What is the role of antiretroviral therapy in the treatment of Kaposi sarcoma (KS)?

Updated: Apr 11, 2019
  • Author: Jessica Katz, MD, PhD, FACP; Chief Editor: Edwin Choy, MD, PhD  more...
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Answer

Antiretroviral therapy for AIDS-related Kaposi sarcoma

Optimal control of HIV infection using HAART is an integral part of therapy for AIDS-related Kaposi sarcoma, and should be the first step in therapy. Response to HAART can range from 20-80%, depending on the stage of disease and the amount of pretreatment. [83]  Since its inception, HAART has changed the therapeutic goal in Kaposi sarcoma from short-term palliation to long-term remission and control.

Effective combination antiretroviral therapy usually comprises a combination of either a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) with 2 nucleoside reverse transcriptase inhibitos (NRTIs). Some evidence suggests a direct antitumor effect on angioproliferative Kaposi sarcoma–type lesions, but to date no level 1 evidence supports this clinically. [84]  No difference is apparent between PI-based and NNRTI-based antiretroviral regimens in terms of response of Kaposi sarcoma. [69]

HAART may be tried as the sole modality in nonvisceral disease. For visceral disease, chemotherapy may be added. For locally symptomatic disease, radiation therapy may be introduced. [31]

However, patients with poor-risk Kaposi sarcoma rarely respond to HAART alone. In addition, approximately 6-39% of patients with AIDS-related Kaposi sarcoma develop immune reconstitution inflammatory syndrome (IRIS) with worsening of Kaposi sarcoma within 3 to 6 months after re-initiating ART. [85]  This occurs in association with increase in CD4 counts and control of HIV viremia. [85, 76] The criteria for Kaposi sarcoma IRIS per the AIDS Clinical Trial Group are as follows:

  • Onset after starting, restarting, or altering of the HAART regimen
  • Increase of CD4 count by ≥50 cells/μL or a 2-fold increase in CD4 count, and decrease in HIV-1 viral load of greater than 0.5 log
  • More-than-expected progression of Kaposi sarcoma within 12 weeks of initiating HAART

Risk factors for Kaposi sarcoma–associated IRIS include pulmonary involvement, concurrent or recent use of glucocorticoids, and advanced immunosuppression. Glucocorticoids are generally contraindicated in Kaposi sarcoma due to their stimulatory effect on Kaposi sarcoma spindle cells. [86]  In this clinical situation, chemotherapy may be necessary to ameliorate and reverse the disease progression.

The choice of therapy beyond HAART must be individualized and depends on the extent of disease, the presence and nature of the symptoms, the rate of disease progression, and the overall therapeutic goals. 

Palliative systemic therapy is indicated for symptomatic or life-threatening visceral disease, rapidly progressive mucocutaneous disease with pain or ulceration, and symptomatic lymphedema. In this setting, few reliable estimates of response rate with HAART alone compared with combined HAART and chemotherapy are available. One trial from South Africa reported response rates of 39% to HAART alone versus 66% to HAART plus chemotherapy; in addition,, 35% of patients in the HAART arm crossed over to require palliative chemotherapy or radiation within 12 months of randomization. These results support the use of chemotherapy combined with HAART in patients with high tumor volume (T1). [87]


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