Switching from Protease Inhibitors to NNRTIs Is a Potential Risk Factor for Kaposi Sarcoma Relapse

The widespread use of protease inhibitor (PI)-based HAART has led to a steady decline in the incidence of Kaposi sarcoma (KS), as well as tumor regression in individual cases. Conversely, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have been implicated in KS relapse [1,2].

Red and brownish bilateral plaques presenting as a classical Kaposi sarcoma in a 59-year-old male.

In the current cross-sectional study, reported as a Letter to the Editor in the September 1, 2008 issue of the Journal of Acquired Immune Deficiency, investigators analyzed the risk of KS in patients switching from PIs to NNRTIs.

It total, 724 individuals were exposed to PIs and 604 were exposed to NNRTIs. Of these, 45 patients (42 gay men and 3 women) had current or past history of KS. Nearly half these patients (n = 21) were exposed for various reasons to NNRTIs after previously taking PIs, while the remaining 24 received PIs only. Of the total 55 KS cases recorded (1996 to date), 8 patients who discontinued treatment and 2 patients treated with triple nucleoside reverse transcriptase (NRTI) regimens were not included in the analysis.

Results

• There was no relapse or new case of KS in the 724 patients taking PIs.

• There were 7 cases of KS in the 604 patients on NNRTIs.

• 4 patients had their first expressions of KS after switching from PIs to NNRTIs, while 3 experienced relapse.

• Thus, in the overall population exposed to NNRTIs, the probability of a first KS tumor manifestation was 0.7% (4 of 604 patients).

• The rate of relapse among patients with a pre-existing KS history was 17.6% (3 of 17 patients).

• The probability of relapse was much higher than that of new expression of KS.

• Overall, KS was expressed within 25.7 (range 6 to 60) months.

"In agreement with previous case report studies," wrote the study authors, "relapse and any new expression of KS was found to be unrelated to immunologic or virologic failure of NNRTI-based HAART." [1,2]

PIs, they noted, "have direct anti-angiogenic, anti-KS, and antitumor effects." [3]

They concluded, "Withdrawal of PIs and switching to NNRTIs is a potentially major risk factor, especially on the grounds of past KS history, and should be carried out with caution."

9/19/08

Reference
VA Paparizos, KP Kyriakis, S Kourkounti, and others. The influence of a HAART regimen on the expression of HIV-associated Kaposi sarcoma [Letter to the Editor]. Journal of Acquired Immune Deficiency Syndromes 49(1): 111. September 1, 2008.

Other Citations

1. F Bani-Sadr, S Fournier, and JM Molina. Relapse of Kaposi's sarcoma in HIV-infected patients switching from a protease inhibitor to a non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy regimen. AIDS 17: 1580-1581. 2003.

2. AL Ridolfo, M Corbellino, N Tosca, and others. Is switching protease inhibitor-based effective antiretroviral therapy safe in patients with AIDS-associated Kaposi's sarcoma? AIDS 18: 1224-1226. 2004.

3. C Sgadari, G Barrilari, E Toschi, and others. HIV protease inhibitors are potent anti-angiogenic molecules and promote regression of Kaposi sarcoma. Nature Medicine 8: 225-232. 2002.