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. Boosted protease inhibitor monotherapy is one of the appealing options being investigated. Herein we review uncontrolled and controlled clinical trials evaluating boosted protease inhibitor monotherapy in several clinical settings: maintenance therapy, induction-maintenance strategies, and first-line treatment. Boosted lopinavir monotherapy has been largely investigated in maintenance and induction-maintenance strategies, showing its ability to maintain viral suppression in the majority of participants. The major 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-associated resistance mutation was detected in patients who failed on boosted lopinavir monotherapy. Three uncontrolled maintenance strategy studies with boosted atazanavir monotherapy showed conflicting results. Thus, the reassuring results obtained with lopinavir might not be extended to the whole protease inhibitor 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 triple combination showed that the latter outperformed the boosted protease inhibitor monotherapy in this clinical setting. In summary, a boosted protease inhibitor single-agent strategy can maintain continuous plasma HIV-RNA suppression in a large proportion of patients already suppressed on a standard triple combination. The more frequent occurrence of low-level viremia, however, does not allow the widespread use of such a strategy outside of clinical studies at this time.
Sahali
Sabrinel
S
AP-HP, Bicêtre University Hospital, Department of Internal Medicine and Infectious Diseases, Paris-Sud University, Le Kremlin-Bicêtre, France.
Chaix
Marie-Laure
ML
Delfraissy
Jean-François
JF
Ghosn
Jade
J
D019380:Anti-HIV Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004357:Drug Synergism; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D019438:Ritonavir / Q000009:adverse effects / Q000494:pharmacology*; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019438:Ritonavir