SPARTAN: Ein unkonventioneller Versuch von Atazanavir + Raltegravir zweimal täglich (TH LB B204)

Im Kampf um die beste Therapiekombination wird nun alles versucht. Eine Studie (Kozal et al, LB B204) wollte einen Versuch ohne NRTIs und ohne boosting starten. Die Zweier-Kombination Raltegravir und unboosted Atazanavir sollte mit einer Standard-Therapie (ATV/r+Truvada) verglichen werden. Die Resultate waren zwar gut für die neue Therapie, doch die zweimal tägliche Einnahme dürfte längerfristig der Therapiemodalität keine grossen Fans beisteuern.
Interessant aber die Feststellung, dass 2x300mg Atazanavir kombiniert mit Raltegravir zu Blutspiegeln führt, die sogar höher als diejenigen bei boostet Atazanavir sind (einmal tgl).

Links: Kozal, et.al. – THLBB204 / Slides mit Audio / Präsentation (.ppt)

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

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: [tab_02]
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.