August 17, 2006
Treatment with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-sparing regimens garnered quite a bit of interest several years ago, largely due to the toxicities of the NRTIs that were in wide use at the time, in particular stavudine (d4T, Zerit). In addition, some patients have extensive NRTI resistance, and it is unclear to what degree the NRTIs provide additional antiviral activity. The use of double-boosted protease inhibitors (PIs), usually without NRTIs, therefore had some appeal. The study1 presented by Staszewski et al at the XVI International AIDS Conference describes the experience with lopinavir/ritonavir (LPV/r, Kaletra) + saquinavir (SQV, Fortovase, Invirase) in treatment-experienced patients.
One hundred twenty-eight patients are included in this analysis. All were experiencing virologic failure due to drug resistance or toxicity or both. The median HIV RNA was 5.1 log, the median CD4+ cell count was 172 and the mean number of years of prior therapy was 6.3. Seventy-six of the patients underwent a treatment interruption until the medication-related toxicity resolved or until there was an apparent clearance of genotypic resistance. All received standard dose lopinavir/ritonavir plus 1,000 mg twice daily saquinavir.
At the end of 48 weeks, 78/128 (61%) patients remained on lopinavir/ritonavir + saquinavir and had undetectable HIV-RNA levels. Fifty patients out of 128 discontinued treatment before week 48, with 16 experiencing virologic failure. The mean CD4+ cell count change from baseline was 118 cells/mm3. In a multivariate analysis evaluating possible predictors of treatment success, only a higher CD4+ cell count and exposure to fewer drugs independently predicted virologic suppression.
This study provides some descriptive data on the use of a popular dual-boosted PI regimen containing lopinavir/ritonavir + saquinavir. The current, improved formulations of both drugs make this a much more attractive regimen than when only lopinavir/ritonavir soft-gel capsules and 200 mg saquinavir were available. However, it has not yet been proven that two boosted PIs are necessarily better than one, and notably absent here is the baseline degree of PI resistance. As shown in the several lopinavir/ritonavir monotherapy studies presented at this meeting, it is likely that a significant proportion of patients can be treated with this agent alone, albeit likely not to the same degree of success as with triple therapy. The role of double-boosted PIs therefore remains unclear.
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