In an effort to reduce drug-related side-effects and make treatment more convenient, researchers have studied the use of single protease inhibitors as monotherapy. Monotherapy has a bad reputation, since single NRTIs did not control HIV over the long term due to the rapid development of drug resistance.

But some modern protease inhibitors used alone (except for a small boosting dose of ritonavir) seem to be able to keep HIV under control in some people, especially those with low viral loads. The drugs most often studied as monotherapy are lopinavir/ritonavir (Kaletra) and atazanavir (Reyataz). Monotherapy has been tried both as a first-line regimen and as part of an induction and maintenance strategy, whereby patients start with a traditional combination regimen and eliminate all but the boosted protease inhibitor once viral load is suppressed below 50 copies/ml.

For further discussion of protease inhibitor monotherapy, see Starting HIV Treatment.