# Evaluation of the Impact of HIV Status on the Immune Response to mRNA COVID-19 Vaccines

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $201,875

## Abstract

PROJECT SUMMARY/ ABSTRACT
 At this point in the COVID-19 pandemic, with vaccine roll-out ongoing, one of the most urgent questions
facing people living with HIV (PLWH) and their providers is whether HIV modulates the immune response to
and subsequent effectiveness of the SARS-CoV-2 vaccines. Unfortunately, phase 3 trials for all three of the
U.S.-authorized vaccines did not report HIV specific data and/or did not include enough PLWH to examine the
impact of HIV infection on vaccine efficacy.
 PLWH might plausibly experience a less durable SARS-CoV-2 specific neutralizing antibody (NAb) response
to a SARS-CoV-2 vaccine, as has been seen in response to vaccines for other infections. This lack of durable
NAb responses may be mediated by inflammatory state of HIV infection that persists despite adequate
suppressive antiretroviral therapy (ART), T cell exhaustion, and/or lower CD4/CD8 ratios. Our preliminary work
in the UCSF Long-term Impact of Infection with Novel Coronavirus (LIINC) COVID-19 recovery study has
demonstrated waning antibody responses but stable CD4+ and CD8+ T cell responses among HIV-negative
individuals recovering from natural SARS-CoV-2 infection. However, surrogate virus neutralization titers and
IgG concentrations were lower among PLWH compared to adults without HIV following mRNA vaccination,
raising concerns that PLWH might have a diminished humoral response to vaccination. Whether PLWH mount
less durable humoral and cell-mediated immune responses to COVID-19 vaccines than those without HIV is
largely unknown, including the mechanisms of these differences, although this information could inform clinical
strategies, including additional boosters or safety measures after vaccination.
 This proposal will answer two vital questions about the response to vaccination among PLWH. Aim 1
will provide novel, urgently needed insights into how the SARS-CoV-2 neutralizing antibody response to a
cultured B.1.617.2 (delta) variant, IgG concentration, and antibody magnitude and durability could differ by HIV
status over time following mRNA-based SARS-CoV-2 vaccination, including following boosters. Aim 2 will
examine T cell memory responses and germinal center development generated by mRNA-based SARS-CoV-2
vaccination among PLWH compared to those without HIV out to a year following vaccination. Harnessing, the
research infrastructure of the UCSF CFAR, the LIINC study, and a large, aging population of PLWH
served by the Ward 86 clinic, this analysis will leverage an ongoing cohort to address whether PLWH mount
attenuated immune responses to COVID-19 vaccines. Such data will inform clinical and public health
responses, including the need for additional vaccine doses or safety strategies for PLWH during COVID-19.

## Key facts

- **NIH application ID:** 10481408
- **Project number:** 1R21AI167648-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Monica Gandhi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481408

## Citation

> US National Institutes of Health, RePORTER application 10481408, Evaluation of the Impact of HIV Status on the Immune Response to mRNA COVID-19 Vaccines (1R21AI167648-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10481408. Licensed CC0.

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