| Research Article |
Open Access |
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| Impact of Adjunct Immunotherapy with Multi-herbal
Supplement Dzherelo (Immunoxel) on Treatment
Outcomes in End-stage TB/HIV Patients |
| Olga V. Arjanova1, Nathalia D. Prihoda1, Larisa V. Yurchenko1, Nina I. Sokolenko1, Lyudmila A. Vihrova2, Volodymyr S. Pylypchuk3, Valery M. Frolov4, Galyna A. Kutsyna4* |
| 1Lisichansk Tuberculosis Dispensary, Lisichansk, Ukraine |
| 2Lisichansk Regional Hospital, Lisichansk, Ukraine |
| 3Ekomed LLC, Kiev, Ukraine |
| 4Luhansk Regional AIDS Center and Luhansk State Medical University, Luhansk, Ukraine |
| *Corresponding author: |
Dr. Galyna A. Kutsyna MD,
PhD, Luhansk State
Medical University,
50-years of Defense of Luhansk street Luhansk
91045, Ukraine,
Tel : +380508093822,
Fax: +3806454347106,
E-mail : kutsyna@list.ru |
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| Received September 12, 2009; Accepted December 30, 2009; Published December 30, 2009 |
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| Citation: Arjanova OV, Prihoda ND, Yurchenko LV, Sokolenko NI, Vihrova LA, et al. (2009) Impact of Adjunct Immunotherapy with Multi-herbal Supplement Dzherelo (Immunoxel) on Treatment Outcomes in End-stage TB/HIV Patients. J Antivir Antiretrovir 1: 086-088. doi:10.4172/jaa.1000013 |
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| Copyright: © 2009 Arjanova OV et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited. |
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| Abstract |
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| Prognosis for TB/HIV co-infection is very unfavourable.
In terminally-ill patients treatment options are often limited
to palliative care. In our salvage, 2-month therapy of
40 late-stage TB/HIV patients we administered to half of
the patients TB drugs along with over-the-counter botanical
immunomodulator Dzherelo (Immunoxel). Despite best
possible care 6 patients had died. Remaining 14 patients
experienced marked clinical improvements and one patient
was discharged due to full recovery. Among 20
matched subjects on conventional TB regimen, 12 died
and only one was slightly better-off. These results indicate
that Dzherelo might reduce mortality (P=0.055) and
improve significantly the quality of life (P=0.00002). Improvement
in quality of life is also supported by substantial
weight gain (mean/median 3.3/4 kg) in much higher
proportion of patients than among those who received TB
drugs only, i.e., 16 vs. 1 (P=0.000001). At the end of two
months 13 (65%) patients became sputum smear negative
versus only one individual (5%) in ATT group
(P=0.00007). These results suggest that adjuvant immunotherapy
improves significantly therapy outcome and
reduces mortality. Larger study is warranted to confirm
the benefit of Dzherelo. |
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| Keywords |
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| AIDS; End-stage; Herbal; Mycobacterium; Mortality;
Quality of life; Salvage therapy; Survival; Terminal disease |
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| Introduction |
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| HIV-positive individuals with tuberculosis are particularly vulnerable
since standard anti-TB (ATT) and anti-HIV drugs (ART)
are not very effective in this category of patients and prognosis
is worse than for two infections separately (Kang’ombe et al.,
2004). In the terminal stage of TB/HIV treatment options are
severely restricted and it is usually too late to seek any meaningful
therapy. Patients with TB/HIV are often from the low social
strata and cannot afford expensive antiretroviral therapy, which
could potentially prolong their life. Ukrainian health authorities
do provide free TB drugs, but supplies of ART are limited and
terminal TB/HIV patients are not on the priority list and thus
seldom have a chance to receive them. Due to these unfortunate
circumstances most patients are left without ART option. These
patients are often ostracized, denied medical care at specialized
AIDS clinics due to fear of airborne spread of tuberculosis, and
usually end up in TB dispensaries where their only treatment option is antibiotics. At this stage the quality of life is very poor
and mortality is high. |
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| Dzherelo is a multi-herbal oral immunomodulator, recommended
but not approved by the health authorities of Ukraine as
an adjunct therapy for TB (Chechitiany et al., 2007). We and others
have conducted several clinical trials involving TB/HIV-positive
volunteers, which have shown that when Dzherelo and ATT
are combined the quality of life and TB cure rates are drastically
improved (Chechitiany et al., 2007; Prihoda et al., 2007; Nikolaeva et al., 2008; Nikolaeva et al., 2008; Prihoda et al.,
2008). Adjunct immunotherapy has been shown to achieve faster
and higher score of mycobacterial clearance, reduce HIV burden,
accelerate healing of pulmonary lesions, decrease inflammation
and liver damage, improve hematology picture, e.g.,
higher hemoglobin levels and CD4 counts, and enhance significantly
quality of life (QOL) such as weight gain, fever, respiratory
function, physical fitness, emotional well-being and better
mood. In end-stage stage disease, however, the death is a critical
endpoint, which defines unequivocally the merit of therapeutic
intervention. In this study we investigated whether in addition to
previously demonstrated positive clinical and QOL outcomes
Dzherelo can reduce mortality rate. |
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| Materials and Methods |
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| Patient population and intervention |
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| This project started as a salvage therapy for patients with extremely
poor prognosis (Prihoda et al., 2008). At any given time
our TB dispensary has 80-100 end-stage hospitalized TB patients
of which about 2/3 are HIV infected. The turnover is quite
fast - an average upper life expectancy is about 5-6 months. Since
dramatic differences were observed when we used Dzherelo in
non-terminal TB and HIV cases, we thought that terminally-ill
patients may also benefit from this intervention. We thus gave Dzherelo to those without any reasonable prospect of survival,
but surprisingly the outcome was startling and much better than
we initially anticipated. Such results were clearly unprecedented
but a control was needed to advance our findings beyond anecdotal
level. After long deliberation our Ethics board had decided
that our salvage therapy can evolve into a clinical trial with matching
arms provided that patients in ATT alone arm gave their informed
consent. For us, it was and still is a difficult ethical issue
as to which patient will receive potentially life-saving intervention
and which one will not. In May 2008 the MAPI Trust graciously
gave us a small contribution, which we used to start this
project. Twenty end-stage TB/HIV patients received individualized
TB drugs regimen while matching control group of patients
had same TB drugs supplemented with 50 drops of Dzherelo
given in a half-a-glass of water twice-a-day. |
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| Follow-up procedures and statistics |
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| At study entry all patients with confirmed HIV-positive test
had a physical examination, chest X-ray, and sputum analysis
for the presence of Mycobacterium tuberculosis. Patients were
given best palliative care and followed on a daily basis. Those
who remained alive were analyzed again two months later. The
statistical difference between two groups was measured by
Fisher’s exact 2x2 test with P threshold value set at =0.05. |
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| Results |
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| Forty terminally-ill TB/HIV volunteers entered into this comparative
study. At the end of 2 months of follow-up 6 patients in
Dzherelo group had died despite best possible palliative care
(Table 1). In remaining 14 patients marked clinical improvement
was observed and one patient was discharged due to full
recovery from TB symptoms. By comparison, among 20 terminally-
ill, matched group of patients receiving conventional TB
drugs, 12 patients died and only one person had experienced a
limited clinical improvement. These results indicate that when
Dzherelo is co-administered with chemotherapy to end-stage TB/
HIV patients it might reduce mortality (P=0.055) and improve
significantly the quality of life (P=0.00002). Improvement in
quality of life among Dzherelo recipients is also supported by
substantial weight gain (mean/median 3.3/4 kg; range 1-7 kg) in
much higher proportion of patients than among those who received
TB drugs only, i.e., 16 vs. 1 (P=0.000001). Positive
changes as evidenced by sputum smear clearance and radiological
improvements were equally impressive. At the end of two
months 13 (65%) patients became sputum smear negative versus
only one individual (5%) in ATT group (P=0.00007). In opinion
of the treating physician one patient in Dzherelo group had
fully recovered and was hence discharged from the dispensary.
However this was a single case and statistically not significant
(P=0.5) even though none of the patients on TB drugs alone had
recovered to that extent. |
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| Table 1: Preliminary findings in 40 end-stage TB/HIV patients treated for 2 months. |
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| Discussion |
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| In developing countries TB is the primary cause of AIDS-related
deaths and it is agreed that available treatment options are
not satisfactory (Kang’ombe et al., 2004; Cain et al., 2007; Ngo
et al., 2007; Swaminathan et al., 2008; Saraceni et al., 2008).
Our preliminary findings in 40 terminally-ill TB/HIV patients
indicate that botanical immunomodulator Dzherelo can significantly
improve the quality of life and reduce mortality. However,
the probability value of better survival compared to conventional
TB therapy was marginally significant (P=0.055) indicating
that larger population is needed to verify our preliminary
observation. To the best of our knowledge there is only one
study, which reported positive effect of immunotherapeutic ntervention
on survival of terminally-ill AIDS patients
(Metadilogkul et al., 2005). In that study approximately one
hundred patients were enrolled to show the significance implying
that we may need a similar size population. |
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| Quality of life parameters as judged by weight gain and
physician’s assessed clinical improvement were highly significant,
P=0.000001 and P=0.0002, respectively. We need, however,
develop better methods so that patient reported outcomes
(PRO) can be assessed more objectively either by adopting existing
questionnaires such as SF-36 or WHOQOL-100. Ideally,
we would need to measure outcomes that could assess both HIV
and TB associated symptoms – instruments for these two conditions,
MOS-HIV and TBscore, were developed by Wu et al.,
and Wejse et al., respectively (Grossman et al., 2003; Wejse et
al., 2008). Such tools will help us to have better understanding
of QOL parameters in dually infected patients and will certainly
add more substance to our study. |
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| We do have government-supplied free TB drugs for all patients
but at terminal stage they are not very effective and many
patients default treatment due to adverse effects and lack of
progress. Dzherelo is not very expensive but our resources are
limited to afford covering every terminally-ill patient. During
other clinical trials in non-terminal categories of TB patients we
had free supplies of Dzherelo from the manufacturer – Ekomed
LLC (Chechitiany et al., 2007; Prihoda et al., 2007; Nikolaeva
et al., 2008; Nikolaeva et al., 2008; Prihoda et al., 2008). Even
though Ekomed has been quite generous it is difficult to expect
that a commercial company will be willing to support all endstage
patients hospitalized in the dispensary. |
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| There is an urgent need to expand treatment options for terminally-
ill TB patients with or without HIV (Cain et al., 2007; Ngo
et al., 2007; Swaminathan et al., 2008; Saraceni et al., 2008; Metadilogkul et al., 2005). Our preliminary findings are encouraging
but we need to carry out larger study to confirm them.
This may allow us to persuade the public opinion and health
authorities that an herbal supplement is worth being considered as an integral part of centralized free TB drugs supplies. As a
result lives of many thousands TB patients may be saved in
Ukraine and elsewhere. Our dream of helping terminally-ill
people to improve quality of life and commute their death sentence
will be then materialized. |
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| Acknowledgements |
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| This study was supported by compassionate financial support
graciously provided by MAPI Research Trust, Lyon, France - a
non-profit organization that advances the art and the use of scientific
approaches to patient-reported outcome measures. |
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| References |
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- Cain KP, Kanara N, Laserson KF, Vannarith C, Sameourn K, et al. (2007)
The epidemiology of HIV-associated tuberculosis in rural Cambodia. Int J
Tuberc Lung Dis 11: 1008-13. » CrossRef » PubMed » Google Scholar
- Chechitiany R, Pylypchuk V, Arjanova O, Prihoda N, Vihrova L, et al. (2007)
Comparative effect of an immunomodulator Immunoxel (Dzherelo) when
used alone or in combination with antiretroviral therapy in drug-naïve HIV
infected individuals. Intl J Biotechnol 9: 267-276. » Google Scholar
- Grossman HA, Sullivan PS, Wu AW (2003) Quality of life and HIV: current
assessment tools and future directions for clinical practice. AIDS Read 13:
583-90, 595-7. » CrossRef » PubMed » Google Scholar
- Kang’ombe CT, Harries AD, Ito K, Clark T, Nyirenda TE, et al. (2004)
Long-term outcome in patients registered with tuberculosis in Zomba,
Malawi: mortality at 7 years according to initial HIV status and type of TB.
Int J Tuberc Lung Dis 8: 829-36. » CrossRef » PubMed » Google Scholar
- Metadilogkul O, Jirathitikal V, Bourinbaiar AS (2005) Prolonged survival
of end-stage AIDS patients immunized with therapeutic HIV vaccine V-1
Immunitor. Biomed Pharmacother 59: 469-73. » CrossRef » PubMed » Google Scholar
- Ngo AT, Duc NH, Lan NH, Maynart M, Mayaud C, et al. (2007) Mechanisms
and causes of death in 143 Vietnamese HIV-infected patients hospitalized
for tuberculosis. Rev Pneumol Clin 63: 139-46. » CrossRef » PubMed » Google Scholar
- Nikolaeva LG, Maystat TV, Masyuk LA, Pylypchuk VS, Volyanskii YL, et
al. (2008) Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients.
Drug Des Dev Ther 2: 87-93. » CrossRef » PubMed » Google Scholar
- Nikolaeva LG, Maystat TV, Pylypchuk VS, Volyanskiic YL, Masyuk LA, et
al. (2008) Effect of oral immunomodulator Dzherelo (Immunoxel) in TB/
HIV co-infected patients receiving anti-tuberculosis therapy under DOTS.
Intl Immunopharmacol 8: 845-851. » CrossRef » PubMed » Google Scholar
- Prihoda ND, Arjanova OV, Yurchenko LV, Sokolenko1 NI, Vihrova LA, et
al. (2007) Open label trial of adjuvant immunotherapy with Dzherelo,
Svitanok and Lizorm, in MDR-TB, XDR-TB and TB/HIV co-infected patients
receiving anti-tuberculosis therapy under DOT. J Med Plant Res 1:
117-122. » Google Scholar
- Prihoda ND, Arjanova OV, Yurchenko LV, Sokolenko NI, Vihrova LA, et
al. (2008) Adjuvant immunotherapy of tuberculosis in drug-resistant TB and
TB/HIV co-infected patients. Intl J Biomed Pharm Sci 2: 59-64. » Google Scholar
- Saraceni V, King BS, Cavalcante SC, Golub JE, Lauria LM, et al. (2008)
Tuberculosis as primary cause of death among AIDS cases in Rio de Janeiro,
Brazil. Int J Tuberc Lung Dis 12: 769-72. » CrossRef » PubMed » Google Scholar
- Swaminathan S, Deivanayagam CN, Rajasekaran S, Venkatesan P,
Padmapriyadarsini C, et al. (2008) Long term follow up of HIV-infected
patients with tuberculosis treated with 6-month intermittent short course
chemotherapy. Natl Med J India 21: 3-8.» CrossRef » PubMed » Google Scholar
- Wejse C, Gustafson P, Nielsen J, Gomes VF, Aaby P, et al. (2008) TBscore:
Signs and symptoms from tuberculosis patients in a low-resource setting
have predictive value and may be used to assess clinical course. Scand J
Infect Dis 40: 111-20. » CrossRef » PubMed » Google Scholar
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