Ritonavir-Boosted Protease Inhibitor Monotherapy for the Treatment of HIV-1 Infection

Guidelines for the use of antiretrovirals for HIV-1 infection recommend combining at least three agents.Toxicities, cost, and the complexity of such regimens warrant the search for other options. Boostedprotease inhibitor monotherapy is one of the appealing options being investigated. Herein we reviewuncontrolled and controlled clinical trials evaluating boosted protease inhibitor monotherapy in severalclinical settings: maintenance therapy, induction-maintenance strategies, and first-line treatment.Boosted lopinavir monotherapy has been largely investigated in maintenance and induction-maintenancestrategies, showing its ability to maintain viral suppression in the majority of participants. Themajor concern is the higher proportion of patients experiencing transient episodes of low-level viremia(HIV-RNA 50-500 copies/ml) when compared to classical triple regimens. No protease inhibitor-associatedresistance mutation was detected in patients who failed on boosted lopinavir monotherapy. Threeuncontrolled maintenance strategy studies with boosted atazanavir monotherapy showed conflictingresults. Thus, the reassuring results obtained with lopinavir might not be extended to the whole proteaseinhibitor class, warranting further studies with new generation protease inhibitors such as darunavir.Finally, one controlled trial comparing first-line boosted lopinavir monotherapy to a standard triplecombination showed that the latter outperformed the boosted protease inhibitor monotherapy in thisclinical setting. In summary, a boosted protease inhibitor single-agent strategy can maintain continuousplasma HIV-RNA suppression in a large proportion of patients already suppressed on a standard triplecombination. The more frequent occurrence of low-level viremia, however, does not allow the widespreaduse of such a strategy outside of clinical studies at this time.