AEGiS-Glasgow [PL2.1] Use of boosted protease inhibitors: pros and cons

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL2.1] Use of boosted protease inhibitors: pros and cons

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL2.1

Schlomo Staszewski
University of Frankfurt, Frankfurt, Germany

The introduction of newer, more potent PIs with more convenient dosing requirements, and the improvement in pharmacokinetic profiles achieved by ritonavir boosting may provide expanded options for HIV patients. Boosting two PIs simultaneously may have potential both with and without concomitant NRTIs.

Resistance and cross-resistance can limit the use of NRTIs in patients who have been treated with these agents for any length of time. Mitochondrial toxicity (lactic acidosis, myopathy, pancreatitis, peripheral neuropathy, lipodystrophy), associated with NRTIs, is a major rationale for NRTI-sparing therapy. In ART-experienced patients who have limited NRTI options due to resistance or toxicity, boosted double PI regimens could achieve sufficient viral suppression without the addition of other drug classes.

The combination of several PIs requires a detailed pharmacokinetic evaluation as different PIs also interact among themselves. Plasma concentrations may be favorable, or decreased fostering virologic failure, or highly increased causing toxicity.

Data regarding boosted double PI-only regimens in ART -naïve and -experienced patients have only been reported from observational cohort studies rather than from controlled randomized trials. These studies, performed mainly with heavily ART-experienced patients, demonstrated substantial reductions in viral load, increases in CD4 counts and reduced incidences of lipoatrophy. However, PI-related toxicities were common reasons for discontinuation. Patients with prior, extensive PI-resistant virus did not fare as well. This suggests that a double-boosted PI regimen is an effective salvage therapy in specific situations. The association between higher number of PI mutations and reduced likelihood of response suggests that the optimal indication for the use of such a regimen would be in patients with virologic failure of prior PI-sparing regimens, who may have reduced RTI options but retain PI-susceptible virus or in patients with low to moderate PI resistance. In contrast, patients with late-stage failure and extensive PI resistance should probably receive double-boosted PIs plus enfuvirtide and other active agents if available.

SESSION 2: TREATMENT STRATEGIES AND ORAL PAPERS

2004-11-14
PL2.1

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