High-dose Lopinavir/Ritonavir (Kaletra) Significantly Improves Response to Therapy without Increasing Adverse Events in Highly Treatment-experienced HIV Patients

By Ronald Baker, PhD

Higher-dose lopinavir/ritonavir (Kaletra) substantially enhances anti-HIV activity in multiple drug class-experienced patients, according to results of a study published in the July/August 2007 issue of HIV Clinical Trials.

Researchers at the Hospital Universitari de Bellvitge in Barcelona, Spain and Abbott Laboratories evaluated the efficacy and safety of lopinavir/ritonavir 667/167 mg vs the standard dose of 400/300 mg, both twice-daily, in a 48-week randomized, open-label study of 36 highly treatment-experienced HIV patients. Study participants also received standard doses of nucleoside reverse transcriptase inhibitors (NRTIs) chosen by the investigators.

There were 2 primary outcome measures:

(1)	proportion of patients experiencing HIV RNA levels <50 copies/mL at 24 weeks;
(2)	time to loss of virological response through week 48.

Results

• Of 326 patients enrolled, 6 of 17 (35%) in the 400/300 mg group and and 10 of 19 (53%) in the 667/167 mg group completed 48 weeks of treatment.

• Median durations of follow-up for discontinued subjects and for all subjects were 15 weeks and 32 weeks, respectively.

• 44% of patients achieved HIV RNA <50 copies/mL at least once.

• Intent-to-treat analysis (missing=failure) showed that 18% of patients receiving lopinavir/ritonavir 400/300 mg and 21% receiving lopinavir/ritonavir 667/167 mg achieved HIV RNA <50 copies/mL at week 24.

• At week 48, 18% of patients receiving 400/300 mg and 26% receiving 667/167 mg achieved HIV RNA <50 copies/mL.

• Predictors of response included baseline lopinavir inhibitory quotient and number of active NRTIs.

• There were no statistically significant differences in the incidence of adverse events between the 2 treatment groups, except for a higher frequency of vomiting in the 400/300 mg dose group.

Conclusion

Based on these findings, the study authors concluded, "Higher doses of lopinavir/ritonavir may provide substantial antiviral activity in multiple class-experienced subjects."

Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain.

08/31/07

Reference
D Podzamczer, M S King, C E Klein, and others. High-Dose Lopinavir/Ritonavir in Highly Treatment-Experienced HIV-1 Patients: Efficacy, Safety, and Predictors of Response. HIV Clinical Trials 8(4): 193-204. July/August 2007.