Correspondence
More on HIV-Associated Kaposi's Sarcoma
N Engl J Med 2008; 358:535-536January 31, 2008
- Article
To the Editor:
The AIDS Malignancy Consortium, a multicenter cooperative group funded by the National Cancer Institute, has enrolled 442 patients who have human immunodeficiency virus (HIV) infection and measurable Kaposi's sarcoma in a series of therapeutic trials since 1996 (Table 1Table 1
Characteristics of Patients with Kaposi's Sarcoma Enrolled in AIDS Malignancy Consortium Trials, 1996–2007.).Our data suggest that persistent Kaposi's sarcoma despite apparently effective antiretroviral therapy is not a rare, isolated, or recent phenomenon, as suggested by Maurer and colleagues in their letter to the editor (Sept. 27 issue).1 On the contrary, our findings indicate that since the introduction of effective antiretroviral therapy, many patients with AIDS-associated Kaposi's sarcoma have CD4 counts above the level typically associated with susceptibility to opportunistic diseases. Furthermore, although effective HIV suppression has been correlated with regression of Kaposi's sarcoma after antiretroviral therapy,2 a substantial proportion of our patients had undetectable HIV viral loads.
These findings raise important questions about the mechanisms that control the progression of human herpesvirus 8 and Kaposi's sarcoma. They also suggest a need for studies to identify clinically relevant correlates that can distinguish between patients whose Kaposi's sarcoma responds to antiretroviral therapy and those who do not have such a response. These factors may include age, duration of HIV infection, human herpesvirus 8 viral load, and patterns of viral gene expression within tumors.
2 ReferencesSusan E. Krown, M.D.
Memorial Sloan-Kettering Cancer Center, New York, NY 10065
krowns@mskc.org Jeannette Y. Lee, Ph.D.
University of Alabama at Birmingham, Birmingham, AL 35294-3300Dirk P. Dittmer, Ph.D.
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290for the AIDS Malignancy Consortium
1
Maurer T ,Ponte M ,Leslie K . HIV-associated Kaposi's sarcoma with a high CD4 count and a low viral load. N Engl J Med 2007;357:1352-1353
Full Text | Web of Science | Medline2
Martinez V ,Caumes E ,Gambotti L , et al. Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy. Br J Cancer 2006;94:1000-1006
CrossRef | Web of Science | Medline
Author/Editor Response
With respect to the comments of Krown and colleagues: we note with interest the number of patients with a CD4 count of 300 per cubic millimeter or more and an undetectable HIV viral load who were enrolled in their therapeutic trials. We have not claimed that what we are observing in San Francisco is an isolated phenomenon and, on the contrary, have suspected it to be more widespread. However, Kaposi's sarcoma remains a striking rarity in published studies1-5 and is not a well-described phenomenon in clinical practice.
It is difficult to compare directly the subjects in the trials by Krown et al. with our patients, since the correspondents have not provided data regarding the duration of the CD4 counts and viral loads, the duration of HIV infection, the CD4 nadirs of the subjects, the temporal relationship with the presentation of Kaposi's sarcoma lesions, and the response to antiretroviral treatment. Our patients have persistent Kaposi's sarcoma despite sustained high CD4 counts and undetectable viral loads for more than 2 years. The median CD4 nadir in our group is 340 per cubic millimeter, with a median duration of HIV infection of 18 years. We encourage Krown et al. and others to publish their data more fully.
5 ReferencesToby Maurer, M.D.
Maya Ponte, M.D., Ph.D.
Kieron Leslie, M.B., B.S., M.R.C.P.
University of California at San Francisco, San Francisco, CA 94110
maurert@derm.ucsf. edu 1
Stebbing J ,Sanitt A ,Nelson M ,Powles T ,Gazzard B ,Bower M . A prognostic index for AIDS-associated Kaposi's sarcoma in the era of highly active antiretroviral therapy. Lancet 2006;367:1495-1502
CrossRef | Web of Science | Medline2
Ledergerber B ,Egger M ,Erard V , et al. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. JAMA 1999;282:2220-2226
CrossRef | Web of Science | Medline3
Mocroft A ,Kirk O ,Clumeck N , et al. The changing pattern of Kaposi sarcoma in patients with HIV, 1994-2003: the EuroSIDA Study. Cancer 2004;100:2644-2654
CrossRef | Web of Science | Medline4
Martinez V ,Caumes E ,Gambotti L , et al. Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy. Br J Cancer 2006;94:1000-1006
CrossRef | Web of Science | Medline5
Nasti G ,Talamini R ,Antinori A , et al. AIDS-related Kaposi's sarcoma: evaluation of potential new prognostic factors and assessment of the AIDS Clinical Trial Group Staging System in the Haart Era -- the Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Naïve from Antiretrovirals. J Clin Oncol 2003;21:2876-2882
CrossRef | Web of Science | Medline
- Citing Articles (12)
Citing Articles
1
Thomas S. Uldrick, Denise Whitby. (2011) Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Letters 305:2, 150-162
CrossRef2
Nancy F Crum-Cianflone, Katherine Huppler Hullsiek, Anuradha Ganesan, Amy Weintrob, Jason F Okulicz, Brian K Agan. (2010) Is Kaposiʼs sarcoma occurring at higher CD4 cell counts over the course of the HIV epidemic?. AIDS 24:18, 2881-2883
CrossRef3
Mary Cianfrocca, Sandra Lee, Jamie Von Roenn, Anil Tulpule, Bruce J. Dezube, David M. Aboulafia, Richard F. Ambinder, Jeannette Y. Lee, Susan E. Krown, Joseph A. Sparano. (2010) Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma. Cancer 116:16, 3969-3977
CrossRef4
T. Ma, B. C. Jham, J. Hu, E. R. Friedman, J. R. Basile, A. Molinolo, A. Sodhi, S. Montaner. (2010) Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi's sarcoma. Proceedings of the National Academy of Sciences 107:32, 14363-14368
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Miguel Rivero Fernández, María García Martos, Patricia Sanz Moya, Manuel Vázquez Romero, María Teresa Fernández Amago, María Teresa García Benayas, Pilar Sánchez-Pobre Bejarano. (2010) Sarcoma de Kaposi con afectación colorrectal y del canal anal. Gastroenterología y Hepatología 33:7, 508-511
CrossRef6
S. Lodi, M. Guiguet, D. Costagliola, M. Fisher, A. de Luca, K. Porter, . (2010) Kaposi Sarcoma Incidence and Survival Among HIV-Infected Homosexual Men After HIV Seroconversion. JNCI Journal of the National Cancer Institute 102:11, 784-792
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Kate Buchacz, Rose K Baker, Frank J Palella, Joan S Chmiel, Kenneth A Lichtenstein, Richard M Novak, Kathleen C Wood, John T Brooks. (2010) AIDS-defining opportunistic illnesses in US patients, 1994–2007: a cohort study. AIDS 24:10, 1549-1559
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Meena Sunil, Erin Reid, Mary Jo Lechowicz. (2010) Update on HHV-8-Associated Malignancies. Current Infectious Disease Reports 12:2, 147-154
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Gary M Clifford, Silvia Franceschi. (2009) Cancer risk in HIV-infected persons: influence of CD4 + count. Future Oncology 5:5, 669-678
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Ravit Arav-Boger. (2009) Treatment for Kaposi sarcoma herpesvirus: great challenges with promising accomplishments. Virus Genes 38:2, 195-203
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Ryan J. Sullivan, Liron Pantanowitz, Corey Casper, Justin Stebbing, Bruce J. Dezube. (2008) HIV/AIDS: Epidemiology, Pathophysiology, and Treatment of Kaposi Sarcoma–Associated Herpesvirus Disease: Kaposi Sarcoma, Primary Effusion Lymphoma, and Multicentric Castleman Disease. Clinical Infectious Diseases 47:9, 1209-1215
CrossRef12
S Franceschi, L Dal Maso, M Rickenbach, J Polesel, B Hirschel, M Cavassini, A Bordoni, L Elzi, S Ess, G Jundt, N Mueller, G M Clifford. (2008) Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy. British Journal of Cancer 99:5, 800-804
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