Background: Cobicistat, which has no antiretroviral activity, enhances the pharmacokinetics of ATV as effectively as ritonavir in healthy volunteers and HIV-infected adults. Efficacy and safety outcomes of this Phase 3, randomized, double-blind, active-controlled trial in HIV-1-infected treatment na´ve adults (GS-US-216-0114/NCT01108510) were previously presented; ATV+c was non-inferior to ATV+r, áboth in combination with FTC/TDF, at Weeks 48 and 144, and both regimens achieved high rates of virologic success with comparable safety and tolerability. Here we describe virologic response and treatment discontinuation by subgroups not previously presented (race, gender, age, as well as baseline CD4 count and HIV RNA).
Methods: Subgroup analyses by baseline CD4 category (≤200, 201-350, >350 cells/mm3), baseline viral load (VL ≤100,000, >100,000 c/mL), race, sex and age category (<40, ≥40 years) evaluated virologic success (VL <50 c/mL, ITT-FDA snapshot algorithm) and discontinuation due to adverse events (AEs) at Week 48.
Results: Of 692 patients randomized, 344 received ATV+c and 348 ATV+r. Virologic success: in patients with baseline CD4 count ≤200 cells/mm3, 88.3% and 87.7%, respectively; in patients with baseline VL >100,000 c/mL, 86.4% and 86.0%; in White patients, 85.4% and 88.8%; in Black/African American patients, 73.8% and 82.5%; in Asian patients, 97.7% and 86.5%; in patients aged <40 years, 80.9% and 85.9%; in patients aged ≥40 years, 91.9% and 89.5%; in male patients, 85.0% and 89.2%; and in female patients, 86.0% and 78.7%. There were no significant differences in ATV+c vs. ATV+r odds ratios for virologic success (Figure 1) overall or by subgroup. Discontinuation due to AEs occurred in 7.3% and 7.2%, respectively, and did not significantly differ by regimen within each subgroup (Figure 2).
Conclusion: Virologic success rates were high and similar between ATV+c and ATV+r regardless of race, sex and age, as well as in patients with baseline CD4 count ≤200 cells/mm3 or baseline VL >100,000 c/mL. Discontinuation due to AEs was uncommon regardless of subgroup and was similar between regimens. These findings support the combination of either ATV+c or ATV+r with FTC/TDF as effective treatment options for HIV-infected patients. A fixed dose combination tablet of ATV/c received FDA approval on 01/29/2015.
Gilead, Janssen, ViiV:
Achillion, BI, BMS, Gilead, GSK, Hoffman, LaRoche, Idenix, Janssen, Merck, Novelos, Pfizer, Sangamo, Serono, Taimed, Tobira, Vertex: Investigator , Research support
Gilead, Janssen: Speaker's Bureau , Speaker honorarium
Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merk & Co., ViiV Healthcare: Scientific Advisor , Consulting fee
P. Shalit, Gliead Sciences, GlaxoSmithKline, Janssen: Investigator , Research support
Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck: Consultant , Consulting fee
Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, ViiV: Speaker's Bureau , Speaker honorarium
H. Cao, Gilead Sciences, Inc.: Employee , Salary
Y. P. Liu, Gilead Sciences: Employee and Shareholder , Salary
J. Myers, Bristol-Myers Squib: Employee and Shareholder , Salary
L. Rosenblatt, Bristol-Myers Squibb: Employee and Shareholder , Salary
L. Yang, Bristol-Myers Squibb: Employee and Shareholder , Salary
J. Szwarcberg, Gilead Sciences: Employee , Salary