Timing and regimen of antiretroviral therapy and all-cause mortality in people with HIV: A time-to-event mediation analysis via opportunistic infection.

Authors

Nana Wang, Ning Li, Xuezhong Shi, Xiaocan Jia, Chenyu Zhao, Yali Niu, Yongli Yang

Published in

International journal of antimicrobial agents. Pages 107904. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

To compare associations of antiretroviral therapy (ART) strategies with all-cause mortality and assess whether first opportunistic infection (OI) occurrence and time partly explain survival differences.
We analyzed 38,692 people with HIV in Henan Province (2015-2024). ART initiation timing and regimen were assessed, with early initiation defined as CD4⁺ T cell counts ≥500 cells/μL. Cox regression estimated associations with all-cause mortality and first OI. Multistate models characterized transitions to first OI and death, and time-to-event mediation analyses quantified the contribution of OI occurrence and time.
During a median follow-up of 5.07 years, 2,868 deaths occurred. Compared with late ART initiation, early initiation was associated with lower all-cause mortality (HR: 0.46; 95% CI: 0.41-0.52), and a lower transition hazard from OI to death (HR: 0.47; 95% CI: 0.27-0.81). Compared with PI-based regimens, INSTI- and NNRTI-based regimens showed lower observed all-cause mortality risks, with HRs (95% CI) of 0.51 (0.35-0.73) and 0.60 (0.50-0.72), respectively. At 5 years, early ART initiation and INSTI-based therapy were associated with absolute reductions in cumulative mortality risk of 8.51% and 4.76%, respectively, with residual disparity close to the total effect and a small shifting distribution effect (< 0.30%) attributable to first OI occurrence and time.
Earlier ART initiation, especially at CD4⁺ T cell counts ≥500 cells/μL, was associated with better survival. INSTI- and NNRTI-based regimens showed more favorable observed mortality outcomes than PI-based regimens. OI occurrence and time explained only a limited proportion of survival differences.

PMID:
42401403
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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