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Background: Kaletra is a novel HIV protease inhibitor (PI) with mean trough concentrations that exceed its protein binding corrected EC50for wild-type HIV by more than 75-fold when dosed at 400/100 mg BID. This increased inhibitory quotient (IQ) should provide antiviral activity in patients who have developed resistance to other PIs.
Methods: Multiple-PI-experienced/NNRTI-naive patients (n = 57) with viral load (VL) >1000 c/mL on therapy were randomized to Kaletra at either 400/100 (3 capsules) or 533/133 mg (4 capsules) BID with EFV 600 mg QD and NRTIs. After 24 weeks, all patients began open-label 533/133 mg BID dosing.
Results: Median baseline (BL) viral load was 4.5 log10c/mL. The median number of prior PIs was 3. Sixty-eight percent of baseline viruses demonstrated>4-fold loss in susceptibility to>3 licensed PIs. Mean susceptibility (IC50) to ABT-378 at BL was 16-fold over wild type. At wk 48 by ITT M = F analysis, VL was <400 c/mL in 65% (OT: 80%) and <50 c/mL in 56% (OT: 70%). Observed response rates (<400 c/mL—dropouts as censored) for patients with <10-fold, 10- to 40-fold and >40-fold reduced baseline susceptibility to ABT-378 were 26/28 (93%), 11/15 (73%), and 2/7 (29%). Mean CD4 increase from BL to wk 48 was 94 cells/mL overall. The most common drug-related adverse events of at least moderate severity were diarrhea and asthenia. Lipid elevations were the most common laboratory abnormality. Four patients have discontinued for virologic failure; 5 patients have discontinued for adverse events to date (3 study drug-related); 1 patient has discontinued for personal reasons and another died.
Conclusion: Kaletra and EFV are well tolerated and exhibit durable antiretroviral effect in multiple-PI-experienced patients through 48 weeks of treatment.
Authors
1C.H.U. Saint-Pierre-Brussels;2Hosp. S. Raffaele;3Hop. Rothschild;4Med. Klin. der Univ. Bonn;5Pacific Horizons Med. Group;6Hop. de Beaumont;7Charite Humboldt-Univ. Berlin;8Academic Med. Ctr. Amsterdam;9Aaron Diamond AIDS Res. Ctr.;10Hop. Pitie-Salpetriere;11Univ. of Brescia; and12Abbott Labs.
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