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HIV11: Stribild Matches Efficacy and Tolerability of Atripla or Boosted Atazanavir at 96 Weeks

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The Stribild single-tablet-regimen -- formerly dubbed the Quad -- demonstrated "robust and durable" efficacy and continued to be well-tolerated through 96 weeks, according to findings from 2 studies presented at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) this month in Glasgow.

Gilead Science's recently approved 4-in-1 coformulation contains the next-generation integrase inhibitor elvitegravir, the novel boosting agent cobicistat, and tenofovir/emtricitabine (the drugs in Truvada). On August 27 the U.S. Food and Drug Administration approved Stribild for treatment-naive HIV positive adults. Approval was based on study data showing that Stribild suppresses HIV viral load as effectively as 2 widely used combinations listed as preferred regimens in the U.S. DHHS antiretroviral treatment guidelines.

At the Glasgow meeting researchers presented further follow-up data from Study 102, comparing Stribild against the Atripla (efavirenz/tenofovir/emtricitabine) single-tablet regimen, and Study 103, a comparison against ritonavir-boosted atazanavir (Reyataz).

Both Phase 3 trials enrolled similar patient populations. About 90% were men, the majority were white, and the average age was 38 years. Participants were starting HIV treatment for the first time, the mean CD4 T-cell count was approximately 375 cell/mm3, and only about 13% had < 200 cell/mm3. Baseline kidney function was normal and 5% or less were coinfected with hepatitis B or C.

In each study, about 700 participants were randomly assigned (1:1) to receive either Stribild or the comparator regimen once-daily.

As previously reported at prior conferences and described in the June 30, 2012, issue of The Lancet, Stribild matched both established regimens in terms of efficacy, with at least 80% of participants in both arms of both studies achieving undetectable HIV viral load (< 50 copies/mL) at 48 week. Similar proportions of patients in both studies discontinued therapy due to adverse events by week 48.

96-week Results

  • All studied regimens continued to suppress HIV through 96 weeks:

o   Stribild vs Atripla: 84% vs 82%;

o   Stribild vs atazanavir/ritonavir: 83% vs 82%.

  • Virological failure rates also remained similar:

o   Stribild vs Atripla: 6% vs 8%;

o   Stribild vs atazanavir/ritonavir: 7% vs 7%.

  • Stribild was statistically equivalent to either Atripla or atazanavir/ritonavir when stratifying participants by age, sex, race, baseline viral load, and CD4 cell count.
  • CD4 cell gains were similar across treatment arms:

o   Stribild vs Atripla: 295 vs 273 cells/mm3;

o   Stribild vs atazanavir/ritonavir: 256 vs 261 cells/mm3.

  • Emergence of drug resistance was rare (1%-2%) in both studies.
  • Stribild remained well tolerated through 96 weeks, with rates of serious adverse events (SAEs) remaining similar:

o   Stribild vs Atripla: +4% (added to 12% at week 48) vs +5% (added to 9% at week 48);

o   Stribild vs atazanavir/ritonavir: +2% (added to 7% at week 48) vs +3% (added to 7% at week 48).

  • Discontinuations due to adverse events rose by just 1%-2% across arms.
  • In Study 102, gastrointestinal side effects were more common in the Stribild arm, while Atripla recipients were more likely to report neuropsychiatric symptoms such as abnormal dreams and dizziness (attributed to efavirenz).
  • In Study 103, side effects were generally similarly distributed in the 2 arms, but atazanavir recipients were more likely to experience ocular icterus, or yellowing of the eyes due to elevated bilirubin.
  • Estimated GFR (a marker of kidney function) remained stable in all arms from week 48 through week 96.
  • In Study 103, bone density -- which had fallen from baseline through week 48 in both treatment arms -- remained stable through week 96.

In summary, the investigators for both studies concluded that Stribild showed "robust and durable efficacy through week 96," which was consistent across subgroups of high and low viral load and CD4 cell counts. There were "low rates of resistance" in both studies.

Both research teams concluded that "Stribild was well-tolerated through week 96," with "no new cases of proximal tubulopathy" and "no further reductions in GFR" relative to week 48.

11/27/12

References

A Zolopa, J Gallant, C Cohen, 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. 11th International Congress on Drug Therapy in HIV Infection (HIV11). Glasgow, November 11-15, 2012. Abstract O424A.

J Rockstroh, E DeJesus, K Henry, 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. 11th International Congress on Drug Therapy in HIV Infection (HIV11). Glasgow, November 11-15, 2012. Abstract O424B.

Other Source

Gilead Sciences. Gilead ’s Once-Daily Single Tablet Regimen Stribild Maintains High Viral Suppression Through Two Years of Therapy Among Treatment-Naïve HIV Patients. Press release. November 15, 2012.