Title : Does switching from triple (or Quadruple)-Drug Regimen to Double-Drug Regimen with Oral INSTIs Reduce Drug-Related Adverse Events (DRAEs) and Toxicity in Virologically Suppressed People with HIV? SATISFACTION Study
Abstract:
Background: Triple- or quadruple drug regimens (3 or 4DR) remain the gold standard for HIV treatment. However, there is currently a trend towards a reduction in the number of drugs from 3 or 4DR to double-drug regimens (2DR) based on Integrase Strand Transfer Inhibitors (INSTIs). Switching to 2DR is not based on increased efficacy, as studies suggest non-inferiority of 2DR, but aims to reduce adverse events and long-term toxicity associated with prolonged exposure to current antiretroviral drugs. However, to date, neither clinical trials nor real-world data have confirmed this hypothesis.
This study aims to describe the proportion of DRAEs reported in phase III and IV studies in virologically suppressed people with HIV (PWH) on 3 or 4DR and those who have switched from 3 or 4DR to 2DR with second-generation oral INSTIs at ≥ 48 weeks.
Methods: A systematic literature review was conducted, searching the main databases (PubMed, ClinicalTrials.gov, EU Clinical Trials Register, Cochrane, and Embase) from March 2014 to March 2024 and the main conferences from March 2022 to March 2024. We included phase III clinical trials and phase IV studies evaluating the switch from 3DR or 4DR to 2DR based on oral second-generation INSTIs in virologically suppressed PWH, with ≥ 48 weeks of follow-up.
Results: Nine publications met the inclusion criteria. Eight publications corresponded to three phase III clinical trials (TANGO, SALSA and SWORD) at different follow-up periods and one to a phase IV study (DOLAM), with a 48-week follow-up.
The percentage of DRAEs and DRAEs leading to discontinuation increased in patients who switched to 2DR ([6-20%] and [2-4%], respectively) compared to those who remained in 3DR or 4DR ([0-6%] and [0-1%]) at 48 weeks in all studies analyzed (Figure 1). A similar trend was observed with longer follow-up times. Differences observed in laboratory parameters when switching from 3DR or 4DR to 2DR were not clinically relevant.
Conclusions: Therapy simplification from 3DR or 4DR to 2DR with oral second-generation INSTIs in virologically suppressed PWH at ≥ 48 week did not enhance the safety and tolerability profile compared with 3DR or 4DR continuation, according to data reported in phase III clinical trials and phase IV studies.
Financial support: Gilead Sciences
