Antiretroviral drug guidelines for the treatment of HIV infection: should protease inhibitors always be included in the initial regimen or not?

Combination antiretroviral therapy, usually consisting of 2 nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor (PI), has revolutionised the management of patients with HIV infection. PI-containing combinations are significantly superior to combinations of 2 nucleoside analogues, and the latter combination is now indicated only in very exceptional circumstances. However, long term adherence to complex regimens of antiretroviral drugs, and the emerging longer term toxicity associated with PIs and to a lesser extent, problems with long term adherence to complex regimens of antiretroviral drugs, make the use of 'protease-sparing' regimens attractive. Although in some cases such regimens may be associated with a lower chance of sustained suppression of viral load, leading to the development of drug resistance and virological rebound, they allow the preservation of a whole class of antiretrovirals for later use, avoid the risk of PI toxicity, and their use can also help to avoid important drug interactions associated with PIs.