Abstract
BACKGROUND: It is unclear whether low-level viremia (LV) during antiretroviral therapy (ART) increases the incidence of diabetes mellitus (DM). This study aims to assess the association between HIV viremia exposure during ART and DM using retrospective cohort data. METHODS: People with HIV (PWH) who started ART in 2003 or later were identified from China's National Free ART Program database. Participants who had been on ART for ≥ 6 months without DM at enrollment were included in this study. Based on two consecutive viral load measurements after 6 months of ART, participants were categorized into three groups: viral suppression (VS), transient episode low-level viremia (blips), and persistent low-level viremia (LLV). Blips and LLV were collectively classified as the LV group. We analyzed the incidence of DM depending on viremia exposure using Cox proportional hazard models adjusted for age, sex, baseline viral load, CD4 count, ART initiation regimen, ART initiation period, and WHO HIV stage. Heterogeneous linear mixed models identified fasting blood glucose (FBG) trajectory patterns during the follow-up. RESULTS: During 26,097 person-years of follow-up, we observed 1297 cases of DM in 8731 participants, with a median follow-up of 2.4 years (IQR: 1.2, 4.5). Two distinct FBG trajectories, labeled "Stable" and "Rapid increase," were identified. The LLV group had a significantly higher proportion of participants in the "Rapid increase" trajectory (OR: 2.53, p < 0.001). Both the blips (cHR: 1.40, p < 0.001) and LLV (cHR: 1.74, p < 0.001) groups were associated with a higher incidence of DM compared to the VS group. After propensity score matching, the LV group showed a higher DM risk (aHR: 1.27, p = 0.012). When restricted to the 35-49 age group, the risk of DM was even higher in both the LLV (aHR: 2.03, p = 0.017) and blips (aHR: 1.36, p = 0.027) groups compared to the VS group. CONCLUSIONS: Low-level viremia (LV) substantially increased the risk of diabetes mellitus (DM) among PWH, particularly in middle-aged individuals. Monitoring viral load and FBG is crucial to prevent DM development and improve life expectancy among ART patients.