# Addressing HIV drug resistance research gaps in a cohort of perinatally infected Kenyan children and adolescents

> **NIH NIH R01** · MIRIAM HOSPITAL · 2020 · $967,487

## Abstract

PROJECT SUMMARY
HIV drug resistance may compromise the UNAIDS 90-90-90 treatment goals and is a major hurdle to
sustainable antiretroviral therapy success. Though resistance testing is recommended by guidelines for patient
care in developed countries, there are existing research gaps in its understanding; genotypic-phenotypic
correlations in diverse HIV-1 subtypes, the relationship between minority drug resistance variants and
treatment outcomes, and reasons for discordances between genotype and treatment success or failure remain
unclear. These research gaps are of particular concern in resource-limited settings, where limited medications
and sub-optimal monitoring are common; and in children and adolescents, a vulnerable population with the
need for life-long therapy, who have higher levels of HIV-1 RNA, a wider treatment gap with fewer on therapy,
lower rates of suppression, limited formulations and more non-adherence. The long-term goal of our research
team is to provide new evidence to improve the clinical disease management children and adolescents living
with HIV in resource-limited settings. The purpose of this proposal is to address existing drug resistance
research gaps in a previously established, carefully characterized cohort of 499 children and adolescents living
with HIV in Kenya. To do this, we will use our successful collaboration with the Academic Model Providing
Access to Healthcare (AMPATH) in Kenya, one of the largest HIV programs in sub-Saharan Africa, and
uniquely leverage existing resources from our ongoing R01 AI120792 on perinatally-infected children and
adolescents at AMPATH (MPI Kantor and Vreeman). We hypothesize that comprehensive investigations of
genotypic-phenotypic and resistance-treatment outcome discordances in diverse non-B subtypes will resolve
some of these existing research gaps and optimize patient care in settings where it is most needed. We will
address this hypothesis with the following Aims: (1) Investigate genotype-phenotype correlations; (2) Evaluate
etiologies for treatment failure in the presence of a ‘susceptible genotype’; and (3) Evaluate etiologies for
treatment success in the presence of a ‘resistant genotype’. To achieve these aims, we will use already
available samples (collected between 2016-2018) from the existing cohort of Kenyan children and adolescents
living with non-B subtypes (Aim 1); longitudinally follow the cohort for four years (Aims 2 and 3); collect blood
samples bi-annually and assess adherence; identify participants that are eligible for proposed additional
investigations; conduct in vitro phenotyping to examine genotypic-phenotypic correlations; and perform near
full-length next generation sequencing on RNA and DNA to investigate minority resistance variants and
alternative mechanisms of resistance. The proposal is innovative in the uniqueness of the cohort studied, the
comprehensive proposed scientific investigations, and study design and evaluation of discordant genotype-
...

## Key facts

- **NIH application ID:** 9965742
- **Project number:** 5R01AI147333-02
- **Recipient organization:** MIRIAM HOSPITAL
- **Principal Investigator:** Rami Kantor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $967,487
- **Award type:** 5
- **Project period:** 2019-06-27 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965742

## Citation

> US National Institutes of Health, RePORTER application 9965742, Addressing HIV drug resistance research gaps in a cohort of perinatally infected Kenyan children and adolescents (5R01AI147333-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965742. Licensed CC0.

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