July 8, 2003
In the mid-to-late 1990s, protease inhibitors (PIs) became widely available in high-income countries. When used as part of combination therapy, PIs helped put KS into remission. Researchers suspected that this occurred because PI combination therapy raised CD4+ cell counts and reduced levels of HIV in the blood. The changes in cell counts and viral load allowed the immune system a chance to begin repairing itself and perhaps to better fight KS tumours.
However, this theory may now have to be reexamined, based on new findings from Paris, France. There, doctors reported that five PHAs who switched from a PI-based regimen to a regimen based on non-nukes (NNRTIs), such as efavirenz (Sustiva, Stocrin) or nevirapine (Viramune), had relapses in their KS.
On average, the KS relapsed one year after the PHAs switched from PIs to a non-nuke. At the time the relapse occurred, in four of the five PHAs, CD4+ cell counts were relatively high -- ranging between 350 and 1,300 cells. Also, in four of the five PHAs, viral loads were low -- fewer than 20 copies.
The doctors note that the recurrence of KS in their patients cannot be explained by low CD4+ counts or high viral loads. In seeking other explanations, the doctors report certain results of test-tube and animal experiments done by researchers. In these experiments, PIs seem to prevent the growth and development of KS tumours. The drugs appear to do this by blocking the production of growth factors (chemical messengers) needed by KS cells. Moreover, exposure to PIs caused KS cells to die.
The report by the French doctors about KS relapse is interesting. However, much more study and analysis is needed to confirm these findings in other PHAs as well as to reconcile them with results from other clinical trials where combination therapy with either PIs or NNRTIs resulted in the regression of KS.
In the meantime, the French doctors warn that other doctors should use caution when switching their patients who previously had KS from a PI to an NNRTI.
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