Back HIV Treatment Approved HIV Drugs CROI 2008: Boosted Atazanavir (Reyataz) and Lopinavir/ritonavir (Kaletra) Have Similar Efficacy, but Different Side Effects: CASTLE

CROI 2008: Boosted Atazanavir (Reyataz) and Lopinavir/ritonavir (Kaletra) Have Similar Efficacy, but Different Side Effects: CASTLE

As antiretroviral therapy had improved, there are now multiple drug regimens that can produce full HIV suppression. However other factors -- including immediate side effects, long-term toxicities, and convenience -- may vary considerably. At the 15th Conference on Retroviruses and Opportunistic Infections this week in Boston, researchers reported data from the CASTLE trial, which compared 2 of the most widely used protease inhibitors, ritonavir-boosted atazanavir (Reyataz) and lopinavir/ritonavir (Kaletra), in treatment-naive participants. 

Past studies have shown that the drugs are similarly effective in treatment-experienced patients; atazanavir produces less blood lipid elevation, but often causes increased bilirubin.

CASTLE is an ongoing randomized, open-label, 96-week study assessing non-inferiority of 300/100 mg once-daily atazanavir/ritonavir versus 400/100 mg twice-daily lopinavir/ritonavir, both in combination with fixed-dose tenofovir plus emtricitabine (Truvada). The non-inferiority threshold was 10%.

A total of 883 treatment-naive patients were randomized and 878 were treated. Baseline demographics and characteristics were similar in both treatment arms. About 70% were men, the median age was 35 years, and 13% had hepatitis B or C coinfection. Median CD4 count was just over 200 cells/mm3 and median plasma HIV RNA was about 5 log10 copies/mL.

The primary study endpoint was the proportion of patients with HIV RNA < 50 copies/mL at week 48. Planned secondary assessments included percentage with HIV RNA < 400 copies/mL, CD4 cell count change, and safety parameters.


Result

Baseline HIV RNA < 100,000 copies/mL: 82% vs 81%, respectively;
In the subset of patients with < 50 cells/mm3 at baseline, 78% and 63%, respectively, achieved HIV RNA < 50 copies/mL.
At week 48, the mean CD4 count increases from baseline were 203 cells/mm3 in the atazanavir/ritonavir arm and 219 cells/mm3 in the lopinavir/ritonavir arm.
26% and 30%, respectively, experienced moderate-to-severe (Grade 2-4) adverse events:

Nausea: 4% vs 8%;
Rash: 3% vs 2%.

Bilirubin > 2.5 x upper limit of normal (ULN): 34% vs <1%;
Elevated total cholesterol > 240 mg/dL: 7% vs 18%;
Elevated glucose > 251 mg/dL: <1% in both arms.

Total cholesterol: 12% vs 24%
HDL ("good") cholesterol: 27% vs 32%;
Triglycerides: 13% vs 51%.

Fewer patients on atazanavir/ritonavir (2%) compared with lopinavir/ritonavir (7%) started lipid-lowering therapy.

Conclusion

"In treatment-naive patients, atazanavir/ritonavir demonstrated similar efficacy, a lower incidence of gastrointestinal-related adverse events, and a significantly better lipid profile (total cholesterol, triglycerides, non-HDL) compared to lopinavir/ritonavir," the investigators concluded.

"In combination with tenofovir and [emtricitabine], both atazanavir/ritonavir and lopinavir/ritonavir were well tolerated with few discontinuations through 48 weeks," they added. Once-daily atzanavir/ritonavir is an appropriate therapeutic option for treatment-naive patients."

Hosp St Louis, Paris, France; Hosp Civil de Guadalajara, Mexico; Hosp Natl Cayetano Heredia, Lima, Peru; Khonkaen Univ, Thailand; Hosp Intl Gral de Agudos Oscar Alende, Buenos Aires, Argentina; Brooklyn Med Ctr, Western Cape, South Africa; and Bristol-Myers Squibb R&D, Wallingford, CT.

2/5/08

Reference

J-M Molina, J Andrade-Villanueva, J Echevarria, and others.Efficacy and Safety of Once-daily Atazanavir/Ritonavir Compared to Twice-daily Lopinavir/Ritonavir, Each in Combination with Tenofovir and Emtricitabinein ARV-naive HIV-1-infected Subjects: The CASTLE Study, 48-week Results. CROI 2008. Boston. February 3-6, 2008.