A combined eGFR-CD4 index and mortality risk among people with HIV: a retrospective cohort study in Taizhou city, Zhejiang province, China

AIDS Research and Therapy https://doi.org/10.1186/s12981-026-00894-1 Article in Press A combined eGFR-CD4 index and mortality risk among people with HIV: a retrospective cohort study in Taizhou city, Zhejiang province, China Congcong Guo, Xinxin Xing, Qiguo Meng, Shanling Wang, Yali Xie, Tailin Chen, Jiyuan Ren, Xiaoxiao Chen & Haijiang Lin Received: 23 March 2026 Accepted: 30 April 2026 Cite this article as: Guo C., Xing X., Meng Q. et al. A combined eGFR-CD4 index and mortality risk among people with HIV: a retrospective cohort study in Taizhou city, Zhejiang province, China. AIDS Res Ther (2026). https://doi. org/10.1186/s12981-026-00894-1 A S S We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ACCEPTED ARTICLEMANUSCRIPT IN PRESS A Combined eGFR-CD4 Index and Mortality Risk Among People With HIV: A Retrospective Cohort Study in Taizhou City, Zhejiang Province, China Congcong Guo1,*, Xinxin Xing2,*, Qiguo Meng2, Shanling Wang2, Yali Xie2, Tailin Chen3, Jiyuan Ren3, Xiaoxiao Chen3,4,#, Haijiang Lin2,3,# 1 Jiaojiang Center for Disease Control and Prevention (Jiaojiang S S E Institute of Health Supervision), Taizhou, Zhejiang, 318000, China 2 PR Taizhou Center for Disease Control and Prevention (Taizhou IN Institute of Health Supervision), Taizhou, Zhejiang, 318000, China E L C 3 Department of Epidemiology, School of Public Health, Fudan I T AR University, Shanghai 200032, China 4 Taizhou Central Blood Station, Taizhou, Zhejiang, 318000, China * Congcong Guo and Xinxin Xing contributed equally to this article. # Corresponding authors: Xiaoxiao Chen, Email:; Lin Haijiang, Email: ACCEPTED ARTICLEMANUSCRIPT IN PRESS Abstract Background Mortality among people with HIV (PWH) increasingly reflects both HIV-related and non-HIV-related causes. Whether a simple index integrating routinely measured kidney and immune function can S S E improve risk stratification remains uncertain. Methods E L C PR IN We conducted a retrospective cohort study in Taizhou, Zhejiang, China using Information I T AR the China Management HIV/AIDS System Comprehensive linked to a Response cause-of-death surveillance system. Adults aged ≥18 years diagnosed with HIV between 1998 and 2024 who had at least one paired serum creatinine and CD4 measurement were followed through 31 December 2024. Time-updated estimated glomerular filtration rate (eGFR), CD4, and a combined eGFR-CD4 index (CBI) were analysed using time-dependent Cox models. Restricted cubic splines assessed non-linearity, and 12-month landmark analyses with ACCEPTED ARTICLEMANUSCRIPT IN PRESS time-dependent receiver operating characteristic curves evaluated discrimination. Bootstrap internal validation was performed. Results Among 3683 PWH (median follow-up 5.61 years), 434 deaths occurred, including 67 HIV-related and 367 non-HIV-related deaths. Each 1-SD increase in CBI was associated with higher risks of all-cause, HIV-related, and non-HIV-related mortality, with adjusted hazard ratios of 4.12 (95% CI: 2.76-6.15), 37.86 (95% CI: S S E 9.03-158.80), and 3.30 (95% CI: 2.20-4.93), respectively (all P < PR 0.001). Landmark analyses showed graded risk separation across IN CBI quartiles. After bootstrap internal validation, the combined E L C model showed modestly higher discrimination for all-cause and I T AR non-HIV-related mortality, whereas CD4 alone performed best for HIV-related mortality. Conclusions A time-varying combined eGFR-CD4 index was associated with mortality outcomes in this cohort of PWH in Taizhou, Zhejiang, China. Its discriminatory advantage after internal validation was modest and was evident for all-cause and non-HIV-related, but not HIV-related, mortality. External validation is warranted. ACCEPTED ARTICLEMANUSCRIPT IN PRESS Keywords HIV; mortality; CD4; estimated glomerular filtration rate; risk stratification S S E Background E L C IN PR People with HIV (PWH) are living longer in the antiretroviral I T AR therapy (ART) era, yet mortality remains substantial and increasingly reflects a mix of HIV-related and non-HIV-related causes. In 2024, an estimated 40.8 million (37.0-45.6 million) people were living with HIV worldwide, and (490,000-820,000) died from HIV-related causes[1, 2]. 630,000 As ART coverage expands and populations age, the proportion of deaths attributable to non-AIDS-related conditions has increased in many settings[3, 4]. changing cause-of-death In China, national surveillance likewise suggests patterns alongside the scale-up of ACCEPTED ARTICLEMANUSCRIPT IN PRESS universal ART policies[5]. Two routinely collected clinical markers capture key biological domains central to long-term prognosis in PWH: kidney function and immune status. Reduced estimated glomerular filtration rate (eGFR) reflects kidney impairment and cumulative comorbidity burden and has been associated with higher mortality risk in diverse HIV cohorts[6-9]. CD4 cell count remains a cornerstone marker of immune function; longitudinal studies demonstrate a S S E strong gradient between time-updated CD4 levels and subsequent PR risk of AIDS events and death, with evidence that risk reductions IN may plateau at higher CD4 ranges[10, 11]. E L C I T AR Multivariable risk scores, such as the Veterans Aging Cohort Study (VACS) Index 2.0, integrate HIV-related and general biomarkers and show good discrimination for mortality[12]. However, their complexity may limit routine implementation, and they are not designed to directly address HIV-related vs non-HIV-related mortality in settings where causes of death are shifting. Whether contemporaneous renal and immune function jointly contribute to prognosis when (...truncated)