Paper # 58LB
Single-tablet, Fixed-dose Regimen of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Achieves a High Rate of Virologic Suppression and GS-9350 Is an Effective Booster
Calvin Cohen*1, D Shamblaw2, P Ruane3, R Elion4, E DeJesus5, H Liu6, L Zhong6, D Warren6, B Kearney6, and S Chuck6
1Community Res Initiative of New England, Boston, MA, US; 2San Diego, CA, US; 3Los Angeles, CA, US; 4Whitman Walker Clin, Washington, DC, US; 5Orlando Immunology Ctr, FL, US; and 6Gilead Sci, Foster City, CA, US
Background: Suppression of HIV RNA depends on
adherence to HAART, which is facilitated by a single-tablet regimen. GS-9350
boosts the integrase inhibitor elvitegravir (EVG). These agents and emtricitabine
(FTC)/tenofovir disoproxil fumarate (TDF) have been co-formulated into a
single-tablet regimen (Quad). In addition, GS-9350 boosts plasma levels of atazanavir
(ATV) equivalent to ritonavir (RTV).
Methods: Two ongoing, prospective, double-blind,
double-dummy, active controlled, Phase 2 studies in treatment-naďve subjects comparing
1) 2 once-daily, single-tablet regimens—Quad vs Efavirenz/FTC/TDF (Atripla),
and 2) FTC/TDF + ATV with GS-9350 150 mg vs RTV 100 mg. Eligible
subjects had plasma HIV RNA ≥5,000 copies/mL, CD4 cell counts ≥50
cells/mm3, and no resistance to NRTI, NNRTI, or PI, and were
randomized 2:1 (stratified by HIV RNA >100,000 copies/mL) to receive Quad or
Atripla in one study and GS-9350 or RTV in the second study. In both studies, the
primary endpoint was the proportions with HIV RNA <50 copies/mL at Week 24.
Results:
|
|
Study 236-0104
|
Study 216-0105
|
|
Quad
n=48
|
Atripla
n=23
|
GS-9350
n=50
|
RTV
n=29
|
|
Baseline Characteristics
Age, mean years
Male
Caucasian
HIV RNA, mean log10
copies/mL
CD4 cells/mm3,
mean
|
36
92%
69%
4.59
378
|
35
91%
78%
4.58
454
|
37
94%
62%
4.56
365
|
34
86%
55%
4.69
343
|
|
Discontinuations
Due to adverse event
(AE)
|
3
0
|
3
1
|
4
2
|
3
1
|
|
Week 24
HIV RNA < 50 copies/mL
(ITT, M=F)
HIV RNA < 50 copies/mL (ITT, M=E)
Increase in CD4
cells/mm3
AEs related to
randomized study drug
Grade 3 or 4 adverse
events
|
90%
96%
161
35%
0
|
83%
95%
113
57%
2
|
84%
91%
203
20%
2
|
86%
96%
199
24%
0
|
Conclusions: The efficacy of the Quad tablet met
criteria for non-inferiority to Atripla, and the Quad arm had a lower rate of study
drug-related AE than the Atripla arm. GS-9350-boosted ATV had similar efficacy and
safety to ritonavir-boosted ATV. GS-9350 is an effective booster of EVG and
ATV.
|
