One-month immunotherapy trial in treatment-failed TB patients

Olga V. Arjanova, Dmitry A. Butov, Natalia D. Prihoda, Svetlana I. Zaitzeva, Larisa V. Yurchenko, Nina I. Sokolenko, Anna L. Stepanenko, Tatyana S. Butova, Elena A. Grinishina, Olga A. Maksimenko, Vichai Jirathitikal, Aldar S. Bourinbaiar, Valery M. Frolov, Galyna A. Kutsyna

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DOI: 10.4236/oji.2011.12006                

Abstract

reatment failed TB patients have very limited chances of survival. Open label trial of daily oral pill of V-5 Immunitor (V5) was conducted in 48 treatment-failed TB patients on palliative support consisting of isoniazid (H) and rifampicin (R). The subjects had the following forms of TB; cavitary: disseminated: MDR-TB: DR-TB: TB/HIV at 35:13:7:4:1 ratio. After 1 month 62.5% of V5-treated patients experienced negative sputum smear conversion (P < 0.0001), comprising 11 out of 12 (91.7%) converted among those who had drug-resistant TB and TB/HIV. TB-associated inflammation was downregulated as evidenced by normalization of leukocytosis 7.4 vs. 6.7 x 109 L (P = 0.01) and decreased erythrocyte sedimentation rate 20.5 vs. 14.9 mm/h (P < 0.0001). The mean body temperature normalized from 37.25° ± 0.6° to 36.98° ± 0.4° (P = 0.0002). The average body weight gain and body mass index (BMI) increased by 0.8 ± 0.7 kg and from 18.9 to 19.6 kg/m² respectively (P < 0.0001). Two patients (4.2%) died from illicit drug- and alcohol-abuse related causes. No adverse effects or reactivation of disease due to immune intervention were seen at any time. V5 is safe and in combination with a simple two-drug regimen was highly effective as an immune adjunct to produce favorable outcome among treatment-failed and/ or drug-resistant TB patients.

Keywords

Biomarker; HIV; Inflammation; MDR-TB; Mycobacterium; Survival; Treatment Failure; Vaccine

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Lienhardt, C., Vernon, A. and Raviglione, M.C. (2010) New drugs and new regimens for the treatment of tuberculosis: Review of the drug development pipeline and implications for national programmes. Current Opinion in Pulmonary Medicine, 16, 186-193. doi:10.1097/MCP.0b013e328337580c
[2]	Tiemersma, E.W., van der Werf, M.J., Borgdorff, M.W., Williams, B.G. and Nagelkerke, N.J. (2011) Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: A systematic review. PLoS One, 6, e17601. doi:10.1371/journal.pone.0017601
[3]	Goble, M., Iseman, M.D., Madsen, L.A., Waite, D., Ackerson, L. and Horsburgh, C.R. Jr. (1993) Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. New England Journal of Medicine, 328, 527-532. doi:10.1056/NEJM19930225328080
[4]	Churchyard, D.J. (2007) Report of the expert consultation on immunotherapeutic interventions for tuberculosis. TDR/World Health Organization, Geneva, Switzerland. http://apps.who.int/tdr/publications/tdr-research-publications/immunotherapeutic-interventions-tb/pdf/interventions-tb.pdf
[5]	Batdelger, D., Dandii, D., Jirathitikal, V. and Bourinbaiar, A.S. (2007) Open label trial of therapeutic hepatitis B vaccine V-5 Immu-nitor (V5) delivered by oral route. Letters in Drug Design and Discovery, 4, 540-544, 2007. doi:10.2174/157018007782794545
[6]	Batdelger, D., Dandii, D., Jirathitikal, V. and Bourinbaiar, A.S. (2008) Open label trial of therapeutic immunization with oral V-5 Immunitor (V5) vaccine in patients with chronic hepatitis C. Vaccine, 26, 2733-2737. doi:10.1016/j.vaccine.2008.03.021
[7]	Batdelger, D., Dandii, D., Dahgwahdorj, Ya., Erdenetsogt, E., Oyunbileg, J., Tsend, N., Bayarmagnai, B., Jirathitikal, V. and Bourin-baiar, A.S. (2009) Clinical experience with therapeutic vaccines designed for patients with hepatitis. Current Pharmaceutical Design, 15, 1159-1171. doi:10.2174/138161209787846793
[8]	Arjanova, O.V., Prihoda, N.D., Yurchenko, L.V., Sokolenko, N.I., Frolov, V.M., Tarakanovskaya, M.G., Jirathitikal, V. and Bourin-baiar, A.S. (2010) Phase 2 trial of V-5 Immunitor (V5) in patients with chronic hepatitis C co-infected with HIV and Mycobacterium tuberculosis. Journal of Vaccines and Vaccination, 1, 103. doi:10.4172/2157-7560.1000103
[9]	Butov, D.A., Pashkov, Y.N., Stepanenko, A.L., Choporova, A.I., Butova, T.S., Batdelger, D., Jirathitikal, V., Bourinbaiar, A.S. and Zaitzeva, S.I. (2011) Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi- drug-resistant (MDR) TB. Journal of Immune Based Therapies and Vaccines, 9, 3. doi:10.1186/1476-8518-9-3
[10]	Arjanova, O.V., Prihoda, N.D., Yurchenko, L.V., Sokolenko, N.I., Frolov, V.M., Tarakanovskaya, M.G., Batdelger, D., Jirathitikal, V. and Bourinbaiar, A.S. (2011) Adjunct oral immunotherapy in patients with re-treated, multidrug-resistant or HIV-coinfected TB. Im-munotherapy, 3, 181-191. doi:10.2217/imt.10.96
[11]	Nuermberger, E.L., Spigelman, M.K. and Yew, W.W. (2010) Current development and future prospects in chemotherapy of tubercu-losis. Respirology, 15, 764-778. doi:10.1111/j.1440-1843.2010.01775.x
[12]	Becerra, M.C., Freeman, J., Bayona, J., Shin, S.S., Kim, J.Y., Furin, J.J., Werner, B., Sloutsky, A., Timperi, R., Wilson, M.E., Pagano, M. and Farmer, P.E. (2000) Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis. International Journal of Tuberculosis and Lung Diseases, 4, 108-114. PMid:10694087
[13]	Johnston, J.C., Shahidi, N.C., Sadatsafavi, M. and Fitzgerald, J.M. (2009) Treatment outcomes of multidrug- resistant tuberculosis: a systematic review and meta- analysis. PLoS One, 4, e6914. doi:10.1371/journal.pone.0006914
[14]	Faustini, A., Hall, A.J. and Perucci, C.A. (2005) Tuber- culosis treatment outcomes in Europe: a systematic re- view. European Res-piratory Journal, 26, 503-510. doi:10.1183/09031936.05.00103504
[15]	Khan, A., Sterling, T.R., Reves, R., Vernon, A. and Horsburgh, C.R. (2006) Lack of weight gain and relapse risk in a large tuberculo-sis treatment trial. American Journal of Respiratory and Critical Care Medicine, 174, 344-348. doi:10.1164/rccm.200511-1834OC
[16]	Bernabe-Ortiz, A., Carcamo, C.P., Sanchez, J.F. and Rios, J. (2011) Weight variation over time and its association with tuberculosis treatment outcome: a longitudinal analysis. PLoS One, 6, e18474. doi:10.1371/journal.pone.0018474
[17]	Zafran, N., Heldal, E., Pavlovic, S., Vuckovic, D. and Boe, J. (1994) Why do our patients die of active tuberculosis in the era of ef-fective therapy? Tuberculosis and Lung Disease, 75, 329-333. doi:10.1016/0962-8479(94)90077-9
[18]	Franke, M.F., Appleton, S.C., Bayona, J., Arteaga, F., Palacios, E., Llaro, K., Shin, S.S., Becerra, M.C., Murray, M.B. and Mitnick, C.D. (2008) Risk factors and mortality associated with default from multidrug-resistant tuberculosis treatment. Clinical Infectious Diseases, 46, 1844-1851. doi:10.1086/588292
[19]	Akintunde, E.O., Shokunbi, W.A. and Adekunle, C.O. (1995) Leucocyte count, platelet count and erythrocyte sedimentation rate in pulmonary tuberculosis. African Journal of Medicine and Medical Science, 24, 131-134. PMid:8669390
[20]	Barnes, P.F. (2003) Immunotherapy for tuberculosis: wave of the future or tilting at windmills? American Journal of Respiratory and Critical Care Medicine, 168, 142-143. doi:10.1164/rccm.2305001
[21]	Churchyard, GJ, Kaplan, G, Fallows, D, Wallis, RS, Onyebujoh, P. and Rook, GA. (2009) Advances in immunotherapy for tuberculo-sis treatment. Clinical Chest Medicine, 30, 769-782. doi:10.1016/j.ccm.2009.08.009
[22]	Dheda, K., Schwander, S.K., Zhu, B., van Zyl-Smit, R.N. and Zhang, Y. (2010) The immunology of tuberculosis: from bench to bed-side. Respirology, 15, 433-450. doi:10.1111/j.1440-1843.2010.01739.x
[23]	Grange, J.M., Brunet, L.R. and Rieder, H.L. (2011) Immune protection against tuberculosis-when is immunotherapy preferable to vaccination? Tuberculosis, 91, 179-185. doi:10.1016/j.tube.2010.12.004
[24]	Silin, D.S., Lyubomska, O.V., Ershov, F.I., Frolov, V.M. and Kutsyna, G.A. (2009) Immunomodulators with interferon inducing properties. Current Pharmaceutical Design, 15, 1238-1247. doi:10.2174/138161209787846847
[25]	Arjanova, O.V., Prihoda, N.D., Sokolenko, N.I., Yurchenko, L.V., Vihrova, L.A., Pylypchuk, V.S., Frolov, V.M. and Kutsyna, G.A. (2009) Impact of adjunct immunotherapy with multi-herbal supplement Dzherelo (Immunoxel) on treatment outcomes in end-stage TB/HIV patients. Journal of Antivirals and Antiretrovirals, 1, 86-88. doi:10.4172/jaa.1000013
[26]	Stanford, J., Stanford, C. and Grange, J. (2004) Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis. Fron-tiers in Bioscience, 9, 1701-1719. doi:10.2741/1292