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Safety, tolerability and efficacy of darunavir/ritonavir in treatment-experienced women with HIV infection: 24-week interim analysis of GRACE (Gender, Race, And Clinical Experience)
Presented by Judith Currier, United States.
J. Currier1, K. Squires2, D. Averitt Bridge3, R. Ryan4, J. Mrus5, A. Tennenberg5, R. Falcon5, on behalf of the GRACE Study Group
1University of California, Los Angeles, School of Medicine, Los Angeles, United States, 2Jefferson Medical College of Thomas Jefferson University, Philadelphia, United States, 3The Well Project, Inc., Atlanta, United States, 4Tibotec, Inc., Yardley, United States, 5Tibotec Therapeutics, Bridgewater, United States
Background: GRACE is a multi-center, open-label phase IIIb trial designed to assess sex and race differences in efficacy, safety, and tolerability of darunavir/ritonavir over 48 weeks in treatment-experienced patients. The study was designed to enroll a predominantly female, racially diverse population, and the 65 GRACE study sites in North America were selected to meet these objectives. We report a pre-planned interim analysis of the first 203 patients (of a total of 429 enrolled) to complete Week 24 or discontinue sooner.
Methods: Inclusion criteria included adults with prior antiretroviral treatment and HIV-RNA ³1000 copies/mL. All patients received darunavir/ritonavir 600/100mg bid plus optimized background regimen. Commercially available NRTIs and NNRTIs, including etravirine (TMC125), were allowed. This pre-planned interim analysis was conducted primarily to assess safety and tolerability. We present preliminary efficacy results using ITT-TLOVR and TLOVR-non-virologic failure (non-VF) algorithms; the latter excludes patients who discontinued for reasons other than VF.
Results:
| | Women
(n=180) | All patients
(n=203) | Baseline demographics and disease characteristics
Age, mean (range), years
Race/ethnicity, n (%)
African American
Hispanic/Latino
Caucasian
Other
Viral load, mean (SD), log10 copies/mL
CD4 count, median (range), cells/mm3
Treatment history and baseline resistance
Prior use of ³2 PIs, n (%)
³3 IAS-USA primary PI mutationsa at BL, n (%)
Active ARVs in OBRb, n (%c)
0
1
³2
Discontinuations, n (%)
AEs, n (%)
Lost to follow-up
Non-compliant
Withdrew consent
Virologic failure
Other |
42 (19-78)
117 (65.0)
40 (22.2)
21 (11.7)
2 (1.1)
4.67 (0.86)
206 (1-868)
107 (59.5)
20 of 177 (11.3)
29 (16.8)
45 (26.0)
99 (57.2)
44 (24.4)
14 (7.8)
11 (6.1)
5 (2.8)
5 (2.8)
1 (0.6)
8 (4.4)
|
42 (19-78)
130 (64.0)
43 (21.2)
27 (13.3)
3 (1.5 )
4.69 (0.86)
202 (1-868)
122 (60.1)
27 of 200 (13.5)
37 (19.1)
48 (24.7)
109 (56.2)
46 (22.7)
15 (7.4)
11 (5.4)
6 (3.0)
5 (2.5)
1 (0.5)
8 (3.9)
| Response rates
Confirmed viral load <50 copies/mL, n (%) [ITT-TLOVR]
Confirmed viral load <50 copies/mL, n (%) [TLOVR-non-VF]
Increase in CD4 count from baseline, median (range), cells/mm3 [ITT-NC=F] |
91 50.6)
91 of 139 (65.5)
44 (-251-644)
|
103 (50.7)
103 of 159 (64.8)
47 (-251-644)
| | aAugust-September 2007 list; bDoes not include etravirine or DRV; cCalculation based on 173 women and 194 overall with baseline phenotypes; ITT, intention to treat; TLOVR, time to loss of virologic response; NC=F, non-completer=failure. |
Conclusions: No unexpected AEs were noted in this interim analysis. The discontinuation rate for reasons other than AEs for the first 203 patients was somewhat higher than expected. The GRACE study is fully enrolled (287 women, 142 men), demonstrating that women from North America can be successfully recruited to participate in clinical trials of antiretrovirals in HIV infection.
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