Comparative Metabolic Effects of Integrase Inhibitor and Emtricitabine-Containing Tenofovir Derivatives in People Living with HIV: A Multi-Center Retrospective Analysis

Abstract Background This retrospective, multi-center cohort study aimed to compare the effects of Integrase Strand Transfer Inhibitor (INSTI) based therapies containing tenofovir disoproxil fumarate (TDF)/ Emstristabin (FTC) /Dolutegravir (DTG), TDF/FTC/Cobicistat (C)/Elvitegravir(EVG), TDF/FTC/Raltegravir (RAL) and tenofovir alafenamide (TAF)/FTC/Bictegravir (BIC), TAF/FTC/c/EVG) combinations on bone metabolism, lipid profile, and renal function in people living with HIV (PLWH). Methods Adults aged ≥ 18 years receiving antiretroviral therapy (ART) for ≥ 12 months were followed for ≥ 24 months. Data were obtained from HIV/AIDS clinic records and hospital databases, including demographics, laboratory values (HIV RNA, CD4 + T lymphocyte count, creatinine, eGFR, ALT), lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides), and DEXA results. Statistical significance was defined as a p-value less than 0.05. Findings: The treatment outcomes of 901 HIV-infected individuals from 9 centers in Türkiye were evaluated. After applying exclusion criteria, data from 845 individuals were included: 462 in the TDF group (mean age 43.25 ± 12.35) and 383 in the TAF group (mean age 41.75 ± 12.08) (p = 0.082). The proportion of female patients was 18.4% in the TDF group and 13.6% in the TAF group (p = 0.058). In the TDF group, 77.2% were treatment-naïve, compared to 52.2% in the TAF group (p < 0.001). At 24 months, HIV RNA levels were 14218.43 ± 233947.64 IU/ml in the TDF group and 3247.15 ± 55371.53 IU/ml in the TAF group (p < 0.001). Although CD4 levels were higher at baseline in the TAF group (p < 0.001), the TDF group showed a greater increase at 48 months (p = 0.013). ALT normalization was better in the TDF group, while total and non-HDL cholesterol levels were higher in the TAF group. Conclusion TDF and TAF-containing INSTI-based regimens exhibit distinct impacts on lipid profiles and immune function in PLWH. The early advantages of TAF in viral load reduction diminish over time, contrasting with the long-term benefits of TDF in terms of CD4 counts, ALT levels, and non-HDL cholesterol. These findings highlight the necessity of individualized treatment in selecting ART regimens.