August 17, 2006
This was a fairly large, clinic-based, retrospective analysis1 of virologic response rates to a broad range of ritonavir (RTV, Norvir)-boosted protease inhibitors (PIs), including saquinavir (SQV, Invirase) 1,000 mg twice daily, indinavir (IDV, Crixivan) 800 mg twice daily, lopinavir (LPV) 400 mg twice daily, amprenavir (APV, Agenerase) 600 mg twice daily, atazanavir (ATV, Reyataz) 300 mg once daily and tipranavir (TPV, Aptivus) 500 mg twice daily.
The virologic response rates (defined as a decrease in HIV plasma viral load exceeding 1.0 log10 copies/mL over 24 weeks) are summarized below, as a function of the number of PI resistance (PIR) mutations present at baseline.
|Virologic Response Rates to Ritonavir-Boosted PIs|
(< 5 PIR mutations)
(> 5 PIR mutations)
All the drugs were equally well tolerated, except for indinavir + ritonavir, which had quite a high rate of discontinuation due to toxicity (23%). This is a very good "snapshot" of the use of PIs in clinical practice in non-naive patients. It underscores the important role of resistance testing in this setting. If isolates have a limited number of mutations in the protease gene (as would be expected in patients with more extensive prior exposure to non-nucleoside reverse transcriptase inhibitors [NNRTIs] and more limited exposure to PIs), most available PIs would remain effective. However, with more advanced courses of therapy, efficacy is more modest, and the use of newer agents such as tipranavir + ritonavir seems to be favored.
The relatively preserved efficacy of saquinavir + ritonavir (an agent that has not been used extensively in recent years) is a bit surprising, but is worthy of note. It may be worth reconsidering its utility in salvage therapy, on its own or as part of double-PI regimens, for which it may be particularly well suited, based on pharmacokinetic parameters.
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