A population-based retrospective cohort study conducted at China Medical University Hospital in Taichung, Taiwan, has revealed that Chinese herbal medicine significantly reduces all-cause mortality in HIV/AIDS patients with neurological diseases. The study, published in Frontiers in Pharmacology, evaluated 1,209 patients diagnosed with both HIV/AIDS and neurological disorders between 2010 and 2017, identifying a 70% reduction in all-cause mortality for Chinese herbal medicine users compared with matched non-users. The adjusted hazard ratio (aHR) was 0.30 with a 95% confidence interval (CI) of 0.16 to 0.58 (p < 0.001) [1].
The study used Taiwan’s National Health Insurance Research Database (NHIRD) and included 20,355 HIV/AIDS patients initially screened for eligibility. Patients with neurological complications were included if they had at least one inpatient or three outpatient visits for diagnoses categorized as central nervous system infections, cognitive disorders, vasculopathies, or peripheral neuropathies. After exclusions for pre-existing neurological diseases, malignancy, or insufficient Chinese herbal medicine exposure (fewer than 14 cumulative days within the first year of neurological diagnosis), 308 Chinese herbal medicine users and 901 non-users remained. Propensity score matching (1:2 ratio) based on age, sex, Charlson comorbidity index (CCI), and duration between HIV/AIDS and neurological disease diagnosis resulted in 266 Chinese herbal medicine users and 532 matched non-users for final analysis [1].
Herbal Formulas and Single Herbs
Among Chinese herbal medicine users, a total of 7,376 prescriptions were recorded. The most frequently prescribed formulas included:
- Long Dan Xie Gan Tang: 459 prescriptions
- Ban Xia Xie Xin Tang: 407 prescriptions
- Ge Gen Tang: 390 prescriptions
- Suan Zao Ren Tang: 280 prescriptions
The most frequently used single herbs were:
- Huang Qin (Scutellaria baicalensis): 557 prescriptions
- Gan Cao (Glycyrrhiza uralensis): 540 prescriptions
- Da Huang (Rheum palmatum): 528 prescriptions
- Jie Geng (Platycodon grandiflorus): 466 prescriptions
Two key Chinese herbal medicine prescription clusters emerged from association rule mining and network analysis. Cluster one comprised Huang Qin, Gan Cao, Jie Geng, Huang Lian (Coptis chinensis), and Huang Bai (Phellodendron amurense). Cluster two included Suan Zao Ren Tang and Ye Jiao Teng (Polygonum multiflorum). These clusters were identified based on prescription frequency, support, confidence, and lift metrics [1].
Mortality and Risk Reductions
The cumulative incidence of all-cause mortality was significantly lower among Chinese herbal medicine users, as illustrated by Kaplan–Meier survival curves (log-rank test, p = 0.0007). Adjusted Cox proportional hazards modeling showed that Chinese herbal medicine users had a 70% lower risk of all-cause mortality (aHR: 0.30; 95% CI: 0.16–0.58; p < 0.001). Risk reduction remained significant even after adjusting for comorbidities, ART drug exposure, sex, and age. Infections, parasite-related, and circulatory mortality were also reduced by 86% in the Chinese herbal medicine group (aHR: 0.14; 95% CI: 0.04–0.46; p = 0.001) [1].
ART regimens refer to antiretroviral therapy regimens, which are standardized combinations of medications used to treat HIV infection. These regimens typically include a combination of three or more antiretroviral drugs from at least two different classes, such as:
- NRTIs (nucleoside reverse transcriptase inhibitors)
- NNRTIs (non-nucleoside reverse transcriptase inhibitors)
- PIs (protease inhibitors)
- INSTIs (integrase strand transfer inhibitors)
The goal of ART is to suppress HIV viral replication, restore and preserve immune function, reduce HIV-related morbidity and mortality, and prevent transmission. ART is a global standard of care for people living with HIV.
Mechanistic and Clinical Insights
While laboratory biomarkers were not available due to limitations in the NHIRD, the therapeutic rationale was supported by pharmacological knowledge of the herbal constituents. For example:
- Huang Qin contains baicalein, a flavone with antioxidant, anti-inflammatory, and neuroprotective properties.
- Gan Cao has glycyrrhizin, known for immunomodulatory and hepatoprotective effects.
- Jie Geng contains platycodin D, linked to improved cognitive function.
- Huang Bai and Huang Lian are traditional heat-clearing herbs with antimicrobial and anti-inflammatory actions.
- Suan Zao Ren Tang and Ye Jiao Teng have been used for sleep, anxiety, and mood disorders, indicating benefits for neurocognitive support [1].
The most common formula, Long Dan Xie Gan Tang, includes herbs like Long Dan Cao (Gentiana scabra), Zhi Zi (Gardenia jasminoides), and Chai Hu (Bupleurum chinense), which collectively support liver function and clear damp-heat, potentially addressing systemic inflammation and hepatic stress related to ART toxicity or HIV progression [1].
Strength and Limitations
The study employed rigorous statistical techniques including Kaplan-Meier survival analysis, multivariate Cox regression, and sensitivity analyses limited to specific subgroups such as patients with central nervous system infections. Even in this subgroup, Chinese herbal medicine use remained protective (aHR: 0.10; 95% CI: 0.03–0.39; p < 0.001) [1].
Limitations included lack of biomarker data (e.g., cytokines, viral load), lifestyle factors, and treatment adherence metrics. Despite this, the study provides strong population-level evidence that Chinese herbal medicine, when administered under licensed practitioners and integrated with ART, can confer a survival benefit for HIV/AIDS patients with neurological disease.
Conclusion
This study presents robust observational data supporting the adjunctive use of Chinese herbal medicine in reducing mortality among HIV/AIDS patients with neurological complications. Prescriptions such as Long Dan Xie Gan Tang, Ban Xia Xie Xin Tang, Ge Gen Tang, and Suan Zao Ren Tang, as well as single herbs like Huang Qin, Gan Cao, Jie Geng, and Huang Bai, are associated with improved survival outcomes. These findings suggest that Chinese herbal medicine may provide immunological and neuroprotective benefits that complement standard ART regimens. Further randomized controlled trials are warranted to confirm causality and establish protocolized Chinese herbal medicine treatment pathways for neuro-AIDS care.
Source:
1. Chiou, Jian-Shiun, et al. "Effect of Chinese Herbal Medicine Therapy on Risks of All-Cause Mortality, Infections, Parasites, and Circulatory-Related Mortality in HIV/AIDS Patients with Neurological Diseases." Frontiers in Pharmacology 14 (2023).
