# Immunity and HIV persistence in perinatal HIV infection

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $671,273

## Abstract

Advances in maternal-infant HIV prophylaxis with antiretroviral therapy (ART) have dramatically reduced
mother to child transmission (MTCT), but yearly, >200,000 new vertical HIV infections (HIV+) occur,
predominantly in resource poor nations. With potent early ART initiation, HIV-infected (HIV+) infants can
survive into adulthood. The role and nature of immune mechanisms that are important for HIV reservoir
establishment and mechanisms of HIV persistence in HIV+ infants on ART are poorly understood and may
differ in infants compared to adults. HIV infection stimulates an immune response that can be protective and
have detrimental effects as well. The infant immune system undergoes dynamic developmental changes
and is also challenged by vaccines to stimulate immunologic memory. T follicular helper cells (Tfh) are a
unique subset of CD4 TCM cells that home to germinal centers (GC) in lymph nodes (LN) and facilitates
antibody responses of B cells following vaccination, and this subset has been demonstrated in adults as a
major HIV reservoir. We hypothesize that establishment of HIV reservoirs and HIV persistence in
infancy are influenced by host immune response, timing of ART initiation and events such as
childhood immunizations that stimulate immunologic memory. This proposal will perform
investigations to assess latent and active reservoirs in peripheral blood in the context of a developing
immune system prospectively in HIV+ infants starting ART at age <2 mo. in Maputo, Mozambique.
Peripheral Tfh (pTfh), which are CD4 TCM subset with partial phenotypic and functional similarity to Tfh in LN
will be investigated in infants given childhood vaccines. An older-aged HIV+ Rome cohort, (age 5y-18y) who
started ART within age <1 year, either early (<6mo) or late (7-12mo) and remained consistently aviremic will
provide complementary information about immunity and reservoirs in early versus late treated children after
periods of durable viral control on ART. State-of-art tools including 15 color flow cytometry, RNA
Sequencing, Fluidigm BioMark platform for transcriptomics of fractionated cells and droplet digital PCR for
HIV reservoir are among techniques to be used for three specific aims: 1. To investigate immunologic
biomarkers of HIV reservoirs pre-and post-ART in HIV+ infants starting ART at age <2 mo. and in older-
aged children who started ART at different times <1 year of age. 2. To investigate the effect of childhood
vaccinations on HIV reservoirs in HIV infected infants with early ART initiation and to evaluate their vaccine
responses in comparison with EUI infants; 3. To investigate gene signatures in antigen-stimulated memory
T cells including pTfh post-vaccination to ascertain the relationship between vaccine responses and HIV
reservoirs. The proposed studies could provide insights that build new hypotheses, develop biomarkers of
HIV reservoirs for selecting patients best suited for “cure” related clinical trials, and lead to innovative
thera...

## Key facts

- **NIH application ID:** 9944307
- **Project number:** 5R01AI127347-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Savita Pahwa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $671,273
- **Award type:** 5
- **Project period:** 2016-06-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944307

## Citation

> US National Institutes of Health, RePORTER application 9944307, Immunity and HIV persistence in perinatal HIV infection (5R01AI127347-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944307. Licensed CC0.

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