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Unremitting Kaposi Sarcoma in HIV infected patients with viral suppression on antiretrovirals
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Reported by Jules Levin
ICAAC/IDSA Oct 28 2008 Wash DC
Maya Ponte MD PhD, Kieron Leslie MD, Nicole Wellman MD, Patrick Unemori MD, Toby Maurer MD, University of California San Francisco
from Jules: I spoke with author at ICAAC and she believes that the mild KS is emerging due to patients aging and along with the aging process is a less effective immune system. They are expecting further study results examining these questions.
ABSTRACT
Background: Since the development of antiretroviral therapy (ART), Kaposi's sarcoma (KS) has rarely been noted in individuals with CD4 counts greater than 150 cells/νL or viral loads less than 10,000 copies/ml.
Objective: To describe the presentation and clinical course of ten HIV-positive men who developed KS despite a high CD4 count and low viral load.
Design: A retrospective review
Measurements: Serial CD4 counts, viral loads, lesion number and locations.
Results: All were on ART at the time of KS diagnosis and currently. None have evidence of visceral involvement or other opportunistic infections. Their KS has remained indolent and stable.
Conclusions: These patients represent an atypical expression of KS that occurs despite high CD4 count and low viral load.
Background: Kaposi sarcoma (KS) is a multifocal angiogenic tumor that is associated with the HHV-8 virus and immunosuppression. In large cohort studies, development of KS in patients with HIV is usually associated with low CD4 count (23-129 cells/νl3), high viral load (85,570 to 176,000copies/ml) and low CD4 nadir (upper range of 150 cells/νl, with a median of 78 cells/νl.3). Currently, the mainstay of treatment for KS is to maximize ART with respect to CD4 count and viral load.
We initially reported on a cluster of nine men who had persistent KS despite high CD4 count and low viral load. Since then, we have identified 16 individuals with HIV who have persistent KS despite a sustained CD4 count above 300 cells/νl and viral load suppression below 300 copies/ml over a two-year period of time. These patients exhibit a course that is atypical from the usual course of HIV-related KS in that there is no evidence of immunologic failure. For the purposes of this poster we have decided to focus on 10 of these 16 individuals who had well-controlled HIV with high CD4 count and low viral load at the time they developed KS. Despite adequate ART, the patients in this series have unremitting, though indolent, KS.
Methods: The patients in this series were referred to our practice at a specialized dermatology clinic in a university setting in San Francisco from November of 2004 to July of 2008. IRB approval was obtained from the University of California, San Francisco Institutional Review Board (IRB), and a retrospective review of medical records, including laboratory results, was conducted. Prospectively, serial CD4 counts and viral loads were collected through a collaboration with the UCSF SCOPE study. All subjects had biopsy proven KS.
Results: Our patients include 10 homosexual men. The median was 59 years (42-76 years). The median known duration of HIV was 17 years (6-27 years). 9/10 patients had at least one KS lesion on their lower extremeties, and 7/10 had lesions only on their lower extremeties. In addition to cutaneous KS, one had lymph node involvement, and three had mild edema. Two patients reported pain or discomfort from KS lesions occurring on their feet. None had symptoms or signs of visceral KS at presentation and none have developed them since. The median duration of KS is 2.5 years (1 - 4.5).
Nine out of ten were on ART at the time of KS diagnosis and all are on ART currently. The median length of time of antiretroviral therapy (ART) that includes a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) is 4.5 years (range 1 - 12 years). Two were on a PI-containing regimen at the time of development of KS and five were started on PI-containing regimens after the development of KS. Among those who have not undergone surgical excision, cryotherapy, or treatment with chemotherapeutic agents, the disease has remained fairly stable regardless of whether a PI or NNRTI containing ART regimen has been employed.
Three patients have undergone successful surgical excision of at least one KS lesion. One patient has experienced mild improvement with intralesional vinblastine. Two patients have received radiotherapy resulting in regression of lesions. One patient received liposomal doxorubicin infusions which decreased the number, size, and pigmentation of KS lesions. Three of four patients who have applied topical alitretinoin twice daily have experienced mild improvement. None of the patients have had eruptive KS, organ involvement of KS or development of other opportunistic infections.
Patients similar to ours have been described in the literature before. For example, Chan et al reported the development of KS in two patients treated with HIV on ART despite suppression of viral load below the level of quantitation for at least 7 months. Both of these patients had a CD4 count of greater than 400 at the time of diagnosis with KS. Likewise, Nasti reported that among 211 patients, 10 had an undetectable viral load at the time of KS diagnosis. Martinez's cohort included four patients who had an undetectable viral load at the time of KS diagnosis. These two retrospective cohort studies also noted rare KS subjects with CD4 counts as high as 1117. More recently, Krown et al have reported on the existence of KS patients with HIV who also have high CD4 count and low viral load. These observations indicate that what we are describing is not an isolated phenomena but perhaps a more widespread alteration in the landscape of KS and its relationship to HIV particularly in patients with long term, well-controlled HIV.
Conclusions: We believe that the patients in this series represent an atypical expression of KS that occurs despite viral suppression and good immune system function as measured by CD4 count and viral load. The indolent course and location of lesions resembles classic KS. Given that these individuals are already maximized on their ART, the presence of KS in this population presents a clinical and prognostic conundrum. Based on our preliminary experience with these patients, it is our recommendation that they should be managed conservatively. First, the ART regimen should be reexamined to ensure maximum adherence. Given our observations so far, we do not believe that PIs provide any benefit over NNRTIs in the treatment of this form of KS. Second, we recommend radiation and/or chemotherapy (intralesional or systemic) only when lesions are painful or are located in areas that are highly visible and affect the patient's self image. Finally, given the stigma associated with KS as an AIDS-defining illness, it is important to provide reassurance to patients who develop KS despite high CD4 count and low viral load on ART that this form of KS seems to run a more indolent course despite its unremitting nature.
References:
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(13):1352-3.
Chan J, Kravcik S, Angel JB. Development of Kaposi's sarcoma despite sustained suppression of HIV plasma viremia. J Acquir Immune Defic Syndr 1999;22(2):209-10.
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 Naive From Antiretrovirals. J Clin Oncol 2003;21(15):2876-82.
Nasti G, Martellotta F, Berretta M, et al. Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer 2003;98(11):2440-6.
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(9521):1495-502.
Krown SE, Lee JY, Dittmer DP. More on HIV-associated Kaposi's sarcoma. N Engl J Med 2008;358(5):535-6; author reply
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