Fluctuating Immune Reconstitution and Delayed HIV-1 DNA Decline in People Living with HIV with Low CD4 on Bictegravir-Based Therapy

Abstract

This prospective cohort study compared the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir/lamivudine/efavirenz (TLE) regimens in 88 treatment-naïve persons living with HIV. The BIC regimen achieved faster HIV-1 RNA suppression at week 12, with comparable suppression thereafter. Regarding HIV-1 DNA, the TLE group exhibited a more rapid decline, largely attributable to its higher baseline levels, while both groups converged to comparable levels at week 48; this difference was no longer significant after adjusting for baseline HIV-1 DNA levels. Notably, the BIC group had significantly lower baseline CD4⁺ counts, reflecting the real-world inclusion of individuals with more advanced disease. Cluster analysis within the BIC group revealed three distinct DNA decay trajectories. A subset of individuals with the lowest baseline CD4⁺ counts (Cluster 1, n = 16) showed stable HIV-1 DNA through week 48 followed by significant decline only after 72 weeks, with CD4/CD8 ratio recovery preceding the decline. The early DNA plateau may reflect the interplay between immune reconstitution and viral reservoir dynamics. These findings suggest that baseline immune status influences early viral reservoir dynamics and that the timing of reservoir reduction may be linked to immune restoration, highlighting the heterogeneity of integrase inhibitor responses and the potential value of baseline immune assessment in guiding individualized management.