08 Nov Even Treated, HIV-Positive Children Have Ongoing White Matter Brain Damage
MedicalResearch.com: What is the background for this study?
Response: The Children with HIV Early Antiretroviral (CHER) trial, conducted in Cape Town and Soweto, was designed when there was uncertainty whether to start antiretroviral therapy (ART) as soon as HIV was diagnosed (below 12 weeks of age) or to wait until there was evidence of immuno-compromise and disease progression. Also, there were concerns about maintaining adherence, long-term toxicity and also resistance in the setting of few antiretroviral options. Early outcomes showed a decreased risk in childhood mortality in the early treatment arms compared to deferred treatment, becoming standard of care globally.
The CHER cohort is one of the largest and best documented of children receiving ART within the first year of life. Also, age- and community-matched HIV exposed uninfected (HEU) and HIV unexposed (HU) uninfected infants were enrolled in parallel for a linked vaccine study.
We therefore had an amazing opportunity to link with a neurodevelopmental sub-study in participants from Cape Town and apply sophisticated neuroimaging modalities that could link with clinical, virological and immunological characteristics.
MedicalResearch.com: What are the main findings?
Response: At age 7, despite early (before age 2 years) ART and viral load suppression, we continue to observe differences in white matter integrity compared to uninfected children. White matter damage observed at age 5 years persists, with new damage evident. The continued observation of regions with lower fractional anisotropy (FA) and higher mean diffusivity (MD) in HIV infected (HIV+) children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the cortical-spinal tract, compared to HU children, suggesting that HIV/ART exposure in utero and/or ART in infancy has a long-term impact on WM development.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: We find that white matter regions of the brain are still vulnerable to the effects of HIV and/or ART, regardless of early treatment. This is in line with other studies finding that HIV+ children continue to experience developmental delays and cognitive deficits. Insults to white matter may be responsible for some of the delays and/or deficits observed in HIV+ children on ART.
Although HIV+ children on ART, particularly early ART, are healthier than previous generations of children not on treatment, more research is needed to better understand how HIV in conjunction with ART continues to influence the path of healthy brain development.
In addition, we find that uninfected children born to HIV+ mothers reveal differences in white matter properties, which suggests more study is need on how HIV/ART exposure may impact brain development in HEU infants.
Should we identify parts of the brain particularly vulnerable to HIV and/or ART, or how timing of ART affects brain development, this could inform treatment policy, improved drug combinations, and early intervention strategies.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: More work is needed linking alterations in HIV+ children to neuropsychological, behavioral and developmental data. While we observe signs of damage to white matter, without directly linking it to a measurable outcome(s) we can only conjecture about the possible ways in which damage manifests in the developing brain. Our research team will soon be analyzing this data.
MedicalResearch.com: Is there anything else you would like to add?
Response: A limitation of this study is that we were not able to measure inflammation from other infections in these children and this may also have had a role in the findings.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Marcin Jankiewicz, Martha J. Holmes, Paul A. Taylor, Mark F. Cotton, Barbara Laughton, André J. W. van der Kouwe, Ernesta M. Meintjes. White Matter Abnormalities in Children with HIV Infection and Exposure. Frontiers in Neuroanatomy, 2017; 11 DOI: 3389/fnana.2017.00088
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