The SPARTAN study: a pilot study to assess the safety and efficacy of an investigational NRTI- and RTV-sparing regimen of atazanavir (ATV) experimental dose of 300mg BID plus raltegravir (RAL) 400mg BID (ATV+RAL) in treatment-naïve HIV-infected subjects
M.J. Kozal1, S. Lupo2, E. DeJesus3, J.-M. Molina4, C. McDonald5, F. Raffi6, J. Benetucci7, M. Mancini8, R. Yang8, V. Wirtz8, L. Percival8, J. Zhang8, A. Farajallah8, B.-Y. Nguyen9, R. Leavitt9, D. McGrath8, M. Lataillade8, for the SPARTAN study team
1Yale University School of Medicine and VA CT Healthcare System, New Haven, United States, 2Instittuto CAICI, Rosario, Argentina, 3Orlando Immunology Center, Orlando, United States, 4Department of Infectious Diseases, Saint-Louis Hospital and University of Paris Diderot Paris 7, Paris, France, 5Tarrant County Infectious Association, Fort Worth, United States, 6University Hospital, Nantes, France, 7FUNDAI and University of Buenos Aires, Buenos Aires, Argentina, 8Bristol-Myers Squibb, Global Development and Medical Affairs, Wallingford, United States, 9Merck Research Laboratories, North Wales, United States
Background: Nucleoside and ritonavir (RTV) toxicities have led to interest in NRTI- and RTV-sparing regimens. SPARTAN is a multicenter, randomized, open-label, non-comparative pilot study to evaluate the efficacy and safety of an investigational NRTI- and RTV-sparing regimen of ATV experimental dose of 300mg BID plus RAL 400mg BID (ATV+RAL) in treatment-naïve HIV-infected subjects.
Methods: Subjects with HIV-RNA ≥ 5,000 c/mL were randomized 2:1 to ATV+RAL (n=63) or reference regimen of ATV/RTV 300/100mg QD + tenofovir/emtricitabine (TVD) 300/200mg QD (n=31). Primary analysis at week 24 (HIV-RNA < 50c/mL) uses confirmed virologic response (CVR NC=F).
Results: Week 24 efficacy results are listed below:
[Table 1: Efficacy at Week 24]
| ||HIV RNA < 50 c/mL n/N (%)||HIV RNA < 400c/mL n/N (%)|
| ||ATV + RAL||ATV/RTV + TVD||ATV + RAL||ATV/RTV + TVD|
|CVR (NC=F)||47/63 (74.6)||19/30 (63.3)||52/63 (82.5)||26/30 (86.7)|
|CVR (NC=M)||47/58 (81.0)||19/27 (70.4)||52/58 (89.7)||26/27 (96.3)|
|VR-OC||41/52 (78.8)||19/25 (76.0)||46/52 (88.5)||24/25 (96.0)|
NC=F: Non-Completers=Failure NC=M: Non-Completers=Missing
VR-OC: Virologic Response-Observed Cases
50.5% of all subjects had baseline HIV RNA ≥ 100,000c/mL. Through week 24, 7/63 on ATV+RAL and 1/30 on ATV/RTV+TVD met criteria for resistance testing (virologic failures-VF with HIV-RNA ≥ 400c/mL). 4/7 (57.1%) VF on ATV+RAL developed RAL resistance. No ATV resistance was observed in either arm. Grade 2-4 treatment-related AE hyperbilirubinemia occurred in 19% (12/63) of subjects on ATV+RAL and 16.7% (5/30) on ATV/RTV+TVD; Grade 4 hyperbilirubinemia were 20.6% (13/63) and 0%, respectively. 3.2% (2/63) on ATV+RAL and 0% on ATV/RTV+TVD discontinued due to treatment-related AEs. ATV PK exposures (n=13) on ATV+RAL were higher than historically observed with ATV/RTV+TVD. RAL exposures were comparable to historical data.
Conclusions: Through week 24, the investigational regimen of ATV+RAL BID achieved efficacy rates consistent with current standard of care. Hyperbilirubinemia was consistent with previous ATV BID studies. Overall 6.3% (4/63) developed RAL resistance on the ATV+RAL regimen.
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