Virological and immunological outcomes and lipid profiles after switching to two-drug regimens in virologically suppressed HIV-1 infected individuals: a retrospective multicenter cohort study

Real-world data on two-drug antiretroviral regimens (2DRs) for HIV-1 patients remain limited in central China. This study aimed to evaluate virological efficacy, immune reconstitution, and lipid profile changes after switching to simplified 2DRs in virologically suppressed HIV-1-infected individuals. This retrospective multicenter cohort study enrolled 1,466 virologically suppressed HIV-1-infected adults who switched to dolutegravir (DTG)-based or lopinavir/ritonavir (LPV/r)-based 2DRs from 2017 to 2024 across four cities in Henan Province, China. The median follow-up was 2.0 years (maximum 8.9 years). The primary outcome was virological non-suppression, defined as two consecutive plasma VL ≥ 50 copies/mL separated by at least 4 weeks. Secondary outcomes included CD4 + T-cell count changes and lipid profile changes. Kaplan-Meier curves, Cox proportional hazards regression, linear mixed-effects models, and binary logistic regression were used for statistical analyses. During follow-up, 87 participants (5.9%) experienced virological non-suppression, defined as two consecutive VL ≥ 50 copies/mL. Median follow-up was 2.0 years, and only 2.7% of participants were followed for≥5 years. Therefore, estimates beyond 4 years should be regarded only as exploratory findings. CD4 + T-cell counts remained stable with a slow increasing trend during follow-up, and triglyceride levels declined markedly within the first three years, especially among patients switched from LPV/r-containing triple regimens to DTG-based 2DRs. Multivariate regression identified prior virological failure as an independent risk factor for virological non-suppression (HR = 2.061, 95% CI : 1.260–3.371, p = 0.004). Maintenance of pre-switch viral load < 200 copies/mL for≥2 years was an independent protective factor (HR = 0.330, 95% CI : 0.21–0.519, p < 0.001). Prior regimen of 2NRTIs+PIs before switching was also an independent protective factor (HR = 0.583, 95% CI : 0.350–0.971, p = 0.038). Baseline CD4 + T-cell levels and historical regimen types predicted incomplete immune recovery. Compared with LPV/r-based dual therapy, DTG-based 2DRs yielded better immune reconstitution and lipid profiles. Switching to simplified 2DRs maintains stable viral suppression and improves immune and metabolic parameters among treatment-experienced HIV-1 patients. In this observational cohort, DTG-based 2DRs were associated with more favorable lipid profiles and higher CD4 + T-cell counts than LPV/r-based 2DRs; however, these comparisons should be interpreted cautiously because of the marked imbalance between groups.