Qiling Yiqi Tablets Plus Antiretroviral Therapy for HIV Immune Non-responders With Lung-Spleen Qi Deficiency (QLYQ-INR-pRCT)

A Pragmatic Randomized Controlled Trial of Qiling Yiqi Tablets Combined With Antiretroviral Therapy for Immune Reconstitution Failure in People With HIV and Lung-Spleen Qi Deficiency Syndrome

This pragmatic randomized controlled trial evaluates whether Qiling Yiqi Tablets combined with antiretroviral therapy (ART) improves immune reconstitution in people with HIV who meet criteria for immune reconstitution failure and lung-spleen qi deficiency syndrome. Eligible participants are adults aged 18 to 60 years with HIV-1 infection, long-term viral suppression on ART, and persistently low CD4+ T-cell counts. A total of 240 participants will be randomized 1:1 to receive Qiling Yiqi Tablets plus ART or ART alone. Treatment lasts 48 weeks, followed by 48 weeks of follow-up. The primary outcomes are absolute CD4+ T-cell count and immune reconstitution response rate. Secondary outcomes include immune homeostasis markers, T-cell activation and Treg proportion, thymic output and inflammation-related markers, HIV RNA viral load, quality of life, clinical symptom scores, all-cause mortality, and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Acquired Immunodeficiency Syndrome; HIV-1 Infection; Immune Reconstitution Failure; Immunological Non-responder; Lung-Spleen Qi Deficiency Syndrome
• Intervention / Treatment: Drug: Qiling Yiqi Tablets plus ART; Drug: Antiretroviral Therapy (ART)

Detailed Description

This is a prospective, multicenter, pragmatic, randomized, controlled clinical trial. Participants will be recruited from three HIV treatment-designated hospitals in high-prevalence regions in China. Eligible participants will be randomized by center-stratified block randomization at a 1:1 ratio to the experimental arm or control arm. Randomization codes will be generated using SAS by personnel independent from the clinical trial. The ART regimen is not restricted and follows applicable domestic and international ART guidelines. Clinical data will be collected using a unified CRF/eCRF and managed through an EDC platform with de-identified study codes and access controls.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mei Han, phD; Phone Number: +86 13401131731; Email: hanmeizoujin@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Beijing University of Traditional Chinese Medicine
      • Contact: Mei Han, phD; Phone Number: +86 13401131731; Email: hanmeizoujin@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:Aged 18 to 60 years, male or female. CD4+ T lymphocyte count <350 cells/uL. Meets diagnostic criteria for HIV-1 infection according to the Chinese Guidelines for Diagnosis and Treatment of HIV/AIDS (2024 edition).

Meets diagnostic criteria for incomplete immune reconstitution: ART for more than 4 years; peripheral blood viral load below the lower limit of detection (<50 copies/mL) for more than 3 years; persistent CD4+ T-cell count <350 cells/uL; and exclusion of other causes of long-term low CD4+ T-cell count.

Meets the Traditional Chinese Medicine diagnostic criteria for lung-spleen qi deficiency syndrome, supported by the designated four-diagnostic instrument (model SZY-ZM-1) where applicable.

Voluntarily agrees to participate and signs informed consent. -

Exclusion Criteria:Uncontrolled acute or chronic physical or mental illness. Poor adherence to ART. WBC <2 x 10^9/L, neutrophils <1.0 x 10^9/L, hemoglobin <90 g/L, platelets <75 x 10^9/L, or abnormal hepatic/renal function. Hepatic abnormality is defined as AST, ALT, or total bilirubin >=2 times the upper limit of normal; renal abnormality is defined as creatinine clearance below the normal value.

Other serious comorbid disease, such as tumor, cirrhosis, or cardiovascular/cerebrovascular disease.

Pregnancy, lactation, or recent plan for pregnancy/childbearing. Use of immunosuppressants or immunomodulators within 6 months before screening. Any other condition judged by the investigator to make the participant unsuitable for the study.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Qiling Yiqi Tablets plus ART; Participants receive Qiling Yiqi Tablets orally in addition to their background ART regimen for 48 weeks.	Drug: Qiling Yiqi Tablets plus ART; Qiling Yiqi Tablets: Qiling Yiqi Tablets are a marketed Chinese patent medicine (NMPA approval No. Z20050483; Sichuan Enwei Pharmaceutical Co., Ltd.). The formula includes Astragalus, Codonopsis, Atractylodes macrocephala, Poria, and related components. Dose: 6 tablets orally three times daily after meals with warm water for 48 weeks.Participants receive Qiling Yiqi Tablets orally in addition to their background ART regimen for 48 weeks.
Active Comparator: ART alone; Participants continue ART according to applicable domestic and international ART guidelines	Drug: Antiretroviral Therapy (ART); Background ART regimen according to applicable domestic and international ART guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute CD4+ T-cell count	Change in absolute CD4+ T-cell count, assessed by comparison between the two randomized groups.	Week 48
Immune reconstitution response rate	Response is defined as CD4+ T-cell count >350 cells/uL or a >=30% increase from baseline; non-response is defined as a <30% increase from baseline.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute CD4+ T-cell count	Change in absolute CD4+ T-cell count, assessed by comparison between the two randomized groups.	Week 96.
Immune reconstitution response rate	Response is defined as CD4+ T-cell count >350 cells/uL or a >=30% increase from baseline; non-response is defined as a <30% increase from baseline.	Week 96.
CD4+ T-cell proportion	Change in CD4+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD4+/CD8+ ratio	Change in CD4+/CD8+ ratio, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD8+ T-cell proportion	Change in CD8+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD45RA+ T-cell proportion	Change in CD45RA+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD45RO+ T-cell proportion	Change in CD45RO+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD4+CD28+ T-cell proportion	Change in CD4+CD28+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD8+CD38+ T-cell proportion	Change in CD8+CD38+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD4+CD38+ T-cell proportion	Change in CD4+CD38+ T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD38+/HLA-DR+ T-cell activation marker	Change in CD38+/HLA-DR+ T-cell activation marker, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
Treg proportion	Change in regulatory T-cell proportion, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
TRECs level	Change in T-cell receptor excision circles level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD3+ T-cell level	Change in CD3+ T-cell level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
CD31+ T-cell level	Change in CD31+ T-cell level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IL-2 level	Change in interleukin-2 level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IL-4 level	Change in interleukin-4 level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IL-6 level	Change in interleukin-6 level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IL-10 level	Change in interleukin-10 level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IL-17A level	Change in interleukin-17A level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
TNF-alpha level	Change in tumor necrosis factor-alpha level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
IFN-gamma level	Change in interferon-gamma level, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
HIV RNA viral load	Change in HIV RNA viral load, assessed by comparison between the two randomized groups.	Baseline; Weeks 48 and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
Quality of life score	Change in quality of life score assessed using the WHOQOL-HIV-BREF questionnaire, compared between the two randomized groups.	Baseline; Weeks 48, 60, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
TCM syndrome response rate	Response is defined as a >=30% decrease in TCM syndrome score from baseline; non-response is defined as a <30% decrease from baseline.	Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96.
All-cause mortality rate	Death from any cause during the study period, assessed by comparison between the two randomized groups.	From randomization through Week 96.
Red blood cell count	Change in red blood cell count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
White blood cell count	Change in white blood cell count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Hemoglobin level	Change in hemoglobin level as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Platelet count	Change in platelet count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Absolute neutrophil count	Change in absolute neutrophil count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Absolute lymphocyte count	Change in absolute lymphocyte count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Aspartate aminotransferase level	Change in aspartate aminotransferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Alanine aminotransferase level	Change in alanine aminotransferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Gamma-glutamyl transferase level	Change in gamma-glutamyl transferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Blood urea nitrogen level	Change in blood urea nitrogen level as a renal function safety laboratory indicator, assessed by comparison between the two randomized groups	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Serum creatinine level	Change in serum creatinine level as a renal function safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Urinary red blood cell result	Change in urinary red blood cell result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Urinary protein result	Change in urinary protein result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Urinary white blood cell result	Change in urinary white blood cell result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Urinary glucose result	Change in urinary glucose result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups.	Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48.
Incidence of adverse events	Incidence of adverse events during the 48-week treatment period and the post-treatment follow-up period, assessed by comparison between the two randomized groups.	Adverse events were monitored from randomization through Week 96.
Incidence of serious adverse events	Incidence of serious adverse events during the 48-week treatment period and the post-treatment follow-up period, assessed by comparison between the two randomized groups.	Serious adverse events were monitored from randomization through Week 96.
Treatment interruption rate	Proportion of participants with interruption of the assigned study treatment during the 48-week treatment period, assessed by comparison between the two randomized groups.	Treatment interruption was monitored from randomization through Week 48.
Concomitant medication use	Use of concomitant medications during the study period, including medication name, reason for use, dosage form, dose, route, frequency, start date, and end date.	Concomitant medication use was recorded from randomization through Week 96.

Collaborators and Investigators

• Sponsor: Beijing University of Chinese Medicine
• Collaborators: Chengdu University of Traditional Chinese Medicine

Publications and helpful links

General Publications

• 中华中医药学会防治艾滋病分会, 刘颖, 梁碧颜. 艾滋病中医诊疗专家共识[J]. 中国艾滋病性病, 2025, 31(9): 1029-1034. DOI: 10.13419/j.cnki.aids.2025.09.18.
• 中华医学会感染病学分会艾滋病丙型肝炎学组. 艾滋病免疫功能重建不全者临床诊疗专家共识（2023版）[J]. 中华传染病杂志, 2024, 42(1): 3-13. DOI: 10.3760/cma.j.cn311365-20230927-00098.
• 中华医学会感染病学分会艾滋病学组, 中国疾病预防控制中心. 中国艾滋病诊疗指南（2024版）[J]. 协和医学杂志, 2024, 15(6): 1261-1288. DOI: 10.12290/xhyxzz.2024-0766.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV; AIDS; Traditional Chinese Medicine; ART; CD4+ T cell; immune non-responder; incomplete immune reconstitution; Qiling Yiqi Tablets; pragmatic randomized controlled trial; pRCT
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Therapeutics; Drug Therapy; Drug Therapy, Combination; Antiretroviral Therapy, Highly Active
• Other Study ID Numbers: CTCM-HIV-INR-QLYQ-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study involves HIV-related clinical data. The clinical data will be de-identified, stored in an EDC system, and exported only after written approval by the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No