Clinical considerations when switching antiretroviral therapy

ABSTRACT

Introduction

Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.

Areas covered

The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024.

Expert opinion

New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.

KEYWORDS:

• Adherence
• antiretroviral therapy
• convenience
• HIV
• long-acting
• simplification
• switching

Article highlights

• Switching ART is an important clinical strategy for treating established drug toxicity and avoiding potential adverse effects and drug–drug interactions. This is essential in the context of aging, comorbidities, and polypharmacy in PLWH.

• Currently available antiretroviral drugs and combinations with improved barriers to resistance and safety profile, as well as novel routes of administration, enable clinicians to offer new treatment strategies aimed at improving long-term ART adherence, convenience, and quality of life.

• Before switching ART, clinicians must review the pharmacological history and all previous virological failures and drug resistance (both documented and potential) to select the optimal switching option.

• PLWH with multiple prior virological failures and multiclass drug resistance usually have few treatment options, and switching ART is challenging. However, currently available ARV drugs and combinations offer the possibility of simplifying ART even in some of these difficult-to-treat individuals.

• Long-acting intramuscular cabotegravir plus rilpivirine is the first long-acting ART regimen available and has been approved for switching in PLWH with viral suppression. While subject to limitations, this novel treatment strategy offers opportunities for improving the healthcare of PLWH in terms of empowerment and quality of life.

Declaration of interest

A Imaz has received financial compensation for lectures, consultancy work, and educational activities, as well as funding for research, travel grants, and nonfinancial support from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, Thera Technologies, and ViiV Healthcare. 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.