# Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP)

## TL;DR

This study aims to measure antibiotic concentrations in people living with HIV to improve treatment effectiveness through drug monitoring and dose adjustments.

## Contribution

The study introduces therapeutic drug monitoring for antimicrobial agents in HIV-positive individuals, focusing on optimizing dosing for tuberculosis treatment.

## Key findings

- Antibiotic concentrations will be measured in PLWH using validated analytical methods.
- Dose adjustments based on drug monitoring will be tested for TB treatment in a subset of participants.

## Abstract

Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like
Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB.

The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis

This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection.

TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models.

This study was reviewed and approved by the research and ethics committee in February 2024. Enrolment is projected to begin by August 2024.

We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH).

The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024,
pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764

Antimicrobial resistance is on the increase and people living with HIV may be at increased risk for this, including those living with HIV due to interactions between antiretroviral and antibiotics. There is scarce data about the concentrations of the commonly used antibiotics in the blood of people living with HIV. Monitoring the drug concentrations and adjusting the dose when needed has been recommended in people living with HIV who develop TB. The main objectives of this study are to determine the concentrations of selected antibiotics in people living with HIV and to assess how useful it is to monitor the amount of the antibiotics in blood while adjusting the dose. This study will enroll adults living with HIV receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured, and for those on TB drugs, doses will be adjusted until the participant achieves suitable amounts of the drug in blood. This study was reviewed and approved by the research and ethics committee and we anticipate that the findings from this research will help us to know how much of the antibiotics is in the body and if people respond as expected to the treatment.