# Long-term clinical and immunologic consequences of inflammation in perinatal HIV

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $756,077

## Abstract

Project Summary
Globally, 2.7 million children are living with HIV and 270,000 new infections occur annually. With antiretroviral
therapy (ART) that suppresses viremia these children are surviving through adolescence into adulthood, but
ART may not fully restore immunologic health and inflammation may persist despite early ART initiation. In adults
living with HIV (ALHIV) inflammation has been associated with higher incidence of cardiovascular, metabolic and
neurocognitive age-related comorbidities than persons without HIV. Because immunologic and neurologic
development occur alongside exposure to HIV and ART in children with perinatal HIV (CPHIV), the long-term
consequences of inflammation may differ from adults and is largely unknown. In a cross-sectional study of
Kenyan CPHIV, we previously reported that inflammation persists despite viral suppression on ART. The
proposed research leverages this cohort in a 10-year follow up study to determine whether viral suppression on
prolonged ART dampens immune activation, the pathogenic mediators of inflammation and the consequences
of sustained inflammation with a global assessment of immunologic, cardiovascular, metabolic and
neurocognitive outcomes. The follow up cohort will include 80 persons with perinatal HIV (PPHIV) on ART for
~11 years and 82 persons unexposed to HIV (HU). In Aim 1, the durability of inflammation and immune
dysregulation in PPHIV on long-term ART with viral suppression will be assessed by comparing monocyte
(sCD14, sCD163), T cell (CD38, HLA-DR) and plasma (hsCRP, TNF-α, IL-6) inflammatory markers and innate
and adaptive immune cell subsets between baseline (T0, 2012 PIA study) and 10-year follow-up (T1) levels. The
pathogenic role of viral reservoir size and replicative capacity and intestinal permeability on immune activation
will also be assessed. In Aim 2 we will examine whether early (T0) or concurrent (T1) inflammatory markers
correlate with clinical outcomes including 1) cardiovascular measures of myocardial function by echocardiogram
and endothelial dysfunction by endothelial peripheral arterial tonometry (EndoPAT), 2) metabolic measures of
insulin resistance by HOMA-IR and pancreatic beta cell function and stress by HOMA-B and proinsulin/C-peptide
ratios and 3) neurocognitive assessments using NeuroScreen, a tablet-based tool that evaluates six
neuropsychological domains most affected by HIV. The proposed study will be among the first to
comprehensively examine multisystemic immunologic, cardiovascular, metabolic and neurocognitive outcomes
in PPHIV in sub-Saharan Africa after prolonged viral suppression. Our research will fill fundamental knowledge
gaps in understanding the role of early childhood inflammation in durable health outcomes of PPHIV, with
potential to identify screening biomarkers and implement preventative interventions that mitigate HIV-related
comorbidities so PPHIV can thrive as adults.

## Key facts

- **NIH application ID:** 10924821
- **Project number:** 1R01HD113487-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Alka Khaitan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $756,077
- **Award type:** 1
- **Project period:** 2024-08-07 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924821

## Citation

> US National Institutes of Health, RePORTER application 10924821, Long-term clinical and immunologic consequences of inflammation in perinatal HIV (1R01HD113487-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10924821. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*