Jackson David Reynolds, BS, AS

Dalton State College

Kaposi Sarcomain

Immune Reconstitution Inflammatory Syndrome

Figures (clockwise) from: Lavigne et al.,1998; Dalton State College &VisionPoint Marketing, 2016; Kelley L.A., et al., 2015. 1

Kaposi Sarcoma (KS) & HIV/AIDS• Human Herpesvirus type 8 (HHV-8)• Kaposi Sarcoma associated Herpesvirus (KSHV)

• Immunodeficiency• Endothelial cells• Latent/lysogenic• Tumors expansion = angiogenesis

American Cancer Society, Inc., 2016. Figures (clockwise) modified from: Henderson & Physicians Research Network (PRN®), 2002; National Cancer Institute,2001; Silverman, Jr. & Centers for Disease Control and Prevention Public Health Image Library (PHIL), 1999.

2

Cytoplasm Nucleus

KSHV Engenders Angiogenesis via Activationof Proinflammatory Cascades.

Chang et al., 2016. Figure modified from: Chang et al., 2016.

NO

T T

O S

CA

LE

= miR-221/-222 promoter

= cytokine transcripts

Kaposin B

c-myc

KSHV

∴↑[cytokines]cytosolANGIOGENESIS

= miR-221/-222

3

Highly Active Antiretroviral Therapy (HAART)

• Multi-drug approach• Longitudinal treatment• Very effective• Mortality: >30% à <9%

Collier et al., 1996; National Institute on Drug Abuse, 2012; Palella et al., 1998; Riying et al., 2017; Shafer & Vuitton, 1999. Figure from: Splettstoesser, 2013.4

Immune Reconstitution Inflammatory Syndrome (IRIS)

• Iatrogenic (2º to HAART)• CD4+ count rapidly increases• Occult infections suddenly

become violently symptomatic• Severity of symptoms likely*

the result of an Ag-specific T-cell mediated response to occult pathogens

*Detailed MOA not yet entirely elucidated…

Bosamiya, 2011; Kiggundu, Nabeta, Okia, Rhein, & Lukande, 2016; Sharma & Soneja, 2011. Figure modified from: Kiggundu, Nabeta, Okia, Rhein, & Lukande,2016.

5

IRIS in the Context of KS• Rare• Atypical presentation of KS• Pleuropulmonary

• Can be rapidly fatal

Bower et al., 2005; Odongo, 2013; Suresh, Semaan, Arias, Karakousis, & Lee, 2016. Figures modified from: (left & middle) Suresh, Semaan, Arias, Karakousis,& Lee, 2016; (right) Odongo, 2013.

6

IRIS, Statins, & (Possible?) KS Prophylaxis

Drechsler et al., 2017. 7

American Cancer Society, Inc. (2016, February 9). Kaposi Sarcoma. Retrieved February 21, 2017, from http://www.cancer.org/cancer/kaposisarcoma/ detailedguide/kaposi-sarcoma-what-is-key-statistics

Bosamiya, S. (2011). The immune reconstitution inflammatory syndrome. Indian Journal of Dermatology, 56(5), 476. doi:10.4103/0019-5154.87114

Bower, M., Nelson, M., Young, A. M., Thirlwell, C., Newsom-Davis, T., Mandalia, S., . . . Stebbing, J. (2005). Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma. Journal of Clinical Oncology, 23(22), 5224-5228. Retrieved March 6, 2017.

Chang, H., Hsieh, T., Lee, Y., Tsai, C., Tsai, Y., Cheng, C., & Wang, H. (2016). C-Myc and viral cofactor Kaposin B co-operate to elicit angiogenesis through modulating miRNome traits of endothelial cells. BMC Systems Biology, 10(S1). doi:10.1186/s12918-015-0242-3

Collier, A. C., Coombs, R. W., Schoenfeld, D. A., Bassett, R. L., Timpone, J., Baruch, A., . . . Corey, L. (1996). Treatment of Human Immunodeficiency Virus Infection with Saquinavir, Zidovudine, and Zalcitabine. New England Journal of Medicine, 334(16), 1011-1018. doi:10.1056/nejm199604183341602

Dalton State College, & VisionPoint Marketing. (2016). Dalton state logo [Digital image]. Retrieved February 20, 2017, from https://www.daltonstate.edu/skins/userfiles/files/2016-7-27%20DaltonState_BrandGuidelines.pdf

References I

8

Drechsler, H., Ayers, C., Cutrell, J., Maalouf, N., Tebas, P., & Bedimo, R. (2017). Current use of statins reduces risk of HIV rebound on suppressive HAART. Plos One, 12(3). doi:10.1371/journal.pone.0172175

Henderson, L. E., PhD, & Physicians Research Network (PRN®). (2002, March). Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8 (HHV-8), in saliva [Digital image]. Retrieved February 27, 2016, from http://www.prn.org/images/uploads/ kshv_hhv-8_in_saliva_1200_800.jpg

Kiggundu, R., Nabeta, H. W., Okia, R., & Rhein, J. (2016, December 30). Cutaneous lesions throughout on the face before the antifungal treatment. [Digital image]. Retrieved March 6, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304559/figure/g01/

Kiggundu, R., Nabeta, H. W., Okia, R., Rhein, J., & Lukande, R. (2016). Unmasking histoplasmosis immune reconstitution inflammatory syndrome in a patient recently started on antiretroviral therapy. Autopsy and Case Reports, 6(4), 27-33. doi:10.4322/acr.2016.048

Lavigne, P., Crump, M. P., Hodges, R. S., Kay, C. M., Sykes, B. D., & Gagné, S. M. (1998). Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper. Journal of Molecular Biology, 281(1), 165-181. doi:10.1006/jmbi.1998.1914

References II

9

National Cancer Institute. (2001, January 1). Kaposi's sarcoma [Kaposi's sarcoma on the skin of an AIDS patient.]. Retrieved February 27, 2016, from https://visualsonline.cancer.gov/ details.cfm?imageid=2168

National Institute on Drug Abuse. (2012, July). What is HAART? Retrieved March 6, 2017, from https://www.drugabuse.gov/publications/research-reports/hivaids/what-haart

Odongo, F. C. (2013). Fatal disseminated Kaposi's sarcoma due to immune reconstitution inflammatory syndrome following HAART initiation. Case Reports in Infectious Diseases, 2013, 1-3. doi:10.1155/2013/546578

Odongo, F. C. (2013). Figure 2 [Initial chest CT scan at the ICU, revealing bilateral patchy infiltrates suggestive of lung KS or alveolar hemorrhage.]. Retrieved March 6, 2017, from https://www.hindawi.com/journals/criid/2013/546578/fig2/

Palella, F. J., Delaney, K. M., Moorman, A. C., Loveless, M. O., Fuhrer, J., Satten, G. A., . . . Holmberg, S. D. (1998). Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection. New England Journal of Medicine, 338(13), 853-860. doi:10.1056/nejm199803263381301

Riying, L., Guojian, L., Jizhou, W., Yujia, Z., Jianlong, L., Xionglin, Q., . . . Chaoyu, X. (2017). Investigation of the survival time and quantification of therapeutic benefits for HIV patients with highly active antiretroviral therapy. Biomedical Research, 28(1), 279-283. Retrieved February 21, 2017.

References III

10

Shafer, R. W., & Vuitton, D. A. (1999). Highly active antiretroviral therapy (Haart) for the treatment of infection with human immunodeficiency virus type 1. Biomedicine & Pharmacotherapy, 53(2), 73-86. doi:10.1016/s0753-3322(99)80063-8

Sharma, S., & Soneja, M. (2011). HIV & immune reconstitution inflammatory syndrome (IRIS). The Indian Journal of Medical Research, 134(6), 866-877. doi:10.4103/0971-5916.92632

Silverman, S., Jr., DDS, & Centers for Disease Control and Prevention Public Health Image Library (PHIL). (1999). Kaposi sarcoma of the mouth [This HIV-positive patient presented with an intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection.]. Retrieved February 27, 2016, from http://phil.cdc.gov/phil_images/ 20040819/5/072_lores.jpg

Splettstoesser, T. (2013, November 6). HIV-drug-classes [Schematic description of the mechanism of the four classes of currently available antiviral drugs against HIV: fusion inhibitors ( interfere with the binding, fusion or entry of an HIV virion), reverse-transcriptase inhibitors (interfere with the translation of viral RNA into DNA), integrase inhibitors (block the viral enzyme integrase, that inserts the viral genome into the DNA of the host cell), protease inhibitors (block proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles)]. Retrieved February 21, 2017, from https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg

References IV

11

Suresh, K., Semaan, R., Arias, S., Karakousis, P., & Lee, H. (2016, May 30). Figure 1 [Pleural KS lesions.]. Retrieved March 6, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943458/figure/F1/

Suresh, K., Semaan, R., Arias, S., Karakousis, P., & Lee, H. (2016). Pleuropulmonary Kaposi sarcoma in the setting of immune reactivation. Journal of Pulmonary & Respiratory Medicine, 6(3). doi:10.4172/2161-105x.1000352

Vanable, P. A., Ostrow, D. G., Mckirnan, D. J., Taywaditep, K. J., & Hope, B. A. (2000). Impact of combination therapies on HIV risk perceptions and sexual risk among HIV-positive and HIV-negative gay and bisexual men. Health Psychology, 19(2), 134-145. doi:10.1037//0278-6133.19.2.134

References V

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