There was a lot of really good information today, not just from this stream but several others and I will be adding more over the next 2 days. But for now, here is GARDEL at 96 weeks
GARDEL 96 weeks
The 96 week data of this argentinian study was presented to show durability of the novel nucleoside sparing bicombo of 3TC/LPV/r.
The 48 week data was presented at this same meeting in Brussels 2013 by Pedro Cahn
426 naïve patients were randomised to receive a 3 drug regimen of 2NRTI/LPV/r or the novel 2 drug regimen of 3TC/LPV/r.
Virological efficacy of the nuc sparing arm was equivalent to the 3 drug arm at 96 weeks, 90% vs 84% (CI95: -2.3% to 14.1%). Equivalence in the high viral load stratum >100K which we saw at 48 weeks was also maintained here.
It needs to be said however that AZT/3TC accounted for 54% of the NRTI backbones in the 3 drug arm. One could therefore expect AZT toxicity discontinuations leading to underperformance of the 3 drug arm bringing about equivalence with 3TC/LPV/r in this ITT analysis. This makes the overall study findings questionable. The analysis of protocol defined virological failures (PDVF) and resistance is however reassuring. For 3TC/LPV/r vs 2NRTI/LPV/r, PDVFs were 7 vs 6% with 4 vs 3 cases of M184V but no other NRTI RAMs or primary PI RAMs.
The other downside of course is that LPV/r is not really standard of care considering other options and so this is not a regimen most clinicans would consider. Hence the pilot that I fed back on yesterday looking at 3TC/DTG instead which Pedro Cahn will now take into Phase 3 following success of the pilot.
The road to nuc sparing has been a rocky one with futility of the likes of RAL/ATV, MRC/ATV/r and MRC/DRV/r.
This study poses the question: “is the only good nuc sparing regimen the one with the nuc in it lol?!”. Not even. At least we still have RAL/DRV/r, although even this falls down in sicker patients (CD4<200 and VL>500K).
We do however eagerly watch the development of newer generation NNRTI/INSTI nuc sparing bicombos: CBV/RPV and DTG/RPV in LATTE and SWORD respectively.