Wang Yifei, Jin Fujun, Wang Qiaoli, and Suo Zucai. AIDS Research and Human Retroviruses. February 2017, 33(2): 90-92. doi:10.1089/aid.2016.0288.
Online Ahead of Print: January 31, 2017
Online Ahead of Editing: January 9, 2017
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Yifei Wang,1 Fujun Jin,1 Qiaoli Wang,1 and Zucai Suo2
1Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangdong, Guangzhou, China.
2Department
of Chemistry and Biochemistry, Public Health Preparedness for
Infectious Diseases Program, and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
ABSTRACT
Traditional
Chinese herbal medicine (TCM) has been used in Chinese society for more
than 5,000 years to treat diseases from inflammation to cancer. Here,
we report the case of nine living AIDS patients in the age range of 51
to 67 who were treated with either a unique formula of TCM alone from
2001 to 2009 or the TCM from 2001 to 2006 and then switched to
occasional antiretroviral therapy. Surprisingly, the viral loads of
eight patients were at undetectable levels on June 28, 2016, while the
remaining patient had a low viral load of 29 copies/ml. The CD4+ counts (170–592 cells/μl) and CD4+/CD8+
ratios (0.21–0.90) of the nine patients are excellent, contributing to
their current good health. Thus, the case study suggests that the TCM
has the potential to become a functional cure for HIV/AIDS.
Antiretroviral therapy (ART),
a combination of three or more small molecule inhibitors, has been
widely used to treat HIV/AIDS patients since the 1990s. Although highly
effective, ART is known to cause severe and long-term side effects to
patients. Interestingly, some of the side effects associated with ART
can be reduced by traditional Chinese herbal medicine (TCM).1 TCM also enhances patients' immune functions and reduces AIDS symptoms.1
However, there are no reports on long-term survival of AIDS patients
treated with only TCM. Here, we report a case series of nine living AIDS
patients in the age range of 51 to 67 (Table 1)
who have been infected with HIV-1 for 21 to 23 years and were treated
with either a unique formula of TCM alone or the TCM for several years
before switching to occasional ART. The TCM contains combined extracts
from 13 different plants, including Astragalus, Skullcap, and Ginseng (Experiment Methods in Supplementary Data; Supplementary Data are available online at www.liebertpub.com/aid).
Through HPLC-based fractionation and drug screening methods, others
have previously discovered that some of these plants contain
polysaccharides, protein components, alkaloids, lactones, and terpenes,
which directly inhibit the enzymatic activities of recombinant HIV-1
protease, reverse transcriptase, and integrase, as well as the
interaction between HIV-1 gp120 and immobilized CD4 receptors.1,2
The TCM also contains known natural products, which boost the immune
system, cytokine stimulation, or other pathways in patients.1,2
For example, shikonin can decrease CCR5 mRNA and the expression of
CCR5, a chemokine receptor commonly utilized by HIV to enter host
immunological cells.2
The
case series of the TCM was administered by a small Chinese company,
which bankrupted by the end of 2009. The enrolled patients, who are poor
peasants from an “AIDS Village” in Anhui Province, China, contracted
HIV-1 sometime between 1993 and 1995 through commercial plasma donation3
and were officially diagnosed at Guangzhou Center for Disease Control
and Prevention (Guangzhou, China) on December 19, 2002. At that time,
there were at least 42 HIV-infected people in the same village but few
believed that the TCM could effectively treat AIDS. Accordingly, only
nine patients were willing to participate in the case series. By late
2001, all of the nine randomly selected patients showed typical AIDS
symptoms after being infected by HIV-1 for 6 to 8 years (Supplementary Table S1), indicating that they are not “long-term nonprogressors.”4,5
For treatment, Patients A–D took the TCM twice daily from 2001 to 2009,
while Patients E–I took the TCM from 2001 or 2002 to 2006 and then
occasionally took some form of ART without TCM from 2007 to 2016 (Supplementary Table S1).
Interestingly, AIDS symptoms in all patients were improved after 3
months of the TCM treatment, and almost disappeared after 1 year of the
TCM treatment (Supplementary Table S1).
The TCM treatment was well tolerated by all patients and displayed
little clinical toxicity. While most medical data collected in the case
series were unfortunately lost due to the bankruptcy of the company,
several recovered plasma viral loads measured from 2003 to 2006 showed
significant decreases and varied from patient to patient (Table 1 and Supplementary Figs. S1 and S2). Table 1
also shows that only Patient C had a viral load of slightly lower than
2,000 copies/ml on July 24, 2003 after treatment with the TCM for 22
months. It is likely that all nine patients had much higher viral loads
than 2,000 copies/ml before they were on the TCM. This disqualifies them
from being considered as rare “viremic controllers,” who are defined as
having viral loads less than 2,000 copies/ml over time with a low
prevalence rate of 3.34% in HIV-infected patients.5
Unexpectedly, the viral loads of eight patients were at undetectable
levels as measured through COBAS AmpliPrep/TaqMan96 of Roche Molecular
Systems (detection limit: 20 copies/ml) on June 28, 2016, while Patient E
had a nearly undetectable viral load of 29 copies/ml (Table 1). Furthermore, CD4+ counts (170–592 cells/μl) and CD4+/CD8+ ratios (0.21–0.90) of the patients (Table 1 and Supplementary Fig. S3) are promising, although below the ranges for uninfected healthy adults.6,7 In comparison, a randomized clinical trial with ART on 898 US patients (ACTG 384) showed that the median CD4+
count increased from 270 cells/ml pre-ART to an estimated 532 cells/ml
seven years after starting ART in analyses ignoring treatment
discontinuations.8
Consistent with our findings, that clinical trial (ACTG 384) also
revealed that a substantial percentage of the patients starting ART at
low CD4+ counts still had low CD4+ counts after 7 years on ART.8
Taken together, the optimistic T cell parameters and, more importantly,
the extremely low viral loads presented in this case series study (Table 1)
collectively contribute to the present good health of all patients who
are currently carrying out arduous agricultural work. Strikingly,
Patients A–D, who have never taken ART and were on the TCM from 2001 to
2009 have not been on any medical treatment since 2010 (Supplementary Table S1),
yet, survived more than 15 years after AIDS onset. In contrast, without
medical treatment, 82% of 294,662 patients in a published meta-analysis
progressed from AIDS onset to AIDS-related deaths within 6 years.6
Consistently, more than 30 HIV-infected patients in the same “AIDS
Village” as Patients A–D died from AIDS between 1999 and 2003. Notably,
none of these deceased patients took the TCM or any form of ART, which
were inaccessible to poor Chinese peasants at that time.However, unlike randomized controlled clinical trials, there was not a control patient group who took a proper placebo during this case series. In addition, the case series has a small sample size and eight of the nine enrolled patients are married couples. The TCM was neither randomly administered nor quantitatively monitored.
The case
series data presented here, although incomplete and uncontrolled,
demonstrate the promise of the TCM. Therefore, the TCM merits further
and more rigorous evaluation through biochemical and biological studies,
animal model testing, and randomized controlled clinical trials.1
It would also be important to monitor the ART levels in the control
group and patient cohorts to verify patient compliance of therapeutic
regimens during future clinical investigation. If validated through
these rigorous tests, the TCM can be utilized as a cost-effective
HIV/AIDS treatment alone or in combination with ART, potentially
contributing to a strategy for functional cure.
Acknowledgments
This
work was supported by the National Natural Science Foundation of China
(grants 81274170 and 81573471) and the International Cooperation Project
of Guangdong Province (grant 2015A050502028) to Y.W., and the
discretionary fund from The Ohio State University to Z.S.
Authors' Contributions
Y.W.
and Z.S. designed the project. Y.W. and Q.W. collected the data. Y.W.,
F.J., and Z.S. analyzed the data. Z.S. wrote the manuscript. Z.S., F.J.,
and Y.W. edited the manuscript.
Ethics Committee Approval
The authors received approval from the Ethics Committee at Jinan University.
Author Disclosure Statement
No competing financial interests exist.
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