# Virologic and pharmacologic determinants of dolutegravir failure in East Africa

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $197,390

## Abstract

PROJECT SUMMARY
Background: In response to rising rates of pre-treatment drug resistance (PDR) and risk of increasing rates of
virologic failure in much of sub-Saharan Africa (SSA), a new affordable first-line antiretroviral therapy (ART)
regimen of tenofovir (TFV), lamivudine (3TC), and dolutegravir, known as TLD, will be implemented widely
throughout the region. Beginning in 2018, TLD will be the preferred first-line regimen both for individuals who
are newly initiating ART and those currently on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based
regimens. Given the scope of this policy, there is a critical responsibility to assess potential threats to the
effectiveness of TLD in this population, such as pre-existing drug resistance to TFV and 3TC. Candidate: I am
an Infectious Diseases specialist and clinical investigator engaged in international HIV research with 1.5 years
of experience living and working as a clinical researcher in southwestern Uganda. I have also completed
introductory didactics in clinical study design and analysis and have studied HIV epidemiology in SSA, leading
to four related publications. My overarching career goal is to become an independent, NIH-funded clinician
scientist with expertise in development and implementation of strategies to optimize the management of HIV
treatment failure and drug resistance in SSA. Training: To achieve research independence, I will require
targeted mentoring and additional training in 1) advanced biostatistical methods for large observational
datasets, 2) HIV genomics and antiretroviral resistance interpretation and analysis, and 3) ART clinical
pharmacology and pharmacologic adherence monitoring. Mentors: My training and research plans will be
overseen by my primary mentor Dr. Mark Siedner, who has extensive mentoring and research experience
conducting clinical studies in Uganda. Drs. Bethany Hedt-Gauthier (biostatistics), Daniel Kuritzkes (HIV drug
resistance), and Jose Castillo-Mancilla (pharmacologic adherence monitoring) will serve as co-mentors to
provide additional focused expertise. I will also receive annual feedback from my Scientific Advisory Board,
which includes Drs. Mwebesa Bwana, Vincent Marconi, Jessica Haberer, and Rochelle Walensky. Research:
With guidance from my team of mentors, I will evaluate the rate and determinants of HIV treatment failure
following the planned implementation of TLD in East Africa through the following specific aims: 1) Compare the
effect of TLD versus efavirenz-based first-line ART on viral suppression in a large cohort from East Africa. 2)
Determine the contributions of pre-existing drug resistance to risk of treatment failure both for people newly
initiating ART with TLD as well as for people switching to TLD from an NNRTI-based regimen. 3) Explore
pharmacologic measures of adherence to distinguish virologic failure on TLD with versus without resistance
using urine TFV levels and TFV-diphosphate in dried blood spots. Through this p...

## Key facts

- **NIH application ID:** 9833494
- **Project number:** 5K23AI143470-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Suzanne McCluskey
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,390
- **Award type:** 5
- **Project period:** 2018-12-10 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833494

## Citation

> US National Institutes of Health, RePORTER application 9833494, Virologic and pharmacologic determinants of dolutegravir failure in East Africa (5K23AI143470-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833494. Licensed CC0.

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