BACKGROUND: The HIV-1 reservoir in CD4+ T cells (HR METHODS: This study used bisulphite capture DNA methylation sequencing in CD4+ T cells from the blood of 427 virally suppressed women with HIV to identify differentially methylated sites and regions associated with HR RESULTS: The average total HR CONCLUSIONS: These findings suggest that HIV-1 reservoir is linked to aberrant DNA methylation in CD4+ T cells, offering new insights into epigenetic mechanisms of HIV-1 latency and potential molecular targets for eradication strategies. KEY POINTS: Study involved 427 women with HIV. Identified 245 aberrant DNA methylation sites and 85 methylation regions in CD4+ T cells linked to the HIV-1 reservoir. Highlighted genes are involved in viral replication, immune defence, and host genome integration. Findings suggest potential molecular targets for eradication strategies.