# ACTION: Study of ACuTe Infections On Novel HIV Prevention Modalities

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $812,941

## Abstract

PROJECT SUMMARY/ABSTRACT
Antiretroviral (ARV) agents for treatment and prevention will be key to Ending the HIV Epidemic. Although oral
pre-exposure prophylaxis (PrEP) is highly effective, new options less dependent on day-to-day adherence are
needed to maximize impact. The era of long-acting PrEP has arrived, with rollout of two new products in 2022.
The dapivirine vaginal ring (DVR), self-inserted monthly, is being implemented in sub-Saharan Africa, and
injectable cabotegravir (CAB), given every 8 weeks, is now approved by the U.S. FDA. Despite the promise of
these modalities to reduce HIV incidence, acute HIV infections (AHI) occur among PrEP users and were seen
in DVR and CAB trials. Potential causes of AHI on PrEP modalities include inadequate ARV adherence/
exposure and resistance to the PrEP agent. As oral and long-acting PrEP are scaled up, 300,000 AHI could
occur among PrEP users in the next 5 years. DVR showed modest efficacy in trials and high ring adherence
will be critical. With high levels of circulating ARV resistance (from ARVs in the same class used for treatment),
DVR could fail to block infection with resistant virus. While CAB efficacy was high in trials, AHI occurred
despite on-time injections and resulted in resistance. Because the same drug classes are being used for HIV
prevention and treatment, resistance from CAB could render U.S. and global first-line antiretroviral therapy
(ART) regimens ineffective. Moreover, CAB levels persist for over 1 year in a pharmacokinetic (PK) tail that
could further increase resistance risk. As DVR and CAB are scaled up, key knowledge gaps must be
addressed: 1) What are causes of AHI on DVR and CAB in rollout settings? 2) What behavioral factors
contribute to DVR/CAB non-adherence prior to AHI? 3) What is the risk of DVR/CAB resistance? 4) What are
subsequent HIV treatment outcomes? This application proposes intensive studies of causes of AHI on DVR
and CAB, leveraging three studies enrolling persons with AHI from large PrEP programs in western Kenya and
the U.S. for sample collection, surveys, interviews, and ART outcomes assessment. Innovative methods will be
deployed to detect drug resistance (next-generation sequencing), identify novel mutations (full-genome
sequencing), retrospectively measure ARV exposure before diagnosis (PK analysis of hair samples cut into
segments reflecting exposure over sequential 2-week intervals), and understand DVR/CAB adherence prior to
AHI and ART adherence (longitudinal mixed methods). The proposed aims are: 1) To determine the causes of
HIV infection among women using DVR in Kenya. 2) To identify the causes of HIV infection among persons
using CAB for prevention in the U.S. 3) To evaluate subsequent outcomes on ART after HIV infection among
persons using PrEP modalities. Collectively, these aims will provide the first and largest analysis of causes of
and outcomes following AHI on DVR and CAB in rollout settings. This study will pave the way to address
cru...

## Key facts

- **NIH application ID:** 10547683
- **Project number:** 1R01AI167753-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Catherine Anne Stimets Koss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $812,941
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10547683

## Citation

> US National Institutes of Health, RePORTER application 10547683, ACTION: Study of ACuTe Infections On Novel HIV Prevention Modalities (1R01AI167753-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10547683. Licensed CC0.

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