Antiretroviral therapy intensification in people living with HIV on virological and clinical outcomes: A systematic review

BACKGROUND: Antiretroviral therapy (ART) intensification involves increasing the dose or frequency of existing regimens or adding agents to standard therapy. This systematic review evaluated the impact of ART intensification on selected virological and clinical outcomes among people living with HIV. METHODS: We searched PubMed/MEDLINE, Embase, and Scopus for English-language studies published from database inception to 5 July 2024. Risk of bias was assessed using Cochrane tools. This review was registered by PROSPERO registration: CRD42024565822. RESULTS: Of 1652 identified records, 22 studies met the inclusion criteria. Virological outcomes were heterogeneous, with most strategies showing no significant improvement in viral suppression or HIV reservoir reduction. Neurocognitive outcomes were inconsistent, while immune recovery was observed in some studies. ART intensification was generally safe and well tolerated, although evidence on long-term outcomes remains limited. CONCLUSIONS: There was no consistent evidence supporting a clear benefit of ART intensification on virological or clinical outcomes. ART intensification outcomes vary according to drug selection, patient characteristics, and treatment goals. These findings highlight the uncertainty surrounding the clinical utility of ART intensification. Further research is needed to optimize intensification strategies for specific patient populations and to better define its role in long-term HIV management.