Clumeck N, Brun S, Sylte J, Isaacson J, Chen S, Lazzarin A, Girard PM, Rockstroh J, Becker S, Telenti A, Bergmann F, Danner S, Ho D, Tubiana R, Carosi G, Bertz R, Hsu A, King M, Kempf D, Sun E; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 201 (abstract no. 525).

CHU Saint-Pierre-Brussels.

Background: Kaletra is a novel HIV protease inhibitor (PI) with mean trough concentrations that exceed its protein binding corrected EC50 for 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 log10 c/mL. The median number of prior PIs was 3. Sixty-eight percent of baseline viruses demonstrated > or = 4-fold loss in susceptibility to > or = 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.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-HIV Agents
• HIV
• HIV Infections
• HIV Protease Inhibitors
• Humans
• Oxazines
• Pyrimidinones
• Safety
• Viral Load
• efavirenz
• lopinavir
• methods

Other ID:

• GWAIDS0006812

UI: 102244308

From Meeting Abstracts