cognitive deficits as well as developmental delay even among those with reconstituted immunologic and virologic status, (Cohen et al, 2014; Crowell et al, 2014; Ene et al, 2014; Koekkoek et al, 2008; Linn et al, 2015; Malee et al, 2016; Martin et al, 2006; Nichols et al, 2016; Nozyce et al, 2006; Redmond et al, 2016; Sherr et al, 2014; Sirois et al, 2016; Smith et al, 2012; Smith and Wilkins, 2015) making PHIV a common infectious cause of perinatally-acquired developmental disability globally (Armstrong et al, 1993; Institute of Medicine, 2001; UNAIDS, 2015). Combination antiretroviral therapy (cART) for children with PHIV has resulted in substantial improvements in health with survival beyond childhood and reductions in morbidity and mortality (Brady et al, 2010; Gona et al, 2006; Hazra et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Early HIV infection, immune activation, and viral persistence (due to suboptimal blood brain barrier penetrance of cART regimen) during a critical period of development may be especially detrimental to developing brains in youth with PHIV (Annunziata, 2003; Churchill et al, 2015; Cohen et al, 2015; Ene et al, 2011; González-Scarano and Martín-García, 2005; Kramer-Hammerle et al, 2005; Linn et al, 2015; Martin et al, 2006; Nesbit and Schwartz, 2002; Sarma et al, 2014; Thompson et al, 2011). Brain development is an extended process that begins prenatally and continues throughout the first two decades of life, with increased sensitivity to experience during the first year of life in pathways responsible for sensory, language and higher order cognitive development (Fox et al, 2010; Tierney and Nelson, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Other studies on grey matter volumes in PHIV do not focus on regional grey matter or substance use or are in PHIV populations with varying clinical characteristics from our cohort (Cohen et al, 2015; Sarma et al, 2014). Since PHIV youth often exhibit global cognitive functioning, working memory, and processing speed deficits (Crowell et al, 2014; Hazra et al, 2010; Koekkoek et al, 2008; Linn et al, 2015; Raskino et al, 1999), we hypothesized that frontal and parietal regions, regions important for higher-order cognitive functioning, would show volume reduction as compared to typically-developing, HIV-unexposed and uninfected youth and smaller volumes would be associated with worse cognitive performance. We also hypothesized that HIV disease severity and substance use would be associated with reduced cortical grey matter volumes among adolescents with PHIV.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

Angeles

Williams

Huo

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age=16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age=16.1 years). PHIV youth had smaller (2.8 – 5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0 – 13.4%; marijuana use: 10.1 – 16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.

show abstract

Neurocognition in Viral Suppressed HIV-Infected Children

Crowell

Malee

2017

Global Virology II - HIV and NeuroAIDS

View full text Add to dashboard Cite

HIV-Related Cognitive Impairment of Orphans in Myanmar With Vertically Transmitted HIV Taking Antiretroviral Therapy

Cited by 15 publications

References 21 publications

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

Selective developmental alterations in The HIV-1 transgenic rat: Opportunities for diagnosis of pediatric HIV-1

Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection: Associations with HIV disease severity, substance use, and cognition

Neurocognition in Viral Suppressed HIV-Infected Children

Contact Info

Product

Resources

About