Virological effectiveness and metabolic/laboratory outcome profile of INSTI-based versus NNRTI-based initial ART in Shandong, China: a province-wide real-world cohort study

Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is increasingly used as initial treatment in China. We aimed to compare the virological effectiveness and metabolic and laboratory outcome profile of INSTI-based versus non-nucleoside reverse transcriptase inhibitor (NNRTI)-based initial ART among treatment-naïve adults with HIV in routine care. We conducted a province-wide retrospective cohort study using de-identified data from the Shandong Province subset of the National Free Antiretroviral Treatment Program database. Adults aged 18 years or older who initiated NNRTI-based or INSTI-based ART between January 1, 2023 and December 31, 2025 were included. Outcomes included documented virological suppression, documented high-level viremia between 6 and 24 months, binary metabolic and laboratory outcomes at approximately 12 months, and continuous trajectories of BMI, total cholesterol (TC), alanine aminotransferase (ALT), total bilirubin (TBIL), and creatinine-based estimated glomerular filtration rate (eGFR). Poisson regression with time offset, modified Poisson regression, Firth penalized logistic regression, and linear mixed-effects models were used as appropriate. Among 7474 ART-naïve adults, 5046 initiated NNRTI-based ART and 2428 initiated INSTI-based ART. INSTI-based initial ART was associated with a higher rate of documented virological suppression (adjusted incidence rate ratio 1.09, 95% CI 1.07–1.12) and a lower risk of documented high-level viremia (adjusted risk ratio 0.23, 95% CI 0.15–0.35). At approximately 12 months, INSTI-based ART was associated with higher risks of a ≥ 10% BMI increase, incident elevated TC, incident TBIL elevation, and ≥ 10% creatinine-based eGFR decline, but a lower risk of incident ALT elevation. Continuous trajectories showed the same direction of associations. Compared with NNRTI-based ART, INSTI-based initial ART was associated with favorable early virological outcomes alongside distinct metabolic and laboratory patterns in routine HIV care in Shandong. Given substantial differences in NRTI backbone composition, these findings should be interpreted as comparisons of contemporary treatment strategies rather than as independent effects of INSTIs. These findings support integrated post-initiation monitoring of weight, lipid levels, bilirubin, and creatinine-based renal function indicators in routine care.