Drug Interactions with Gender-Affirming Hormone Therapy: Focus on Antiretrovirals and Direct Acting Antivirals

ABSTRACT

Introduction

Gender-affirming care may include hormonal therapy to attain desired health outcomes in transgender (trans) individuals. To provide safe, affirming medical care for trans patients, health care providers must identify and manage drug-drug interactions (DDIs) between gender affirming hormonal therapy (GAHT) and other medication therapies.

Areas covered

This review summarizes available data on DDIs between GAHT and antiretrovirals (ARVs) or hepatitis C direct acting antivirals (DAAs). Potential pharmacokinetic and pharmacodynamic DDIs are predicted based on GAHT, ARV, and DAA pharmacology and adverse event profiles. Clinical management strategies are discussed.

Expert opinion

GAHT may be involved in pharmacokinetic and/or pharmacodynamic DDIs. Certain ARV classes (non-nucleoside reverse transcriptase inhibitors, protease inhibitors) may alter GAHT disposition, whereas selected ARVs (unboosted integrase inhibitors, doravirine, or rilpivirine) may have less impact on GAHT. DAAs may interact with GAHT, but the clinical relevance is unclear. ARV- and/or DAA-associated side effects (including depression, cardiovascular disease, hyperlipidemia) are important to consider in the clinical management of trans patients. Clinicians must evaluate potential DDIs and overlapping side effects between ARVs, DAAs and GAHT when providing care for trans patients.

KEYWORDS:

• Androgen blockers
• antiretrovirals
• direct acting antivirals
• drug interactions
• estradiol
• gender-affirming therapy
• transgender care
• hiv
• hepatitis C
• testosterone

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Correction

Article highlights

• Antiretrovirals including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors rilpivirine or doravirine, and unboosted integrase inhibitors, are not expected to have clinically significant effects on gender-affirming hormonal therapy concentrations.

• Non-nucleoside reverse transcriptase inhibitors efavirenz, etravirine, and nevirapine may decrease plasma concentrations of estradiol, cyproterone, 5α-reductase inhibitors, progestogens and testosterone.

• Cobicistat-containing regimens may increase plasma exposure to estradiol, while ritonavir-containing regimens may either increase or decrease exposure to estradiol, and both cobicistat and ritonavir are expected to increase exposure to cyproterone, 5α-reductase inhibitors, progestogens and testosterone.

• Direct acting antiviral therapies for the treatment of hepatitis C virus, including glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, and sofobuvir/velpatasvir/voxilaprevir may theoretically increase estradiol concentrations via inhibition of organic anion transport protein 1B1, but it is unclear whether this occurs to a clinically relevant extent.

• Trans individuals taking GAHT may have an elevated risk for depression, cardiovascular disease, hyperlipidemia, and altered bone mineral density; therefore, ARVs or direct acting antiviral agents with minimal influence on these conditions are recommended.

• Tenofovir disoproxil fumarate is associated with decreased bone mineral density and nephrotoxicity, boosted regimens may increase lipids and abacavir should be avoided in trans patients with other cardiac risk factors.

• Integrase inhibitors and tenofovir alafenamide can cause unwanted weight gain, and efavirenz and some integrase inhibitors may have psychiatric effects.

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Declaration of interest

K. Scarsi reports research grant support paid to her institution for her role as a co-investigator on investigator-initiated protocols supported by Merck and Gilead. A. Tseng has received speaker and consultant honoraria from Merck, ViiV and Abbvie. The authors have no other 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.

Additional information

Funding

This paper was not funded