Updated Results on Quad: 96-Week Data From Phase 3 Studies

Two oral presentations presented 96 week data from the two phase 3 treatment studies for the recent approval of the single-tablet, four-drug combination of elvitegravir/cobicistat/tenofovir/FTC, developed as Quad, and now approved as Stribild in the U.S.

Entry criteria for both studies included being treatment-naive and having an eGRF >70 mL/min/1.73m².

The first study comparing Quad to Atripla, reported similar rates of virologic suppression to <50 copies/mL of 84% vs 82% (difference 2.7%, 95% CI -- 2.9% to 8.3%). This compared to 48-week results of 88% vs 84%, difference (3.6%, 95% CI -1.6% to 8.8%). A sub-group analysis, by baseline viral load below and above 100,000 copies/mL report rates of81% vs 83%. Mean CD4 cell increases were 295 vs 273 cells/mm³.¹

Discontinuation rates due to side effect were similar in each arm (5% vs 7%) with greater reporting of CNS side effects (47% vs 66%) and rash (21% vs 31%) with Atripla but higher rates of renal discontinuations with Quad (2%; n=7 vs 0).

Two patients discontinued Quad after week 48 due to serum creatinine increases but without features of proximal renal tubulopathy. Median changes in serum creatinine (mmol/L [mg/dL]) at week 96 in the Quad vs Atripla arms (11.5 vs 0.9 [0.13 vs 0.01]) were similar to those at week 48 (12.4 vs 0.9 [0.14 vs 0.01]).

Quad had smaller median increases (mmol/L [mg/dL]) in total (0.23 vs 0.47 [9 vs 18], p<0.001) and LDL cholesterol (0.23 vs 0.41 [9 vs16], p=0.011), and similar increase in triglycerides (0.05 vs 0.09 [4 vs 8], p=0.41).

In the second study, 96-week results were reported comparing Quad to the boosted PI combination of atazanavir/ritonavir plus tenofovir/FTC, in just over 700 treatment-naive patients.

The proportion of patients with viral load <50 copies/mL at week 96 was 83% vs 82% (difference 1.1%; 95% CI: 4.5%, 6.7%). This compared to 90% vs 87% (difference 3.0%; 95% CI: 1.9% to 7.8%) at week 48, finding Quad to be non-inferior at both timepoints. Results in patients with baseline viral load >100,000 copies/mL were 82% vs 80% (all comparisons, Quad vs ATZ/r respectively).

Mean CD4 cell increases at week 96 were also similar between arms (256 vs 261 cells/mm³).

Discontinuation rates due to side effects were 4% vs 6%, and caused by renal complications in 3 (0.8%) vs 2 (0.6%) of patients. One person in each arm discontinued between week 48 and 96 due to elevated serum creatinine.

Resistance was reported in 2% vs <1% of patients.

Median increases from baseline in serum creatinine (mmol/L [mg/dL]) at week 96 (10.6 vs 7.1 [0.12 vs 0.08]) were similar to those at week 48 (10.6 vs 7.1 [0.12 vs 0.08]).

Quad had smaller increases (mmol/L [mg/dL]) in triglycerides (0.06 vs 0.18 [5 vs 16], p=0.012) but greater increases in total cholesterol (0.36 vs 0.21 [14 vs 8], p=0.046) with similar changes in LDL and HDL cholesterol. Quad had smaller mean decreases (%) in BMD (hip: 3.16 vs -4.19, p=0.069, spine: 1.96 vs 3.54, p=0.049).

References

1. Zolopa A et al. Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to efavirenz/emtricitabine/tenofovir DF at week 96 in treatment-naive HIV-1-infected patients. Oral abstract O424A.
2. 2. Fordyce M et al. Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to atazanavir boosted by ritonavir plus emtricitabine/tenofovir DF at week 96 in treatment-naive HIV-1-infected patients. Oral abstract O424B.

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