Boosted protease inhibitor monotherapy in HIV-infected adults: outputs from a pan-European expert panel meeting

Abstract

While the introduction of combination highly active antiretroviral therapy (HAART) regimens represents an important advance in the management of human immunodeficiency virus (HIV)-infected patients, tolerability can be an issue and the use of several different agents may produce problems. The switch of combination HAART to ritonavir-boosted protease inhibitor (PI) monotherapy may offer the opportunity to maintain antiviral efficacy while reducing treatment complexity and the risks of toxicity. Current European AIDS Clinical Society (EACS) guidelines recognise ritonavir-boosted PI monotherapy with twice-daily lopinavir/ritonavir or once-daily darunavir/ritonavir as a possible option in patients who have intolerance to nucleoside reverse transcriptase inhibitors, or for treatment simplification. Clinical trials data for PI boosted monotherapy are encouraging, showing substantial efficacy in the majority of patients; however, further data are required before this approach can be recommended as a routine treatment. Available data indicate that the most suitable candidates for the use of boosted PI monotherapy are long-term virologically suppressed patients who have demonstrated good adherence to antiretroviral therapy, who do not have chronic hepatitis B, have no history of treatment failure on PIs and are able to tolerate low-dose ritonavir.

Figure 1

a) Proportion of patients remaining on original treatment regimen 1 year after initiating HAART; b) Reasons for discontinuing HAART between 2002–2004 [1].

Figure 2

Efficacy of a) Lopinavir/r [21]and b) Darunavir/r monotherapy vs comparator arms [7,20]. Efficacy was assessed in the ITT population and modification of treatment was considered failure in the MONET and MONOI darunavir/r monotherapy trials [7,20]. In the lopinavir/r monotherapy trials [21], there was some variance in what was considered failure. In OK04 2005, treatment modification = failure. In OK04 2008, treatment modification ≠ failure. In KALMO failure was defined as confirmed HIV-1 RNA > 1,000 copies/mL. In MO6-613 non-responders were defined as those who either did not complete 96 weeks of treatment, had HIV-1 RNA at > 50 copies/mL at week 96, or experienced confirmed virological rebound before week 96.

Figure 3

a) Abbott 613 trial: Changes in limb fat over time [30]b) MONOI: Median change in limb fat from baseline to week 48 [31].