September 15, 2012
Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir, colloquially known as "Quad") shows slightly better effectiveness and tolerability than either Atripla (efavirenz/tenofovir/emtricitabine) or a regimen comprised of ritonavir (Norvir)-boosted atazanavir (Reyataz) plus Truvada (tenofovir/emtricitabine), according to combined results from three 48-week studies presented at ICAAC 2012.
The analysis encompassed data from the two phase 3 pre-approval trials for Stribild, as well as one phase 2 study. In total, the trials followed 1,479 HIV-infected individuals who had no prior treatment experience; 749 were put on Stribild, 375 on Atripla and 355 on ritonavir-boosted atazanavir plus Truvada. The average ages of the groups were 37, 38 and 39 respectively. About 90% of each group were men and one third or fewer were non-white.
In a snapshot analysis taken at the end of 48 weeks on treatment, the Stribild group showed the highest percentage of virologic suppression (defined in this study as a viral load below 50 copies/mL). The on-Stribild suppression rate of 88.8% was significantly higher than the 84.0% for the Atripla group (P = .016) and trended higher than the 86.6% for the ritonavir-boosted atazanavir group (P = .37). CD4+ cell count gains were strong for all groups after 48 weeks, but tended to favor Stribild; the average gain of 224 cells/mm3 for Stribild was slightly better than the gain of 203 cells/mm3 for Atripla (P = .081) and 211 cells/mm3 for ritonavir-boosted atazanavir (P = .24).
These results reinforce Stribild's noninferiority when compared to the other two groups, which are preferred first-line regimens in the United States. Additionally, Stribild's efficacy proved consistent across subgroups with different ages, race, gender, baseline viral loads and baseline CD4+ cell counts.
All three regimens were generally well tolerated and side effects were usually mild to moderate. The rate of adverse events that led to treatment discontinuation was 3.5% for Stribild, 5.1% for Atripla and 5.1% for ritonavir-boosted atazanavir. Moreover, across the three groups, the rates of any serious adverse events were similar at 9.2%, 6.7% and 8.7%, respectively, while death rates were also similar at 0.1%, 0.5% and 0.8%, respectively. Nausea and insomnia rates were about the same across all three groups.
It is worth noting, however, that the tally of some adverse events differed in expected ways. Those in the Atripla group reported abnormal dreams more frequently than in the other two groups, as well as more dizziness, rashes and depression. Hyperbilirubinemia was dramatically more common among those in the ritonavir-boosted atazanavir group than the other two groups. Elevated creatine kinase levels were more common within the Atripla group than the other two groups, as were elevated gamma-glutamyl transpeptidase levels, a marker for liver function.
The researchers noted increases in creatinine (a marker for renal function) with the Stribild group beginning as early as two weeks after starting treatment. However, levels remained stable through week 48, and the researchers stated that an "early small increase in creatinine that stabilizes is expected with [Stribild] due to cobicistat's inhibition of renal creatinine tubular secretion." At the same time, the researchers proposed that the small increase (up to 0.4 mg/dL) was unlikely caused by cobicistat itself.
In terms of lipid values, median total, HDL and LDL cholesterol levels all rose significantly less with Stribild than with Atripla, but rose similarly between Stribild and ritonavir-boosted atazanavir. Triglycerides rose significantly less with Stribild than ritonavir-boosted atazanavir, but rose similarly between Stribild and Atripla.
Stribild was approved last month by the U.S. Food and Drug Administration (FDA) for first-line treatment in HIV-infected individuals. The FDA lists nausea and diarrhea as common side effects, while more serious side effects include kidney problems, decreased bone mineral density, fat redistribution and immune system changes.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
Follow Warren on Twitter: @WarrenAtTheBody.