Is QUAD the new black?

Session 26 on Wednesday was " State of ART and drug resistance” did not launch any new blockbuster antiretroviral – unlike some previous World AIDS or CROIs. However there was the first phase 3 results presented for QUAD.

Paper 101 is a 48 week phase 3 data on QUAD – Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (trying saying that after 3 Seattle micro-brewery Pale Ales) versus Atripla involving 700 treatment naive patients. Quad was non-inferior to EFV/FTC/TDF with 88% and 84%, respectively, having viral suppression at week 48. Virologic failure rates at week 48 were 7% in both arms. Of AE occurring in ≥10% of subjects nausea was significantly more frequent in Quad than EFV/FTC/TDF, while dizziness, abnormal dreams, insomnia and rash were significantly less common in Quad than EFV/FTC/TDF. Of note creatinine clearance decrease was significantly greater than with EFV/FTC/TDF (–14.3 vs –3.0 mL/min by week 48).

A parallel phase 3 study is to be presented on Thursday (627) with the comparator arm being booster atavanavir /FTC/TDF in 708 treatment naive patients. Quad was non-inferior to EFV/FTC/TDF with 90% and 87% respectively, having viral suppression at week 48. Virologic failure rates at week 48 were 5% in both arms. Of AE occurring in ≥10% of subjects elevated bilirubin was significantly more frequent in the atavanavir arm. Of note creatinine clearance decrease was significantly greater than with the atavanavir arm (–12.7 vs –9.5 mL/min by week 48).

So in summary QUAD is a highly effective new STR (single tablet regimen) for HIV therapy. A concern is the decline in renal function with QUAD found in both studies which remains to be fully explained.