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,
(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.
receiving the Quad pill experienced a more rapid decline
in HIV viral load compared with Atripla recipients.
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.
in both arms experienced similar CD4 cell gains (about
Quad pill was generally safe and well tolerated.
recipients had lower frequencies than Atripla recipients
of central nervous system symptoms (17% vs 26%, respectively)
and psychiatric side effects (10% vs 44%).
half as many participants in the Quad arm discontinued
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.
on these findings, the study authors concluded, "Once-daily
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.
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.