Autologous Peripheral Blood Stem Cells and γ/δ T Cells May Improve Immunity in Treating Secondary Bacteremic Infection in HIV Infected Patient

Ciro Gargiulo^1*, Van Hung Pham², Nguyen Thuy Hai¹, Kieu C. D. Nguyen³, Ngan Duong Kim¹, Thinh Nguyen Van¹, An Luu Tuan¹, Kenji Abe⁴, Veronica Flores⁵, Melvin Shiffman⁶

¹Division of Internal Medicine, The Human Medicine International Clinic, Ho Chi Minh City, Vietnam.
²Molecular Diagnostics Department, Nam Khoa-Biotek Laboratory, Ho Chi Minh City, Vietnam.
³Division of Pathology, The Human Medicine International Clinic, Ho Chi Minh City, Vietnam.
⁴Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japa.
⁵Sol Price School of Public Policy, University of Southern California, Los Angeles, CA, USA.
⁶Section of Surgery, Newport Specialty Hospital, Tustin, CA, USA.

DOI: 10.4236/scd.2015.54006                

Abstract

Opportunistic bacteremia in adult HIV-infected patients is a normal co-infectious condition caused by Gram-negative bacilli. Respiratory infections, including cough, shortness of breath, and chest pain and skin infection with eruptions, pustules and itchiness, are common complaints in the setting of late HIV infection. The variety of infections ranges from mild, self-limited viral, bacteremia and fungal infections to severe, life-threatening demanding urgent care and hospitalization. Varicella pneumonia, for instance, is the most severe complication of chickenpox in HIV infected adults, potentially refractory, fulminant respiratory failure can ensue. Patients with impaired immune status and chronic lung disease are at an increased risk. In the United States as well as in Vietnam, bacterial/viral pneumonia and skin infection are the two most common HIV-associated conditions. While globally the incidence of opportunistic infection has decreased since the introduction of highly active antiretroviral therapy during the last 3 decades, HIV-associated diseases remain a significant source of mortality, thus any manifestation must be taken seriously. This study will present the most common HIV-related pulmonary and skin infections and provide an overview of the epidemiology, characteristic clinical and chest radiograph findings, diagnosis, treatment, and prevention globally as well in Vietnam. Though the extensive efforts of the Vietnamese Government during last decade contributed to a valuable decrease, yet epidemic in Vietnam still remains high, ranking Vietnam 5^th in the South-East region. The second part of the study focuses on a unique and severe HIV case report of a 35-year-old man, with a rare form of pneumonia caused by Acitenobacter spp. concomitant with a prolonged and disseminating skin infection. The case has been treated with a combination of conventional anti-retroviral medication and autologous peripheral blood stem cells, the results showed that within 5 months there was an impressive amelioration of HIV viral activity together with a total recovery from pneumonia and skin infection.

Keywords

Human Peripheral Blood Stem Cells, γ/δ T Cells, NK Cells, Hematopoietic Stem Cells, CD4, CD8, HIV

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Mootsikapun, P. (2007) Bacteremia in Adult Patients with Acquired Immunodeficiency Syndrome in the Northeast of Thailand. International Journal of Infectious Disease, 11, 226-231. http://dx.doi.org/10.1016/j.ijid.2006.02.010
[2]	Krumholz, H.M., Sande, M.A. and Lo, B. (1989) Community-Acquired Bacteremia in Patients with Acquired Immunodeficiency Syndrome: Clinical Presentation, Bacteriology, and Outcome. American Journal of Medicine, 86, 776-779. http://dx.doi.org/10.1016/0002-9343(89)90472-5
[3]	Manfredi, R., Cosiglioga, P., Ricchi, E. and Chiodo, F. (1993) Sepsis-Bacteremia and Other Infections Due to Non-Opportunistic Bacterial Pathogens in a Consecutive Series of 788 Patients Hospitalized for HIV Infection. Clinical Therapeutics, 143, 279-290.
[4]	Tumbarello, M., Tacconelli, E., Caponera, S., Cauda, R. and Ortona, L. (1995) The Impact of Bacteremia on HIV Infection. Nine Years Experience in a Large Italian University Hospital. Journal of Infection, 31, 123-131. http://dx.doi.org/10.1016/S0163-4453(95)92110-9
[5]	Kovacs, A., Leaf, H.L. and Simberkoff, M.S. (1997) Bacterial Infections. Medical Clinics of North America, 81, 319-343. http://dx.doi.org/10.1016/S0025-7125(05)70520-4
[6]	Huang, L. and Crothers, K.A. (2010) HIV-Associated Pneumonias. NIH, 1-19.
[7]	Fichtenbaum, C.J., Dunagan, W.C. and Powderly, W.G. (1995) Bacteremia in Hospita-lized Patients Infected with HIV: A Case Control Study of Risk Factors and Outcome. Journal of Acquired Immune Deficiency Syndrome, 8, 51-57.
[8]	Tumbarello, M., Tacconelli, E., de Gaetano Donati, K., Leone, F., Morace, G., Cauda, R. and Ortona, L. (1998) Nosocomial Bloodstream Infections in HIV-Infected Patient: Attributable Mortality and Excess Hospital Stay. Journal of Acquired Immune Deficiency Syndrome & Human Retrovirology, 19, 490-496. http://dx.doi.org/10.1097/00042560-199812150-00008
[9]	Afessa, B., Morales, I. and Weaver, B. (2001) Bacteremia in Hospitalized Patient with Human Immunedeficiency Virus: A Prospective Cohort Study. BMC Infectious Diseases, 1, 1-13. http://dx.doi.org/10.1186/1471-2334-1-13
[10]	Whimbey, E., Gold, J.W., Polsky, B., Dryjanski, J., Hawkins, C., Blevins, A., Brannon, P., Kiehn, T.E., Brown, A.E. and Armstrong, D. (1986) Bacteremia and Fungemia in Patients with the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine, 104, 511-514. http://dx.doi.org/10.7326/0003-4819-104-4-511
[11]	Bouza, E. and Rodriguez-Creixems, M. (1999) Bacteremic Infection in the HIV Infected Patients and Recurrent Bacteremia. Clinical Microbiology and Infections, 5, 2s33-2s39.
[12]	Ashkenazi, S., Leibovici, L., Samra, Z., Konisberger, H. and Drucker, M. (1992) Risk Factors for Mortality Due to Bacteremia and Fungemia in Childhood. Clinical Infectious Disease, 14, 949-951. http://dx.doi.org/10.1093/clinids/14.4.949
[13]	Manfredi, R., Cosiglioga, P., Ricchi, E. and Chiodo, F. (2001) Pathogenic Role of Acinetobacter Spp during HIV Infection. Infezione Medicale, 9, 43-51.
[14]	Manfredi, R., Cosiglioga, P., Ricchi, E. and Chiodo, F. (2001) Acinetobacter Infections in Patients with Human Immunodeficiency Virus Infection: Microbiological and Clinical Epidemiology. Chemotherapy, 47, 19-28. http://dx.doi.org/10.1159/000048497
[15]	(2014) Vietnam AIDS Response Report 2014: Following up the 2011 Political Declaration on HIV AIDS. 1-118.
[16]	Beyer, C. (2007) HIV Epidemiology Update and Transmission Factors: Risks and Risk Contexts—16th International AIDS Conference Epidemiology Plenary. Clinical Infectious Disease, 44, 981-987. http://dx.doi.org/10.1086/512371
[17]	Aceijas, C., Stimson, G.V., Hickman, M. and Rhodes, T. (2004) Global Overview of Injecting Drug Use and HIV Infection among Injecting Drug Users. AIDS, 18, 2295-2303. http://dx.doi.org/10.1097/00002030-200411190-00010
[18]	Zamani, S., Kihara, M., Gouya, M.M., Vazirian, M., Nassirimanesh, B., Ono-Kihara, M., et al. (2006) High Prevalence of HIV Infection Associated with Incarceration among Community-Based Injecting Drug Users in Tehran, Iran. Journal of Acquired Immune Deficiency Syndrome, 42, 342-346. http://dx.doi.org/10.1097/01.qai.0000219785.81163.67
[19]	United Nations’ Office on Drugs and Crime (UNODC) (2006) World Drug Report for 2005. United Nations Publications, New York.
[20]	Gargiulo, C., Pham, V.H., Nguyen, T.H., Nguyen, C.D.K., Phuc, P.V., Abe, K., Flores, V. and Shiffman, M. (2015) Isolation and Characterization of Multipotent and Pluripotent Stem Cells from Human Peripheral Blood. Journal of Stem Cells Development, 5, 1-16. http://dx.doi.org/10.4236/scd.2015.53003
[21]	Thierry, G., Rubinstein, D.B. and Symann, M. (1992) Immune Reconstitution and Immunotherapy after Autologous Hematopoietic Stem Cell Transplantation. Blood, 92, 1471-1490.
[22]	Philip, T., Guglielmi, C., Hagenbeek, A., Somers, R., Van Der Lelie, H., Bron, D., Sonneveld, P., Gisselbrecht, C., Cahn, J.-Y., Harousseau, J.-L., Coiffier, B., Biron, P., Mandelli, F. and Chauvin, F. (1995) Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin’s Lymphoma. New England Journal of Medicine, 333, 1540-1545. http://dx.doi.org/10.1056/NEJM199512073332305
[23]	Zittoun, R.A., Mandelli, F., Willemze, R., De Witte, T., Labar, B., Resegotti, L., Leoni, F., Damasio, E., Visani, G., Papa, G., Caronia, F., Hayat, M., Stryckmans, P., Rotoli, B., Leoni, P., Peetermans, M.E., Dardenne, M., Vegna, M.L., Petti, M.C., Solbu, G. and Suciu, S. (1995) Autologous or Allogeneic Bone Marrow Transplantation Compared with Intensive Chemotherapy in Acute Myelogenous Leukemia. New England Journal of Medicine, 332, 217-223. http://dx.doi.org/10.1056/NEJM199501263320403
[24]	Attal, M., Harousseau, J.L., Stoppa, A.M., Sotto, J.J., Fuzibet, J.G., Rossi, J.F., Casassus, P., Maisonneuve, H., Facon, T., Ifrah, N., Payen, C. and Bataille, R. (1996) A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma. New England Journal of Medicine, 335, 91-97. http://dx.doi.org/10.1056/NEJM199607113350204
[25]	Humblet, Y., Symann, M., Bosly, A., Delaunois, L., Francis, C., Machiels, J., Beauduin, M., Doyen, C., Weynants, P., Longueville, J. and Prignot, J. (1987) Late Intensification Chemotherapy with Autologous Bone Marrow Transplantation in Selected Small Cell Carcinoma of the Lung: A Randomized Study. Journal of Clinical Oncology, 5, 1864-1873.
[26]	Bezwoda, W.R., Seymour, L. and Dansey, R.D. (1995) High-Dose Chemotherapy with Hematopoietic Rescue as Primary Treatment for Metastatic Breast Cancer: A Randomized Trial. Journal of Clinical Oncology, 13, 2483-2489.
[27]	Damiani, D., Stocchi, R., Masolini, P., Michelutti, A., Sperotto, A., Geromin, A., Skert, C., Cerno, M., Michieli, M., Baccarani, M. and Fanin, R. (2001) Dendric Cells Recover after Autologous Stem Cell Transplantation. Bone Marrow Transplantation, 30, 261-266. http://dx.doi.org/10.1038/sj.bmt.1703637
[28]	Di Nicola, M. and Lemoli, R.M. (2000) Dendritic Cells: Specialized Antigen Presenting Cells. Haematologica, 85, 202-207.
[29]	Bachereau, T. and Steinman, R.M. (1998) Dendritic Cells and the Control of Immunity. Nature, 392, 245-252. http://dx.doi.org/10.1038/32588
[30]	Patel, A.N. and Genovese, J. (2011) Potential Clinical Applications of Adult Human Mesenchymal Stem Cell (Prochymal®) Therapy. Stem Cells and Cloning: Advances and Applications, 4, 61-72.
[31]	Matsubara, H., Makimoto, A., Takayama, J., Higa, T., Saito, T., Kanda, Y., Tanosaki, R., Mineishi, S., Ohira, M. and Takaue, Y. (2001) Possible Clinical Benefits of the Use of Peripheral Blood Stem Cells Over Bone Marrow in the Allogeneic Transplantation Setting for the Treatment of Childhood Leukemia. Japanese Journal of Clinical Oncology, 31, 30-34. http://dx.doi.org/10.1093/jjco/hye001
[32]	Girardi, M. (2006) Immune Surveillance and Immune Regulation by γ/δ T Cells. Journal of Investigative Dermatology, 126, 25-31. http://dx.doi.org/10.1038/sj.jid.5700003
[33]	Chen, Z.W. and Letvin, N.L. (2003) Vγ2Vδ2+ T Cells and Anti-Microbial Immune Responses. Microbes and Infection, 5, 491-498. http://dx.doi.org/10.1016/S1286-4579(03)00074-1
[34]	Kabelitz, D., Marischen, L., Oberg, H.H., Holtmeier, W. and Wesch, D. (2005) Epithelial Defense by γδ T Cells. International Archive of Allergy and Immunology, 137, 73-81. http://dx.doi.org/10.1159/000085107
[35]	Smith, A.L. and Hayday, A.C. (2000) An αβ T-Cell-Independent Immunoprotective Response towards Gut Coccidia Is Supported by γδ Cells. Immunology, 101, 325-332. http://dx.doi.org/10.1046/j.1365-2567.2000.00122.x
[36]	Brandes, M., Willimann, K. and Moser, B. (2005) Professional Antigen-Presentation Function by Human γδ T Cells. Science, 309, 264-268. http://dx.doi.org/10.1126/science.1110267
[37]	Béziat, V., Duffy, D., Nguyen Quoc, S., Le Garff-Tavernier, M., Decocq, J., Combadière, B., Debré, P. and Vieillard, V. (2011) CD56BrightCD16+ NK Cells: A Functional Intermediate Stage of NK Cell Differentiation. Journal of Immunology, 186, 6753-6761. http://dx.doi.org/10.4049/jimmunol.1100330
[38]	Jiang, Y.J., Cui, X.J., Cui, C., Zhang, J., Zhou, F.Y., Zhang, Z.N., Fu, Y.J., Xu, J.J., Chu, Z.X., Liu, J., Han, X.X., Liao, C., Wang, Y., Cao, Y.M. and Shang, H. (2014) The Function of CD3+, CD56+ NKT-Like Cells in HIV-Infected Individuals. BioMedResearch International, 2014, Article ID: 863625.
[39]	Montoya, C.J., Velilla, P.A., Chougnet, C., Landay, A.L. and Rugeles, M.T. (2006) Increased IFN-γ Production by NK and CD3+/CD56+ Cells in Sexually HIV-1-Exposed but Uninfected Individuals. Clinical Immunology, 120, 138-146. http://dx.doi.org/10.1016/j.clim.2006.02.008
[40]	Bocelli-Tyndall, C., Zajac, P. and Di Maggio, N. (2010) Fibroblast Growth Factor 2 and Platelet-Derived Growth Factor, but Not Platelet Lysate, Induce Proliferation-Dependent, Functional Class II Major Histocompatibility Complex Antigen in Human Mesenchymal Stem Cells. Arthritis and Rheumatology, 62, 3815-3825. http://dx.doi.org/10.1002/art.27736
[41]	Tarte, K., Gaillard, J. and Lataillade, J.J. (2010) Clinical-Grade Production of Human Mesenchymal Stromal Cells: Occurrence of Aneuploidy without Transformation. Blood, 115, 1549-1553. http://dx.doi.org/10.1182/blood-2009-05-219907