Keywords
AIDS diarrhea - TCM - syndrome score - adverse reaction - Meta-analysis
Introduction
Diarrhea is a common symptom of AIDS patients. It is reported that AIDS diarrhea occurs
in 60% of AIDS patients in developed countries and 90% in developing countries.[1] Different degrees of malnutrition and malabsorption may occur in patients with AIDS
diarrhea, which affects the quality of life of patients and is also one of the important
reasons for the risk of death in AIDS patients.[2] At this stage, Western medicine mostly adopts etiological and symptomatic antidiarrheal
drugs for AIDS diarrhea, such as imodium and octreotide, but the clinical treatment
effect is not ideal, and long-term use has certain adverse reactions.[3] Traditional Chinese medicine (TCM) believes that AIDS diarrhea belongs to the categories
of “diarrhea” and “dysentery.” Due to the complex pathogenesis, AIDS diarrhea is caused
mainly by spleen deficiency and dampness. Spleen disease lasts for a long time, and
it affects the kidney and forms deficiency in both spleen and kidney. Due to long-term
consumption and injury, the spleen Yang does not rise and the qi movement is disordered.
Therefore, AIDS diarrhea occurs repeatedly for a long time.[4] At present, several studies have observed TCM treatment of AIDS diarrhea patients.
Common TCM remedies include Jianpi Zhixiefang granule moxibustion, Shenling Fuzheng
Capsule, Chinese herbal packet hot compress, and Huopu Xialing decoction etc., but
lacks systematic review. This study used meta-analysis to evaluate the effect of TCM
on AIDS diarrhea patients.
Materials and Methods
Data Sources and Retrieval Methods
The articles of randomized controlled trials related to the treatment of AIDS diarrhea
by TCM were systematically searched, including database of Wanfang (WF), VIP, and
China National Knowledge Infrastructure (CNKI) as well as China Biomedical Literature
Service System, etc. The search period was set to January 1, 2010 to August 15, 2021.
The search keywords were AIDS, diarrhea, TCM, Chinese herbs, randomized controlled
experiments, etc. When searching, it is searched by subject word + free word.
Literature Inclusion and Exclusion Criteria
(1) Inclusion criteria: The research method was randomized control; the subjects included
in the experiment were patients with AIDS diarrhea; the observation indicators of
the literature included clinical efficacy, TCM symptom scores, and adverse reactions;
the patients in the included literature observation group/study group all received
TCM treatment. (2) Exclusion criteria: duplicate publications or literature with no
source data; non-randomized controlled research literature such as expert experience,
reviews, etc., no control group, or two groups without specifying treatment times;
lack of specific data for observation indicators.
Literature Screening and Quality Evaluation of Extractants
(1) Literature screening and extraction: two evaluators reviewed and assessed the
collected literature and extracted relevant data. The evaluation method was to first
read the relevant literature titles and abstracts, eliminate unqualified literature
according to the inclusion and exclusion criteria. A database was established and
the data such as the publication time of the literature, research grouping method,
and author that met the requirements were the inputs. For literature with differences,
the evaluators would reach a final conclusion after discussion. (2) Evaluation of
literature quality: The literature quality was evaluated according to the modified
Jadad scale,[5] including the four procedures of randomization, blinding, withdrawals and dropouts,
and randomized concealment.
The first three procedures were scored on a 0 to 2 scale, the last procedure uses
a 0 to 1 scale, the score ranges from 0 to 7 points, and ≥3 points are considered
high-quality articles. Among them, the first three items adopted the 0 to 2 scores,
grade 3 scoring method, and the last item adopted the 0 to 1 score, grade 1 scoring
method. The score range was 0 to 7 points, and ≥3 points were high-quality documents.
Statistical Methods
RevMan 5.0 software was used for analysis, the mean difference of 95% confidence interval
[MD (95% CI of MD)] was used to represent the measurement data, and p <0.05 was considered statistically significant. The heterogeneity between literature
was tested by I2
and p-value; p< 0.1 or I
2 >50% indicated statistical heterogeneity between literature, and the random effect
model was adopted. The inverted funnel chart was used to analyze the bias of each
published literature. If p ≥ 0.1 and I
2 ≤ 50%, there is no statistical heterogeneity between literature, and a fixed effect
model was used for analysis.
Results
Literature Screening
A total of 262 articles were selected at the preliminary stage of screening, 254 were
excluded, and eight articles were finally included, totaling 536 patients with AIDS
diarrhea. The screening flowchart is shown in [Fig. 1].
Fig. 1 Flowchart of literature screening.
Basic Characteristics of Included Literature Studies
A total of 536 patients with AIDS diarrhea were included. Among them, there were 289
cases in the observation groups/research groups and 247 cases in control groups, all
of which were domestic studies. The research characteristics of the eight included
studies are shown in [Table 1].
Table 1
Basic characteristics of included literature studies
Number
|
Included research literature
|
Research time
|
Number of patients included (cases)
|
Treatment method
|
Course of treatment
|
Observation group/Experimental group/Treatment group
|
Control group
|
Observation group/Study group
|
Control group
|
1
|
Li et al[6]
|
2016
|
19
|
18
|
Jianpi Zhixiefang Granule
|
Norfloxacin capsule, montmorillonite powder
|
2 wk
|
2
|
Li et al[7]
|
2016
|
14
|
22
|
Moxibustion
|
Saline rehydration
|
2 wk
|
3
|
Yang and Sun[8]
|
2018
|
30
|
30
|
Xielikang Capsule + basic western medicine treatment
|
Basic western medicine treatment
|
2 wk
|
4
|
Wen et al[9]
|
2016
|
33
|
32
|
Highly active anti-retroviral therapy + Shenling Fuzheng Capsule
|
Highly active anti-retroviral therapy + loperamide
|
6 wk
|
5
|
Jiao et al[10]
|
2021
|
44
|
44
|
Comprehensive western medicine + Chinese herbal packet hot compress
|
Comprehensive western medicine treatment
|
2 wk
|
6
|
Tian et al[11]
|
2012
|
94
|
46
|
Chinese herbal prescriptions of invigorating spleen to stop diarrhea
|
Imodium capsule
|
2 wk
|
7
|
Yang et al[12]
|
2013
|
41
|
41
|
Huopu Xialing Decoction + acupoint injection with water needle
|
Flufenamic Capsule
|
2 wk
|
8
|
Ren[13]
|
2013
|
14
|
14
|
Herbal prescriptions of invigorating spleen to stop diarrhea
|
Flufenamic Capsule + Smectite
|
2 wk
|
Quality Evaluation of the Included Literature
The Jadad score of 5 of the eight included articles was 2, indicating low quality.
The Jadad score of the three articles was 3, indicating the literature was of higher
quality. No literature mentioned blinding, withdrawal, and dropout ([Table 2]).
Table 2
Quality evaluation of the included literature
Included research literature
|
Sample size (cases)
|
Randomization method
|
Blinding
|
Randomized concealment
|
Withdrawal and dropout
|
Jadad score
|
Li et al
2016
|
37
|
Random number table
|
Not mentioned
|
Not mentioned
|
Not mentioned
|
3
|
Li et al
2016
|
36
|
According to the patient's wishes
|
Not mentioned
|
Not mentioned
|
Not mentioned
|
2
|
Yang and Sun
2018
|
60
|
Random number table
|
Not mentioned
|
Not mentioned
|
Not mentioned
|
2
|
Wen et al
2016
|
65
|
Random number table
|
Not mentioned
|
Not mentioned
|
Not mentioned
|
3
|
Jiao et al
2021
|
88
|
Single blinding
|
Adequate
|
Not mentioned
|
Not mentioned
|
2
|
Tian et al
2012
|
140
|
Random grouping (without indicating method)
|
Not mentioned
|
Not mentioned
|
Having dropout (without affecting results)
|
2
|
Yang et al
2013
|
82
|
Random number table
|
Not mentioned
|
Not mentioned
|
Not mentioned
|
2
|
Ren
2013
|
28
|
Double
Blinding randomization
|
Adequate
|
Not mentioned
|
Not mentioned
|
3
|
Meta-analysis of Main Outcome Measures
Clinical Efficacy
The clinical effects of TCM on AIDS diarrhea were observed in eight articles; Because
p≥ 0.1 and I2
≤50%, there was no statistical heterogeneity among the literature. The meta-analysis
of the literature was performed by using the random effect model. The results showed
that the effect of TCM on AIDS diarrhea was better, and the difference was statistically
significant [MD = 2.92, 95% CI (1.81, 4.70), p< 0.001] ([Fig. 2]).
Fig. 2 Meta-analysis forest plot of efficacy in two groups.
TCM Syndrome Scores
Four of the eight articles observed the effect of TCM on TCM syndrome scores of AIDS
patients with diarrhea, and effective data can be obtained. The included literature
was statistically consistent (I
2 = 59%, p = 0.06). The literature was meta analyzed by random effect model. The results showed
that TCM treatment of AIDS diarrhea was more conducive to improve the TCM syndrome
scores of patients [MD = −2.55, 95% CI (−3.37, −1.73), p< 0.001] ([Fig. 3]).
Fig. 3 Meta-analysis Forest plot of efficacy in two groups.
Adverse Reactions
Four of the eight articles observed the adverse reactions of AIDS diarrhea patients
treated with TCM, and effective data can be obtained. The included articles were statistically
tested (I
2≤ 50%,and p ≥0.1) and meta-analysis was performed by using random effect model. The results showed
that the adverse reactions of TCM in the treatment of AIDS diarrhea were slight, and
the difference was statistically significant [MD = 1.70, 95% CI (0.48, 5.97), p = 0.41] ([Fig. 4]).
Fig. 4 Meta-analysis forest plot of adverse reactions in two groups.
Publication Bias of Main Outcome Measures
The TCM syndrome scores of the four articles were compared and the inverted funnel
chart was compiled. SE (MD) at the vertical axis and MD at the horizontal axis. The results show that the distribution of the number and
position of each point on both sides are not symmetrical ([Fig. 5]).
Fig. 5 Meta-analysis funnel chart of TCM syndrome scores in two groups. TCM, traditional
Chinese medicine.
Discussion
Diarrhea is a common complication in AIDS patients. Long-term diarrhea will lead to
significant weight loss and seriously affect the survival treatment of patients. Therefore,
it is of great significance to make a clear effective treatment plan for AIDS diarrhea.
At present, Western medicine treatment of AIDS diarrhea varies according to the different
sources of infection; corresponding treatment drugs include antibacterial drugs, antiprotozoal,
sulfonamides, etc. They all have a certain clinical effect, but their long-term use
can develop drug resistance, which may cause intestinal flora disorder and high recurrence
rate after drug withdrawal. So, we see there are certain limitations in clinical application.[14]
TCM believes that AIDS diarrhea belongs to “diarrhea dysentery” and other categories,
and among them, spleen qi deficiency syndrome is the most common. The main pathogenesis
is spleen deficiency and serious dampness in the body, which is usually caused by
damage to the spleen and stomach caused by exogenous pathogens and endogenous dampness
inside the body.[15] There are many treatment schemes for AIDS and diarrhea mentioned in the existing
TCM research studies, including Jianpi Zhixiefang Granule, moxibustion, Shenling Fuzheng
Capsule, Chinese herbal packet hot compress, Xielikang Capsule, and Huopu Xialing
Decoction. Among them, Xielikang Capsule has the effect of killing bacteria, improving
dysentery, invigorating the spleen and tonifying the kidney, soothing intestines,
and stopping diarrhea. Jianpi Zhixie Fang is astragalus-based and is used together
in the treatment with various Chinese herbs according to different symptoms of patients,
reflecting the principle of strengthening the body resistance to eliminate pathogenic
factors, simultaneously treating both principal and subordinate symptoms.[16] Huopu Xialing Decoction was originated from Yiyuan, and it was designed for treating bodies with serious dampness and heat, which has
the effect of invigorating the spleen, removing the dampness, and stopping diarrhea.[17] The method of Chinese herbal packet hot compress originated from Shiji Wu, a doctor
in the Qing Dynasty. Applying Chinese herbal packet hot compress to Shenque (CV 8)
acupoint, Zhongwan (CV 12) acupoint, and Tianshu (ST 25) acupoint from outside to
the inside can promote the transmission of the medicine to the focus of infection
through the channel, so as to achieve the effects of regulating spleen and stomach,
strengthening the kidney and nourishing blood, stopping diarrhea and so on.[18] Moxibustion is one of the external treatment methods of TCM. Moxibustion is used
in the treatment of AIDS diarrhea patients with the method of syndrome differentiation
and acupoint, which can effectively relieve the symptoms of diarrhea, loss of appetite,
and fatigue.[19] Shenling Fuzheng Capsule is based on the Sijunzi Decoction which has the effects
of calming the heart and soothing the mind, strengthening the spleen, and nourishing
the kidney. At the same time, when taken during Sanfutian (the hottest and the most
humid day of the year), the medicine can directly treat the sickness, which not only
strengthens the body but also eliminates the “cold” caused by Yang deficiency fundamentally
improving the patient's immune system and balancing the body's Yin and Yang. This
would cause the diarrhea situation to self-recover.[20]
At present, many studies have used the above methods to treat AIDS diarrhea, but there
is a lack of systematic evaluation of relevant treatment methods. Meta-analysis is
a kind of literature quality evaluation method, which can confirm some specific research
results and evaluate the value of clinical studies by searching through relevant literature
that meets the requirements and integrates the search results.[21] This study conducted a meta-analysis on the effect of TCM on AIDS diarrhea; the
results showed that TCM was effective in the treatment of AIDS and diarrhea, and could
improve the TCM syndrome scores of patients without increasing the risk of adverse
reactions. Analysis of possible reasons: TCM treatment of AIDS and diarrhea is conducted
based on the theory of TCM syndrome differentiation, overall adjustment, focusing
on the person's body, and the combination of TCM internal and external treatment,
which can all achieve good results. It can effectively improve TCM syndrome scores,
and the adverse reactions are slight.[22] This study further analyzed the publication bias of the included literature, and
the results showed that there was a certain bias in the comparison of TCM syndrome
scores between the two groups. In view of these results, it is suggested that using
different test methods to observe the bias of the unified index in the future will
improve the credibility of the literature. In addition, only a few articles included
in this study observed the CD4+ level of patients' defecation times. Therefore, it was not taken as a key analysis
index, and future studies should focus on observing the influence of TCM on the CD4+ level of defecation times in AIDS diarrhea patients.
In conclusion, TCM in the treatment of AIDS diarrhea shows a more ideal result. It
can effectively improve the TCM syndrome scores of patients, and will not increase
the occurrence of adverse reactions.