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Protease inhibitors: no knockout blow, but could be the best punch yet.


 Researchers are calling the two recently approved protease inhibitors the best news in AIDS treatment since AZT, but are cautioning against unrealistic expectations. Nucleoside analogue monotherapy reduces viral load 3-fold, nucleosides in combination therapy reduce viral load 10-fold, and protease inhibitors drop viral load by 1000-fold. When protease inhibitors are taken in combination with nucleoside analogues, HIV has been reduced to below detectable levels for more than six months. These results have some doctors speculating about total suppression of HIV replication. Triple combinations are superior, with no added toxicity. Protease inhibitors, however, have problems with resistance, some of which are overcome through increased dosages. Resistance to one protease inhibitor can cross over to another, and researchers have found that some HIV-positive patients in Los Angeles already have viral strains resistant to protease inhibitors, even though they have never been treated with them. Resistance can be delayed by avoiding monotherapy, complying with the prescribed treatment, and by using high dosages. Long-term safety of protease inhibitors has not yet been determined.
