Abstract
BACKGROUND: Antiretroviral therapy has marked a transformative advancement in the management of people living with human immunodeficiency virus type-1 (HIV-1) (PLWH), converting this disease into a manageable condition. Triple-drug regimens have long been considered the gold standard for treatment. However, recent developments have focused on 2-drug regimens to mitigate the toxicities associated with polypharmacy while maintaining viral suppression and improving patient outcomes. Although the efficacy of treatment simplification is established, the impact on adverse events (AEs) remains unclear. METHODS: To evaluate the relative risk (RR) of developing drug-related AEs (DRAEs), DRAEs leading to treatment discontinuation (DRAEs-LD), and serious AEs, a systematic review and meta-analysis of available phase 3 and 4 clinical trials lasting at least 48 weeks and assessing treatment simplification to oral INSTIs in virologically suppressed PLWH were conducted. The study also evaluated the effects of early (ES) and late (LS) treatment regimen switches. RESULTS: Participants who switched to 2DR exhibited a significantly increased RR of developing DRAEs (RR = 6.92; confidence interval [CI]: 3.02-15.86, P < .001) and DRAES leading to discontinuation (DRAEs-LD) (RR = 4.41; 95% CI: 1.77-10.99; P = .001) compared to those who remained on 3DR/4DR, with no differences observed in the RR of developing serious AEs (RR = 1.06; 95% CI: 0.73-1.55; P = .76). CONCLUSION: Our findings indicate that there is still limited evidence to confirm that treatment simplification to oral INSTIs improves safety and tolerability profiles in the short-mid term. Our analyses emphasize the importance of evaluating symptom burden when considering therapy regimen switches in clinical practice.