# Next generation ultra-long acting antiretroviral formulations for HIV treatment and prevention

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $774,514

## Abstract

Innovations recently introduced into the field of systemic PrEP are long-acting
(LA) formulations of antiretrovirals that stably release drugs over many weeks
either as nanocrystal-based-formulations or intravaginal rings. These approaches
offer major benefits including: (a) the ability to mitigate poor patient compliance
with daily systemic PrEP dosing; (b) the potential for a reduced reliance of HIV
prevention on the front-line HIV therapeutic drugs; and (c) their ability to be
utilized somewhat discreetly without requiring a partner’s knowledge or consent.
In addition, similar advantages have been considered for the use of LA
formulations for HIV therapy. Our long-term goal of this collaborative effort
between Drs. Garcia, Benhabbour, Wahl and Kovarova is to develop a delivery
systems for LA therapy and PrEP that can offer durable and sustained viral
suppression and/or protection from HIV transmission while providing flexibility in
the choice of active ingredient, high efficacy of HIV inhibition and increased user
compliance.
Animal models are essential for the in vivo evaluation of HIV prevention
approaches. Significant progress has been made in the development and
implementation of both non-human primate (NHP) and humanized mouse
models of SIV/HIV infection for the evaluation of topical microbicides, systemic
pre-exposure prophylaxis and HIV treatment. Although both systems have been
shown to provide insight into the process of HIV acquisition and the effectiveness
of different interventions, one notable advantage of using humanized mice is the
ability to use highly relevant transmitted/founder human viruses and human
infected cells for challenge experiments in the presence of human semen. In this
regard, bone marrow/liver/thymus (or BLT) mice have become widely utilized to
evaluate the efficacy of novel prevention approaches and treatment to HIV
infection. Concordant results between humans, NHP and BLT mice when using
the same drug and the same route of challenge (i.e. rectal vs. vaginal) confirm
the suitability of this model for the pre-clinical efficacy evaluation of HIV
prevention and therapy interventions as proposed in the following Specific Aims:
Specific Aim 1) To develop and characterize novel, safe and effective polymer-
based ultra-long acting in-situ forming implants (ISFI) for HIV treatment and
prevention.
Specific Aim 2: In vivo assessment of the efficacy of ultra-long acting EFdA ISFI
formulation to prevent HIV transmission.
Specific Aim 3: In vivo assessment of the efficacy of a combination ultra-long-
acting antiretroviral formulation to control HIV replication in vivo.

## Key facts

- **NIH application ID:** 10228741
- **Project number:** 5R01AI140799-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** J. Victor Garcia-Martinez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $774,514
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228741

## Citation

> US National Institutes of Health, RePORTER application 10228741, Next generation ultra-long acting antiretroviral formulations for HIV treatment and prevention (5R01AI140799-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10228741. Licensed CC0.

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