Acquired Immunodeficiency Syndrome, HIV-1 Infection, Immune Reconstitution Failure, Immunological Non-responder, Spleen-Kidney Yang Deficiency Syndrome
Conditions
Keywords
HIV, AIDS, immune non-responder, incomplete immune reconstitution, ART, CD4+ T cell, Traditional Chinese Medicine, Fuyang Jiedu Granules, pragmatic randomized controlled trial, pRCT
Brief summary
This pragmatic randomized controlled trial evaluates whether Fuyang Jiedu Granules combined with antiretroviral therapy (ART) improves immune reconstitution in people with HIV who meet criteria for immune reconstitution failure and spleen-kidney yang 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 Fuyang Jiedu Granules 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.
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.
Interventions
DRUGFuyang Jiedu Granules
Fuyang Jiedu Granules are provided by Quantaitang Group Co., Ltd. (Chinese invention patent No. ZL201210251214.7). The main components include Polygonatum, Epimedium, deer antler, Codonopsis, Scutellaria baicalensis, Scutellaria barbata, and related components. Dose: 1 sachet (9 g) orally twice daily, 30 minutes after morning and evening meals, with warm water for 48 weeks.
Background ART regimen according to applicable domestic and international ART guidelines.
Sponsors
Beijing University of Chinese Medicine
Beijing YouAn Hospital
Capital Medical University
Chengdu Public Health Clinical Center
Chongqing Public Health Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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 spleen-kidney yang 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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute CD4+ T-cell count | Week 48. | Change in absolute CD4+ T-cell count, assessed by comparison between the two randomized groups. |
| Immune reconstitution response rate | Week 48. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute CD4+ T-cell count | Week 96 | Change in absolute CD4+ T-cell count, assessed by comparison between the two randomized groups. |
| Immune reconstitution response rate | Week 96 | 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. |
| CD4+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD4+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD4+/CD8+ ratio | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD4+/CD8+ ratio, assessed by comparison between the two randomized groups. |
| CD8+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD8+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD45RA+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period aUrinary red blood cell resultnd follow-up assessments were Weeks 48 and 96. | Change in CD45RA+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD45RO+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD45RO+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD4+CD28+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD4+CD28+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD8+CD38+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD8+CD38+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD4+CD38+ T-cell proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD4+CD38+ T-cell proportion, assessed by comparison between the two randomized groups. |
| CD38+/HLA-DR+ T-cell activation marker | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD38+/HLA-DR+ T-cell activation marker, assessed by comparison between the two randomized groups. |
| Treg proportion | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in regulatory T-cell proportion, assessed by comparison between the two randomized groups. |
| TRECs level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in T-cell receptor excision circles level, assessed by comparison between the two randomized groups. |
| CD3+ T-cell level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD3+ T-cell level, assessed by comparison between the two randomized groups. |
| CD31+ T-cell level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in CD31+ T-cell level, assessed by comparison between the two randomized groups. |
| IL-2 level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interleukin-2 level, assessed by comparison between the two randomized groups. |
| IL-4 level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interleukin-4 level, assessed by comparison between the two randomized groups. |
| IL-6 level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interleukin-6 level, assessed by comparison between the two randomized groups. |
| IL-10 level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interleukin-10 level, assessed by comparison between the two randomized groups. |
| IL-17A level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interleukin-17A level, assessed by comparison between the two randomized groups. |
| TNF-alpha level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in tumor necrosis factor-alpha level, assessed by comparison between the two randomized groups. |
| IFN-gamma level | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in interferon-gamma level, assessed by comparison between the two randomized groups. |
| HIV RNA viral load | Baseline; Weeks 48 and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in HIV RNA viral load, assessed by comparison between the two randomized groups. |
| Quality of life score | Baseline; Weeks 48, 60, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Change in quality of life score assessed using the WHOQOL-HIV-BREF questionnaire, compared between the two randomized groups. |
| TCM syndrome response rate | Baseline; Weeks 12, 24, 36, 48, 60, 78, and 96 were observed. The treatment-period and follow-up assessments were Weeks 48 and 96. | Response is defined as a \>=30% decrease in TCM syndrome score from baseline; non-response is defined as a \<30% decrease from baseline. |
| All-cause mortality rate | From randomization through Week 96. | Death from any cause during the study period, assessed by comparison between the two randomized groups. |
| Red blood cell count | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in red blood cell count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| White blood cell count | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in white blood cell count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Hemoglobin level | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in hemoglobin level as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Platelet count | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in platelet count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Absolute neutrophil count | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in absolute neutrophil count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Absolute lymphocyte count | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in absolute lymphocyte count as a blood routine safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Aspartate aminotransferase level | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in aspartate aminotransferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Alanine aminotransferase level | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in alanine aminotransferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Serum creatinine level | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in serum creatinine level as a renal function safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Urinary red blood cell result | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in urinary red blood cell result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Gamma-glutamyl transferase level | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in gamma-glutamyl transferase level as a liver function safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Urinary protein result | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in urinary protein result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Urinary white blood cell result | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in urinary white blood cell result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Urinary glucose result | Baseline; Weeks 12, 24, and 48 were observed. The safety laboratory assessments were Weeks 12, 24, and 48. | Change in urinary glucose result as a urinalysis safety laboratory indicator, assessed by comparison between the two randomized groups. |
| Incidence of adverse events | Adverse events were monitored from randomization through Week 96. | 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. |
| Incidence of serious adverse events | Serious adverse events were monitored from randomization through Week 96. | 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. |
| Treatment interruption rate | Treatment interruption was monitored from randomization through Week 48. | Proportion of participants with interruption of the assigned study treatment during the 48-week treatment period, assessed by comparison between the two randomized groups. |
| Concomitant medication use | Concomitant medication use was recorded from randomization through Week 96. | Use of concomitant medications during the study period, including medication name, reason for use, dosage form, dose, route, frequency, start date, and end date. |
Countries
China
Contacts
CONTACTMei Han, phD
Outcome results
None listed