The dawn of precision medicine in HIV: state of the art of pharmacotherapy

ABSTRACT

Introduction: Combination antiretroviral therapy (ART) reduces viral load to under the limit of detection, successfully decreasing HIV-related morbidity and mortality. Due to viral mutations, complex drug combinations and different patient response, there is an increasing demand for individualized treatment options for patients.

Areas covered: This review first summarizes the pharmacokinetic and pharmacodynamic profile of clinical first-line drugs, which serves as guidance for antiretroviral precision medicine. Factors which have influential effects on drug efficacy and thus precision medicine are discussed: patients’ pharmacogenetic information, virus mutations, comorbidities, and immune recovery. Furthermore, strategies to improve the application of precision medicine are discussed.

Expert opinion: Precision medicine for ART requires comprehensive information on the drug, virus, and clinical data from the patients. The clinically available genetic tests are a good starting point. To better apply precision medicine, deeper knowledge of drug concentrations, HIV reservoirs, and efficacy associated genes, such as polymorphisms of drug transporters and metabolizing enzymes, are required. With advanced computer-based prediction systems which integrate more comprehensive information on pharmacokinetics, pharmacodynamics, pharmacogenomics, and the clinically relevant information of the patients, precision medicine will lead to better treatment choices and improved disease outcomes.

KEYWORDS:

• Antiretroviral therapy
• pharmacokinetics
• pharmacodynamics
• pharmacogenetic
• precision medicine
• therapeutic monitoring

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Patient and viral genetics can influence pharmacokinetic and pharmacodynamics profiles of first line antiretrovirals.

• There are valuable tools which can be used to promote precision medicine in antiretroviral therapy.

• Precision medicine may allow for targeted use of therapeutic drug monitoring in individuals with HIV.

• Comorbid conditions can influence therapeutic choices and precision medicine may be able to improve outcomes.

This box summarizes key points contained in the article.

Additional information

Funding

The authors acknowledge financial support from the National Institutes of Health with one grant (AA022063) from the National Institute on Alcohol Abuse and Alcoholism and another (DA042374) from the National Institute on Drug Abuse.