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Safety Analysis Gives Edge to Elvitegravir vs
Efavirenz or Atazanavir at 96 Weeks
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53rd ICAAC, September 10-13, 2013, Denver
Mark Mascolini
After 96 weeks in two trials that randomized antiretroviral-naive adults to one of three currently popular regimens, an elvitegravir-based combination (Stribild) had a better neuropsychiatric and rash profile than efavirenz-containing Atripla and a better gastrointestinal profile than atazanavir/ritonavir plus tenofovir/emtricitabine (TDF/FTC) [1]. People taking atazanavir/ritonavir had significantly fewer abnormal dreams than people taking Stribild.
Combining the integrase inhibitor elvitegravir with the booster cobicistat and TDF/FTC, Stribild is licensed as a one-pill once-daily treatment for antiretroviral-naive adults. In two trials that enrolled previously untreated people, Stribild proved noninferior to Atripla (efavirenz/TDF/FTC) [2] and noninferior to atazanavir/ritonavir plus TDF/FTC [3].
To compare safety and tolerability of the three regimens through 96 weeks, researchers conducted this analysis of treatment-emergent adverse events. They focused on common adverse events, defined as those affecting at least 10% of participants in any treatment arm. Key endpoints were statistically significant differences in common adverse events between the Stribild arm and the comparison arms. The investigators pooled the 701 Stribild patients of the two trials and compared them with 352 people randomized to Atripla and 355 randomized to atazanavir.
The study group was relatively young, averaging 38 or 39 years in all three treatment groups. About 90% in all arms were men. The Stribild and Atripla groups had a higher proportion of blacks (25% and 26%) than the atazanavir group (13%). Median pretreatment viral loads in the Stribild, Atripla, and atazanavir groups were 4.78, 4.78, and 4.86 log10 copies/mL, and median initial CD4 counts were 377, 382, and 375. Everyone entered the two trials with an estimated glomerular filtration rate at or above 70 mL/min.
Among study-defined common adverse events, most were grade 1 and occurred by week 4. Cumulative prevalence of common adverse events of any grade that differed significantly between the Stribild arm and the two comparison arms through 96 weeks were insomnia, abnormal dreams, rash, dizziness, nausea, headache, diarrhea, and ocular icterus (jaundice in the whites of the eyes), as indicated in the following list:
Cumulative prevalence of common adverse events with Stribild, Atripla, and ATV/r through 96 weeks:
Insomnia: STB 10%, ATR 16%,* ATV 7%
Abnormal dreams: STB 9%, ATR 28%,* ATV 4%**
Rash: STB 8%, ATR 14%,* ATV 9%
Dizziness: STB 7%, ATR 26%,* ATV 8%
Nausea: STB 21%, ATR 15%,* ATV 21%
Headache: STB 16%, ATR 11%,* ATV 15%
Diarrhea: STB 25%, ATR 24%, ATV 31%**
Ocular icterus: STB <1%, ATR 0%, ATV 14%**
*P < 0.05 for Stribild versus Atripla.
**P < 0.05 for Stribild versus atazanavir/ritonavir.
Continuing prevalence of common treatment-emergent adverse events at 96 weeks confirmed less frequent neuropsychiatric problems with Stribild than with Atripla and less frequent diarrhea with Stribild than atazanavir/ritonavir, as the next list shows:
Continuing prevalence of common adverse events with Stribild, Atripla, and ATV/r through 96 weeks:
Insomnia: STB 6.3%, ATR 8.4%, ATV 5.9%
Abnormal dreams: STB 4.1%, ATR 14.2%, ATV 1.3%
Rash: STB 1.7%, ATR 1.7%, ATV 0.3%
Dizziness: STB 1.5%, ATR 4.1%, ATV 0.7%
Nausea: STB 3.8%, ATR 3.0%, ATV 3.6%
Headache: STB 4.8%, ATR 2.4%, ATV 4.6%
Diarrhea: STB 4.5%, ATR 4.7%, ATV 9.2%
Ocular icterus: STB 0%, ATR 0%, ATV 6.9%
Continuing nausea and headache were marginally more frequent with Stribild than with the other two regimens. Low proportions of study participants dropped out of the trials because of adverse events, but these rates were significantly lower for Stribild for two adverse events: neuropsychiatric (Stribild <1% versus Atripla 3%, P = 0.002) and rash (Stribild <1% versus Atripla 1%, P = 0.045; and Stribild <1% versus atazanavir/ritonavir 1%, P = 0.046).
The investigators concluded that through 96 weeks of treatment, Stribild has a better neuropsychiatric and rash profile than Atripla and a better diarrhea profile than atazanavir/ritonavir. They suggested that clinicians should consider such long-term problems when picking a first-line regimen because antiretroviral therapy "is currently a life-long commitment."
References
1. Shalit P, Gallant J, Mills A, et al. Long-term tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir DF compared to efavirenz/emtricitabine/tenofovir DF or ritonavir-boosted atazanavir plus emtricitabine/tenofovir DF in treatment-naive HIV-1-infected subjects. 53rd ICAAC. September 10-13, 2013. Denver. Abstract H-671.
2. Zolopa A, Sax PE, DeJesus E, et al. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;63:96-100.
3. Rockstroh JK, DeJesus E, Henry K, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62:483-486.
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