Ritonavir-boosted Elvitegravir Has Potent and Durable Activity in Treatment-experienced Patients with Active Optimized Background Therapy

By Ronald Baker, PhD

Integrase inhibitors are a new class of antiretroviral agents that have shown promise as potent and safe drugs in the treatment of HIV infection. Elvitegravir is an experimental integrase inhibitor from Gilead Sciences.

This new drug works best against HIV when patients use it in combination with the injectible entry inhibitor enfuvirtide (T-20; Fuzeon) and other active drugs, including ritonavir-boosted protease inhibitors, according to the results of a study presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago (September 17-20, 2007).

This ongoing randomized and partially-blinded Phase 2 study demonstrated that treatment-experienced HIV patients given 125 mg once-daily elvitegravir boosted with ritonavir had a superior average change in HIV RNA at Week 24 (DAVG24) versus a boosted comparator protease inhibitor (CPI) arm (Zolopa and others, CROI 2007).

A new analysis of the data, presented at ICAAC, revealed more detail concerning resistance and the influence on outcomes of optimized background therapy (OBT).

Subjects received NRTIs +/- T-20 with either a boosted comparator PI or boosted elvitegravir 20, 50, or 125 mg. PIs were permitted after Week 8. Patients in the 125 mg elvitegravir/ritonavir arm were analyzed for their viral load responses by activity of the OBT.

Results

• At baseline, 125 mg elvitegravir/ritonavir patients (n=73) had a median HIV RNA of 4.9 log10 copies/mL, 11 PI resistance mutations, and 3 thymidine analog mutations.

• Excluding data after adding a PI, subjects (n=26) with no active agents in their OBT had a mean change from baseline in HIV RNA of -0.7 log10 copies/mL at Week 24 compared to -1.7 log10 copies/mL (p=0.027) for subjects (n=28) with ?1 active NRTI and -2.9 log10 copies/mL (p<0.0001) for subjects (n=19) with first use of T-20.

• The DAVG24 for elvitegravir/ritonavir 125 mg subjects with newly added T-20 (n=19) was -2.6 log10 copies/mL compared to -1.6 log10 copies/mL for boosted CPI subjects with newly added T-20 (n=12; p=0.03).

• Only 2 elvitegravir/ritonavir 125 mg patients added a PI prior to Week 16; at Week 16, 74% (14/19) elvitegravir/ritonavir 125 mg subjects with new T-20 had HIV RNA <50 copies/mL compared to 25% (3/12) boosted CPI subjects with new T-20 (ITT, M=F; p=0.012).

• Elvitegravir/ritonavir 125 mg subjects who added a PI (n=23) had an additional mean change in HIV RNA of -1.1 log10 copies/mL over a median of >16 weeks after adding a PI.

Conclusion

Based on these results, the study authors concluded, "Significant, durable viral suppression by elvitegravir/ritonavir 125 mg occurred in subjects with ?1 active drug in OBT without boosted PIs."

Further, they stated, "Regimens with elvitegravir/ritonavir 125 mg and OBT including boosted PIs from the outset could have even greater antiviral activity and are planned for study."

Stanford Univ., Stanford, CA, UCSF/San Francisco VAMC, San Francisco, CA, Circle Med., Norwalk, CT, CSI Clinical Trials, Fountain Valley, CA, Gilead Scences, Foster City, CA.

09/25/07

Reference
AR Zolopa, H Lampiris, G Blick, and others. The HIV Integrase Inhibitor Elvitegravir (EVG/r) has Potent and Durable Activity in Treatment-Experienced Patients with Active Optimized Background Therapy (OBT). 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. September 17-20, 2007. Chicago, IL. Abstract (oral) H-714.