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Gilead Quad Pill Works Better than Atripla

Gilead's elvitegravir "Quad" pill suppressed viral load as well as Atripla, but caused fewer neurological side effects.

The Quad pill is a coformulation containing the experimental integrase inhibitor elvitegravir, the novel boosting agent cobicistat (GS 9350), tenofovir, and emtricitabine. It is designed to be used as a once-daily single-tablet regimen.

As described in the March 27, 2011, issue of AIDS, Cal Cohen from the Community Research Initiative of New England and colleagues working with Gilead Sciences conducted a Phase 2 clinical trial to compare the Quad pill versus Atripla, the currently approved single-tablet regimen containing efavirenz, tenofovir, and emtricitabine (also made by Gilead).

The study included 71 previously untreated HIV positive participants who were randomly assigned (2:1) to take the Quad pill or Atripla once-daily for 48 weeks.

Most participants (about 90%) were men, the average age was about 35 years, and about 75% were white. All had a baseline viral load of at least 5000 copies/mL, a CD4 T-cell count > 50 cells/mm3 (mean of about 400 cells/mm3), and no resistance to the first 3 antiretroviral drug classes.

Results

  • Participants receiving the Quad pill experienced a more rapid decline in HIV viral load compared with Atripla recipients.
  • In intent-to-treat analyses at both 24 and 48 weeks, 90% of participants in the Quad arm achieved viral load < 50 copies/mL, compared with 83% in the Atripla group.
  • Participants in both arms experienced similar CD4 cell gains (about 125 cells/mm3).
  • The Quad pill was generally safe and well tolerated.
  • Quad recipients had lower frequencies than Atripla recipients of central nervous system symptoms (17% vs 26%, respectively) and psychiatric side effects (10% vs 44%).
  • About half as many participants in the Quad arm discontinued therapy prematurely.
  • Participants receiving the Quad pill experienced decreases in estimated glomerular filtration rate (an indicator of possible kidney dysfunction) within the first few weeks, but remained within the normal range and did not worsen through week 24 or 48.
  • No participant experienced clinical adverse events or discontinued study drugs due to changes in serum creatinine or kidney function.

Based on these findings, the study authors concluded, "Once-daily [elvitegravir/cobicistat/emtricitabine/tenofovir] achieved and maintained a high rate of virologic suppression with fewer central nervous system and psychiatric adverse events compared to a current standard-of-care regimen of [efavirenz/emtricitabine/tenofovir]."

The main concern in this study was the signal of kidney toxicity related to cobicistat (the same was seen in another study comparing cobicistat vs ritonavir), given that tenofovir can also cause kidney problems in a small proportion of susceptible patients. The investigators argued, however, that cobicistat alters estimated but not actual glomerular filtration rate.

Investigator affiliations: Community Research Initiative of New England, Boston, MA; Whitman Walker Clinic, Washington, DC; Gilead Sciences, Foster City, CA.

4/5/11

Reference
C Cohen, R Elion, P Ruane, et al. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS 25(6):F7-F12 (abstract). March 27, 2011.