Dual boosted PIs in salvage therapy

Several studies reported results from dual boosted PIs in salvage setting that included additional background nucleosides.

Lopinavir/r with amprenavir requires additional ritonavir boosting

In France, Raguin and colleagues presented 48 week results of the PUZZLE 1 study (ANRS 104) which looked at an additional 200mg/day ritonavir added to different combinations that included lopinavir/r and amprenavir (with NRTIs) in heavily experienced patients on current failing therapy. [5] While the resistance profile of these two drugs make the combination of interest, both lopinavir and amprenavir levels drop when used together.

Thirty-seven of 40 patients started treatment with median baseline viral load and CD4 of 4.7 log and 207 cells/mm3 respectively. Baseline resistance profile (all median) included seven PI mutations and a phenotypic resistance index of 9.7 for LPV and 2.6 for APV. Average number of antiretrovirals taken prior to randomisation was 7.7.

Twenty-six-week data presented at last year’s ICAAC showed that the additional ritonavir produced viral load reductions of –2.5 compared to –1.4 without. Twice as many patients achieved viral load < 50 copies/ml (62% versus 32%). This difference continued to remain significant for the additional ritonavir group with median viral load reduction at week 52 of –2.0 log compared to –1.1 (p=0.05). Undetectable viral load <50 copies was achieved by 39% (7/18) compared to 11% (2/18) in the two groups respectively (P=0.12).

Discontinuation of at least one of the two PIs (APV or LPV) occurred in six and eight patients and grade IV adverse events occurred in seven and 10 patients, respectively.


Raguin G, Chene G, Morand-Joubert L et al. Salvage therapy with lopinavir/r (LPV/r), amprenavir (APV) ± an additional boost with ritonavir (RTV): 1-year results of PUZZLE-1 – ANRS 104 study. 2nd IAS Conference on HIV Pathogenesis and Treatment, 13-16 July 2003, Paris. Abstract 585.

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