Tripterygium wilfordii Hook F accelerates CD4+ T-cell recovery in ART-treated people living with HIV with incomplete immune reconstitution: a longitudinal cohort study.

BACKGROUND: Incomplete immune reconstitution (INR) affects 9%-45% of ART-treated people living with HIV (PLWH) and is associated with increased morbidity and mortality. Chronic immune activation and inflammatory signaling, particularly via the IP-10/CXCL10 pathway, are central to its pathogenesis. Whether Tripterygium wilfordii Hook F (TwHF), an immunomodulatory agent with established anti-inflammatory properties, can improve CD4+ T-cell recovery in virologically suppressed PLWH with INR remains unclear. METHODS: We conducted a retrospective longitudinal cohort study at Peking Union Medical College Hospital. ART-treated, virologically suppressed PLWH with persistent CD4+ T-cell counts <350 cells/μL were enrolled and classified into a TwHF group (n = 32, 10 mg three times daily) or a matched control group (n = 31). Participants were followed at five predefined time points spanning 12 months pre-treatment through 12 months post-discontinuation. Peripheral blood immunophenotyping assessed CD4+ T-cell subsets (naïve and memory), CD4/CD8 ratio, and CD8+ T-cell activation markers. A cytokine substudy measured IP-10/CXCL10 and eotaxin in 20 TwHF-treated and 14 control participants using multiplex immunoassay. Linear mixed-effects models were used for longitudinal analysis. RESULTS: TwHF was associated with a significantly accelerated rate of CD4+ T-cell recovery compared with controls (group × time interaction coefficient 4.98, P < 0.001), with median counts of 254 vs. 222 cells/μL at 12 months (P = 0.011). This gain was attributable predominantly to memory CD4+ T-cell expansion (216 vs. 164 cells/μL, P < 0.001), while naïve CD4+ T-cell counts remained unchanged. The CD4/CD8 ratio improved more rapidly in the TwHF group (0.409 vs. 0.278 at month 12, P = 0.008). A clinically meaningful response (≥50 cells/μL/year) was achieved in 75.0% of TwHF-treated vs. 9.7% of controls. Within-person IP-10/CXCL10 levels declined significantly after TwHF treatment (median Δ -31.96 pg/mL, P = 0.017), particularly in good immunological responders. Immunological gains attenuated after treatment discontinuation, suggesting a treatment-dependent effect. Routine hematological and renal parameters remained within normal limits throughout follow-up, with no significant between-group differences. No serious adverse events were observed. CONCLUSION: TwHF accelerates CD4+ T-cell reconstitution in virologically suppressed PLWH with INR, primarily through memory subset expansion and modulation of IP-10/CXCL10 inflammatory signaling, supporting its potential as an adjunctive immunomodulatory strategy.