Atazanavir Plus Ritonavir or Saquinavir Compared to Lopinavir/Ritonavir in Patients Experiencing Multiple Virological Failures

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The objective of the current study was to evaluate atazanavir (Reyataz)/ritonavir (Norvir) (ATV/RTV) (300/100 mg) once daily, atazanavir/saquinavir (Invirase) (ATV/SQV) (400/1200 mg) once daily, and lopinavir/ritonavir (Kaletra) (LPV/RTV) (400/100 mg) twice daily, each with tenofovir (300 mg) once daily and a nucleoside reverse transcriptase inhibitor (NRTI) in treatment-experienced HIV-infected patients.

This was a randomized, open-label, 48-week multicenter trial of 358 randomized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA >= 1000 copies/ml and CD4 cell count >= 50 x 106 cells/l.

Results

· The primary efficacy endpoint [plasma HIV RNA reduction assessed by time-averaged difference (TAD)] was similar for ATV/RTV and LPV/RTV [TAD 0.13] at 48 weeks;

· Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml, respectively;

· Mean CD4 cell count increases were 110 and 121 x 106 cells/l for ATV/RTV, and LPV/RTV, respectively;

· The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters;

· Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV (P <= 0.005);

· Lipids in the LPV/RTV arm at week 48 generally increased from baseline;

· Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms (P < 0.05 versus ATV/RTV), as were anti-diarrheal agents (P <= 0.04 versus both ATV treatments);

· No new or unique safety findings emerged.

Conclusions

In conclusion, the authors write, “ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids. Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients.”

Discussion

In summary, atazanavir boosted with ritonavir once daily is as effective in treatment-experienced patients as a currently accepted standard of care (lopinavir/ritonavir twice daily). The increased exposure to atazanavir associated with ritonavir boosting was safe and well tolerated, with no unexpected or late-emerging adverse events.

Furthermore, atazanavir boosted with ritonavir was not associated with adverse lipid effects observed with ritonavir and other PI, and its use resulted in a reduced need for both concomitant lipid-lowering and antidiarrheal medications.

Given the fact that atazanavir boosted with ritonavir is effective when administered once daily, its use may decrease pill burden, promote adherence and enhance long-term treatment success.

Atazanavir boosted with ritonavir once daily is an effective and tolerable option for antiretroviral therapy-experienced patients with HIV infection, according to the authors.

04/11/05

Reference
M Johnson and others. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 19(7):685-694. April 29, 2005.