# Collaborative HIV Investigations of Antiretroviral Neuropsychiatric Toxicities in Zambia (CHANTZ): Protease Inhibitor Impact on Pediatric Cerebrovasculature and Mood

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $232,830

## Abstract

ABSTRACT
Thanks to the widespread availability of antiretroviral therapies (ART), children with vertically acquired HIV can
survive and even thrive, but there remain concerns about the potential effects of long-standing ART usage
particularly when initiated in children in whom a lifetime of treatment is anticipated. Among adults, metabolic
side effects of protease inhibitors (PIs) including insulin resistance, hypertriglyceridemia and elevations in low
density lipoprotein cholesterol are well-established. Whether PIs similarly induce this in children and whether
there is resulting neurovascular compromise is unknown. In adults, vascular insufficiency is a risk factor for
anxiety and depression. Neuropsychiatric adverse events (NP-AEs) such as anxiety and depression are not
typically attributed to PI usage but such effects might be overshadowed in studies by the NP-AEs of efavirenz
used in the same population. If PI-associated metabolic changes result in cerebrovascular insufficiency, this
may be further compromising pre-existing endothelial injury in children mediated by the initial HIV CNS
invasion and localized at autopsy to the basal ganglia and caudate regions. An inflammatory CNS milieu, even
if transient, could further increase the risk of vascular pathology. We propose a model in which PI-induced
metabolic changes result in CNS vasculopathy which contributes to the burden of psychiatric comorbidity in
children with vertically acquired HIV as well as increasing their long-term risk of premature cerebrovascular
disease. To evaluate our model, we will conduct an exposure-control study within a sub-set of Zambian
children presently enrolled in an ongoing study of HIV-associated neurocognitive disorders. Children on a
combined antiretroviral therapy (cART) regimen that includes a PI will be age-matched to children treated with
a cART regimen that does not include a PI and comparisons will be made on metabolic profiles, noninvasive
neurovascular imaging and NP-AEs including anxiety, depression and behavioral disorders.

## Key facts

- **NIH application ID:** 9925503
- **Project number:** 1R21MH122238-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** GRETCHEN L. BIRBECK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $232,830
- **Award type:** 1
- **Project period:** 2020-09-04 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925503

## Citation

> US National Institutes of Health, RePORTER application 9925503, Collaborative HIV Investigations of Antiretroviral Neuropsychiatric Toxicities in Zambia (CHANTZ): Protease Inhibitor Impact on Pediatric Cerebrovasculature and Mood (1R21MH122238-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9925503. Licensed CC0.

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