High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response

• Published in: HIV clinical trials Vol. 8; no. 4; p. 193
• Main Authors: Podzamczer, Daniel, King, Martin S, Klein, Cheri E, Flexner, Charles, Katlama, Christine, Havlir, Diane V, Letendre, Scott L, Eron, Joseph J, Brun, Scott C, Bernstein, Barry
• Format: Journal Article
• Language: English
• Published: England 01.07.2007
• Subjects: Adult; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Resistance, Viral; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - pharmacokinetics; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; HIV-1 - physiology; Humans; Lopinavir; Male; Middle Aged; Pyrimidinones - administration & dosage; Pyrimidinones - pharmacokinetics; Pyrimidinones - therapeutic use; Ritonavir - administration & dosage; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; RNA, Viral - analysis; Viral Load
• ISSN: 1528-4336
• DOI: 10.1310/hct0804-193

To investigate the efficacy and safety of high-dose lopinavir/ritonavir (LPV/r) therapy in multiple protease inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced subjects. Thirty-six HIV-1-infected subjects were randomized to LPV/r 400/300 mg or 667/167 mg bid in a 48-week, open-label study. Subjects also received investigator-selected nucleoside reverse transcriptase inhibitors (NRTIs). Primary outcomes were the proportion of subjects with HIV-1 RNA levels <50 copies/mL at week 24 and time until loss of virologic response through week 48. Six of 17 (35%) and 10 of 19 (53%) subjects in the 400/300 and 667/167 groups, respectively, completed 48 weeks of treatment. Median durations of follow-up in discontinued subjects and all subjects were 15 weeks and 32 weeks, respectively. Forty-four percent of subjects achieved HIV-1 RNA <50 copies/mL at least once; 18% (400/300 mg) and 21% (667/167 mg) of subjects achieved HIV-1 RNA <50 copies/mL at week 24 (intent-to-treat analysis). Corresponding results at week 48 were 18% (400/300 mg) and 26% (667/167 mg). No statistically significant differences in adverse event incidence occurred between treatment groups, except for a higher vomiting rate in the 400/300 mg dose group. Predictors of response included baseline LPV inhibitory quotient and number of active NRTIs. Higher doses of LPV/r may provide substantial antiviral activity in multiple class-experienced subjects.