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Home > Treatment > HIV Meds Quarterly > Spring/Summer 2010 > Cobicistat
Novel Pharmacokinetic Booster Cobicistat (GS-9350)
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Novel Pharmacokinetic Booster Cobicistat (GS-9350)

Cobicistat (GS-9350) is an investigational pharmacokinetic (PK) enhancer that (like ritonavir) is a potent CYP 3A4 inhibitor, but (unlike ritonavir) lacks activity against HIV. It is being developed both as a PK booster for the protease inhibitor elvitegravir and as a booster for protease inhibitors. The present study, a small (n = 79) randomized, double-blind Phase 2 trial, compared efficacy and safety of cobicistat (150 mg daily) with that of ritonavir (100 mg daily); both were given in combination with atazanavir (300 mg daily) and emtricitabine/tenofovir in treatment-naive individuals.

At 24 weeks, by intention-to-treat analysis, rates of HIV RNA suppression to <50 copies/mL were equivalent (84% for atazanavir/cobicistat recipients and 86% for atazanavir/ritonavir recipients). The mean increase in CD4 cell count also was roughly the same for the two groups: 203 cells/µL and 199 cells/µL, respectively.

Overall rates of adverse events were about the same in the two groups (20% for cobicistat subjects and 24% for ritonavir subjects), and rates of bilirubin increase (caused by atazanavir) were about the same. Cobicistat was associated with somewhat higher rates of nausea but lower rates of diarrhea. Cobicistat also was associated with higher rates of Grade 1 increases in serum creatinine and nearly equivalent decreases in estimated glomerular filtration rate (eGFR) (-15 mL/min compared with -14 mL/min for ritonavir recipients).

Further analysis (by Gilead, the manufacturer) of the effects of cobicistat on renal function in HIV-uninfected subjects showed decreases in eGFR but no changes in actual GFR (as measured by clearance of iohexol). Researchers suggested that cobicistat may inhibit the renal tubular secretion of creatinine but does not impact glomerular filtration.

Clinical Bottom Line
Although the availability of a PK booster other than ritonavir would be welcome, both the efficacy and safety profile of cobicistat require further evaluation. The concerns, raised by the results of this study as well as those of the elvitegravir/cobicistat ("Quad" pill) trial (also in this issue, see "Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir ['Quad' Pill] in Initial Therapy"), regarding increased creatinine levels and decreased eGFR must be elucidated, and practical (and inexpensive) means of distinguishing true declines in GFR from the possibly artifactual decreases in eGFR must be found. This issue may be of particular importance for patients who are receiving tenofovir or other medications that may cause decreases in GFR.

References

  1. Cohen C, Shamblaw D, Ruane P, et al. Single-tablet, fixed-dose regimen of elvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS-9350 achieves a high rate of virologic suppression and GS-9350 is an effective booster. In: Program and abstracts of the 16th Conference on Retroviruses and Opportunistic Infections; February 16-19, 2010; San Francisco. Abstract 58LB.
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