Introduction: The incidence rate of newly diagnosed HIV infection in Indonesia decreased from 21 per 100,000 in 2011 to 10 per 100,000 in 2021. Despite this progress, AIDS-related deaths among people living with HIV (PLWH) increased from 3.4% in 2010 to 4.8% in 2020. Determining risk factors for mortality may identify areas to intervene and reduce mortality. Methods: A multicenter, prospective, observational cohort study of HIV infection, coinfections, and comorbidities (INA-PROACTIVE) was carried out at 19 hospitals across major islands in Indonesia. The study enrolled PLWH from 2018–2020 and followed them for 3 years. For this analysis, PLWH ≥ 18 years old with one year of follow-up data were included. Cox regression was used to identify variables at enrollment that correlated with one-year mortality. Results: Among the 4,050 PLWH analysed in the study, 68.8% were male, 53.5% acquired HIV through heterosexual transmission, 92.4% were on antiretroviral treatment (ART) at enrollment, and 72.4% had an undetectable viral load. At one year, 115 (2.8%) had died. Detectable viremia at enrollment was significantly associated with mortality, with the risk increasing as the viral load (VL) category increased (adjusted hazard ratio [aHR] 4.47, 95% CI: 1.47–13.56 for VL 50 to < 1,000 copies/mL; aHR 7.88, 95% CI: 2.80–22.20 for VL 1,000 to 10,000 copies/mL; and aHR 18.33, 95% CI: 7.94–42.34 for VL > 10,000 copies/mL; compared to VL < 50 copies/mL). Other factors at enrollment significantly associated with mortality were a CD4 + count < 200 (aHR 8.02, 95% CI: 2.69–23.86; compared to ≥ 350), age 40–49 years (aHR 2.19, 95% CI 1.23–3.87; compared to 18–29 years) and being underweight (aHR 1.84, 95% CI: 1.18–2.85; compared to normal weight). Conclusions: Among predominantly treatment-experienced PLWH, detectable viremia and continued immunosuppression were significantly associated with one-year mortality. This study highlights the importance of ART with complete viral suppression as well as immune recovery to prevent mortality. Trial registration: Clinical Trial Number: NCT03663920, registration date: 4 January 2018. © The Author(s) 2025.