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Single-Pill Rilpivirine Regimen Maintains Suppression After Switch From Boosted PI
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53rd ICAAC, September 10-13, 2013, Denver
Mark Mascolini
Switching from a ritonavir-boosted protease inhibitor (PI) to the once-daily single-tablet combination of rilpivirine plus tenofovir/emtricitabine (Complera or Eviplera) maintained viral suppression through 48 weeks in a 476-person open-label trial, SPIRIT [1]. Complera also controlled HIV in a subanalysis of 83 black participants.
Simplifying a multipill regimen can reduce toxicities and improve adherence, thereby enhancing chances for long-term virologic control. To assess the activity of Complera as a substitute for a boosted PI combination, SPIRIT enrolled 476 adults taking a boosted PI plus two nucleosides for at least 6 months with a viral load below 50 copies. The baseline regimen could be a person's first or second combination. Because rilpivirine is a nonnucleoside, participants could have no nonnucleoside experience.
The investigators randomized 317 participants to switch to Complera and 159 to continue their PI regimen for 24 weeks. At week 24 the PI group switched to Complera, and everyone took Complera through week 48. The primary endpoint was a viral load below 50 copies at week 24 with the snapshot analysis. The aim was to determine whether switching to Complera is noninferior to continuing a boosted PI, defined by a 12% margin.
Baseline values were similar in the switch-to-Complera group and the continued-PI group, with median ages of 42 and 43, 86% and 91% male, 76% and 78% white, 19% and 14% black, and 16% and 20% Latino. Median time since first antiretroviral therapy measured 2.9 years in the Complera group and 2.6 years in the PI group; respective average CD4 counts were 576 and 600. About one third of participants were taking atazanavir, one third lopinavir, and one fifth darunavir. While 81% were taking tenofovir/emtricitabine, 13% were taking abacavir/lamivudine.
In the week-24 snapshot analysis, 93.7% randomized to Complera and 89.9% randomized to continue their PI had a viral load below 50 copies. The 3.8% difference (P = 0.15) established the noninferiority of switching from a boosted PI to Complera. Among white participants, snapshot 24-week 50-copy response rates were 93.4% with Complera and 89.5% with a continued PI, also a 3.8% difference (P = 0.22). Among black participants, the 24-week response rates were 95.1% with Complera and 90.9% with a continued PI, for a 4.2% difference (P = 0.60). In the 24-week analysis there were 3 virologic failures (2 in whites and 1 in blacks) in the Complera group and 8 virologic failures (7 in whites and none in blacks) in the continued-PI group.
The week-48 sub-50-copy response rate was 89.3% in people who switched to Complera on day 1. Among people who switched at week 24, the week 24- to 48-week response rate was 92.1%. In black trial participants week-48 sub-50-copy rates were 88.5% in the immediate-switch group and 95.0% from week 24 to 48 in the delayed-switch group.
No one who continued a boosted PI for 24 weeks discontinued because of adverse events in those 24 weeks, as might be expected in a population already tolerating a boosted PI. In the group that switched immediately to Complera, there were 7 discontinuations for adverse events (2.2%) through week 48, all of them in whites. In the group that switched to Complera at week 24, there were 6 discontinuations (3.9%) between week 24 and 48, 5 in whites and 1 in blacks.
Overall rates of grade 3 or 4 adverse events were 5.7% in the immediate-switch group through week 48, 6.9% in the continued-PI group through week 24, and 7.9% in the delayed-switched group from week 24 through week 48. These rates did not differ substantially between blacks and whites. Estimated glomerular filtration rate changed little in the immediate- or delayed-switch group. Swapping a PI for Complera improved fasting triglycerides, low-density lipoprotein cholesterol, and total-to-high-density lipoprotein cholesterol ratio in whites and blacks.
Reference
1. Mounzer K, Palella F, Slim J, et al. SPIRIT: Simplifying to rilpivirine/emtricitabine/tenofovir DF single-tablet regimen from boosted protease inhibitor regimen maintains HIV suppression in the black subgroup. 53rd ICAAC. September 10-13, 2013. Denver. Abstract H-656.
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