Efficacy and Impact on Lipids of Reduced Lopinavir/ritonavir Dosing

Lopinavir/ritonavir (Kaletra) effectively suppresses HIV, but can cause elevated blood lipid levels.

Because several sets of treatment guidelines recommend a target lopinavir plasma concentration (Cmin) above 3000 ng/mL in treatment-naive patients, French researchers investigated the virological efficacy and impact on tolerability of reducing the lopinavir/ritonavir dose to 2 tablets twice daily.

This prospective study enrolled 35 participants with a mean age of about 45 years; 28 were followed through Week 48. Before dose reduction, patients had been treated with regimens containing lopinavir/ritonavir for at least 6 months, had plasma HIV viral loads below 50 copies/mL for at least 3 months, and had lopinavir Cmin greater than 5000 ng/mL. Patients with a history of previous protease inhibitor failure or protease resistance mutations were not included.

At the time of dose reduction, the median viral load was 1.7 log copies/mL, the mean CD4 cell count was 346 cells/mm3, and the mean lopinavir Cmin was 7363 ng/mL.

Mean blood lipid levels (in mmol/L) were:

Total cholesterol: 5.4;
LDL cholesterol: 3.3.6;
HDL cholesterol: 1.46;
Triglycerides: 1.75.

Results

After reduction of lopinavir/ritonavir dosing, viral load remained below 50 copies in 23 of 28 subjects at Week 2 and Week 12; 27 at Week 24; and 25 at Week 36 and Week 48.

For all patients except one, detectable viral load values ranged between 55 and 682 copies/mL and were considered to be "blips."

Cmin (ng/mL) of LPV decreased after dose reduction:
- 4506 at Week 2;
- 4139 at Week 12;
- 3994 at Week 24;
- 4016 at Week 36;
- 4319 at Week 48.

All patients except one were maintained on the reduced dosing schedule throughout the study.

No significant variations in total cholesterol, LDL, HDL, or triglycerides were observed after dose reduction.

Only 2 patients complained of GI side effects during the study.

Conclusion

The researchers concluded, "A reduced dosing of lopinavir/ritonavir is associated with sustained virological response." However, lowered doses did not contribute to improved lipid profiles over 48 weeks.

Hosp. Saint-Antoine, Paris, France; Hosp. Tenon, Paris, France; Hosp. Pitie Salpetriere, Paris, France; Hosp. Avicenne, Paris, France.

10/03/06

Reference
J Meynard, K Lacombe, J Poirier, and others. Virological Efficacy and Impact on Lipids Profile of a Reduced Dosing (2 tablets BID) of Lopinavir/ritonavir (LPV/r) in HIV Infected Patients (Kaledose Trial). 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-1384.

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