# Pharmacogenomics of ART adherence and effectiveness in the ALIVE Cohort

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $960,711

## Abstract

We propose a comprehensive investigation into the biological factors influencing antiretroviral therapy (ART)
adherence and subsequent treatment outcomes among people who inject drugs (PWID). The AIDS Linked to
the Intravenous Experience (ALIVE) Cohort, a large (N>5000) prospective community-based cohort of PWID
with available GWAS data ascertained for illicit drug use over 3 decades, provides an ideal platform to examine
the interplay between ART adherence, individual level factors (demographic, sociobehavioral and genetic) and
HIV-related outcomes. This sample is >90% African-American addressing a common race/ethnicity shortcoming
in genomics research.
 In a systematic fashion, we propose to move from large-scale epidemiologic data to examining the
underlying cellular mechanisms of differential ART response. In Aim 1, we will perform high-resolution mass
spectrometry (HRMS) of stored bio-specimens to biologically define ART adherence and illicit drug use in the
cohort and perform an informed-GWAS approach (iGWAS) of impulse control in relation to ART adherence,
controlling for illicit drug use. We will also conduct prospective assessment of delayed discounting to examine
the impact of impulsivity on ART adherence, illicit drug use and HIV-related outcomes. In Aim 2, among HRMS-
confirmed ART-adherent subjects we will investigate the relationship between ART-pharmacogenomic factors
and HIV-related outcomes (CD4 recovery, viral load). In Aim 3, we will sort homogenous sets of naïve and
memory CD4+ cells from adherent ALIVE subjects, who vary on CD4 recovery, for multi-level –omics
assessment (genetic, epigenetic, gene expression). In Aim 4, in a sample of non-adherent HIV+ PWID, we will
carry forward the biomarkers identified in Aims 1-3 to explore if pharmacogenomics risk stratification predicts
treatment outcomes to long-acting injectable antiretroviral (LAARV) treatment.
 This work is novel and innovative for several reasons. While prior work has been done on ART
pharmacogenomics, ALIVE is uniquely positioned to investigate a largely African American sample of PWID. We
will apply novel HRMS methods on >3,200 stored plasma samples to construct amongst the largest cohort
database with biologically-defined ART adherence and illicit drug use measures. We will examine CD4 cell-
specific genomic differences in subjects with differential CD4 recovery. Lastly, we will perform a
pharmacogenomically-informed, first-in-population trial of injectable LAARV in a non-adherent PWID population.
In addition to evaluating feasibility, acceptability and safety of this novel treatment, we will explore if a
pharmacogenomics risk score derived from our earlier work can predict ART responses.

## Key facts

- **NIH application ID:** 9898341
- **Project number:** 5R01DA047064-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Gregory D Kirk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $960,711
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898341

## Citation

> US National Institutes of Health, RePORTER application 9898341, Pharmacogenomics of ART adherence and effectiveness in the ALIVE Cohort (5R01DA047064-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898341. Licensed CC0.

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