# Acquired HIV drug resistance among Nigerian children failing first-line ART: Implications for second-line dolutegravir use

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $198,211

## Abstract

PROJECT SUMMARY
The accumulation of HIV drug resistance (HIVDR) threatens to erode gains in HIV treatment globally. As a
result, the World Health Organization (WHO) Global Action Plan on HIVDR has called for increased
surveillance. Notably, the 2019 WHO Drug Resistance report included data on the alarming increase in
pretreatment HIV drug resistance (PDR) among adults and infants, as well as data on acquired drug
resistance (ADR) among adults failing first-line ART. However, data on ADR among children is glaringly
absent.
As countries begin to implement 2019 WHO guidance to replace lopinavir/ritonavir- with dolutegravir (DTG)-
based second-line ART among children, data on ADR is even more pertinent. While DTG holds great
promise for improving HIV outcomes and reducing drug resistance given its potency and high barrier to
resistance, its use for second-line ART among patients with pre-existing nucleoside reverse transcriptase
inhibitor (NRTI) resistance is unknown. Failed studies of DTG monotherapy provide a cautionary message
that the NRTI backbone remains important for virologic suppression and preventing integrase resistance.
Nigeria is home to more children living with HIV than any other country in the world. In a national survey of
PDR among ART-naïve infants ≤18 months of age, high rates of resistance were observed, including to the
most widely used NRTI backbone among children (abacavir and lamivudine). However, rates of ADR after
first-line failure are expected to be even higher. Since 2004, APIN Public Health Initiatives has provided HIV
care and treatment to over 20,000 children in Nigeria, and thus is uniquely positioned to provide critical drug
resistance data from multiple pediatric sites/regions across Nigeria. We propose to evaluate ADR among
400 children in Nigeria failing first-line ART, and will utilize these data to derive a clinical prediction rule
(CPR) to identify those most likely to benefit from targeted HIVDR testing and avoid functional DTG
monotherapy. Further, rapid point-of-care (POC) HIVDR testing is needed to address feasibility barriers in
low income settings. We will therefore evaluate the OLA-Simple POC HIVDR assay, which has equivalent
sensitivity to standard sequencing methods, but has not been validated among the unique HIV-1 subtypes
prevalent in Nigeria. This combination of studies addresses a critical gap in knowledge regarding ADR
among children failing first-line ART, will inform future studies of targeted HIVDR testing prior to second-line
switch, and will evaluate a rapid POC HIVDR assay in this setting. This has the potential to impact
international guidance on second-line DTG use and HIVDR testing for this vulnerable population of children.

## Key facts

- **NIH application ID:** 10483175
- **Project number:** 5R21AI162201-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Holly Elizabeth Rawizza
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,211
- **Award type:** 5
- **Project period:** 2021-09-07 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483175

## Citation

> US National Institutes of Health, RePORTER application 10483175, Acquired HIV drug resistance among Nigerian children failing first-line ART: Implications for second-line dolutegravir use (5R21AI162201-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10483175. Licensed CC0.

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