Switching antiretroviral regimes for the treatment of HIV: safety implications

ABSTRACT

Introduction: There are multiple reasons to switch from a virologically successful antiretroviral regimen. Some of them are related to toxicity. Lately, combination antiretroviral treatment (cART) switches have often been related to drug-drug interactions which may also eventually entail safety issues as well.

Areas covered: The purpose of this review is to analyze causes of switching between virologically successful cART regimes related to safety issues. The most relevant papers were selected and summarized.

Expert opinion: Switching cART has been a popular strategy to address safety issues throughout the antiretroviral era. The myriad of switching studies have paralleled the study and release into clinical practice of new antiretroviral drugs with different and often improved safety profiles. Most of them have been successful in improving antiretroviral toxicity while keeping HIV replication under control. However, it should be taken into account that, whenever a new drug is given, there is a possibility of new drug-related toxicity. Notwithstanding that, an increase in cART switching is foreseen, given the fact that we have a wide antiretroviral drug armamentarium and that people living with HIV are ageing and thus more prone to developing age-related co-morbidities whose therapies may entail new interactions and eventually new toxicities.

KEYWORDS:

• Combination antiretroviral therapy
• switching
• safety
• toxicity
• NNRTI
• NRTI
• PI
• INsTI

Article highlights

• Antiretroviral drug switching has been a popular strategy to address antiretroviral drug toxicity

• Keeping viral replication under control is a sine qua non condition to design a switch from an otherwise virologically successful therapy

• The driving force for switching strategies has been the availability of newer drugs with improved safety profiles

• The availability of new and better tolerated drugs have modified the spectrum of switching from reactive to proactive

• Integrase inhibitors are currently the most used drugs in switching strategies

• To avoid or prevent drug-drug interactions is an increasingly cause to switch virologically successful drugs

This box summarizes key points contained in the article.

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.

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Additional information

Funding

This work has been partially funded by Fondo de Investigaciones Sanitarias (FIS PI13/0796, PI14/0700 and PI14/0063), Ministerio de Sanidad, Politica Social e Igualdad (EC11-293), Programa de Suport als Grups de Recerca AGAUR (2009 SGR 1061), and Red de Investigación en SIDA (RIS RD06/006/0022, RD06/0006/1004, RD012/0017/0014, RD12/0017/0005) and by I Convocatoria de Proyectos de Investigación en VIH y Hepatitis 2013, Fellowship Program Gilead (GLD 1300168). Pere Domingo and Francesc Vidal are supported by grants from the Programa de Intensificación de Investigadores, Instituto de Salud Carlos III (INT12/383, INT13/232, and INT11/240).