October 8, 2013
Significant improvements in lipid values were seen among HIV-infected patients who switched from a boosted protease inhibitor (PI)-based antiretroviral regimen to the fixed-dose combination of rilpivirine/tenofovir/emtricitabine (Complera), according to research presented at IDWeek 2013.
The SPIRIT study was primarily designed to establish the non-inferiority of rilpivirine/tenofovir/emtricitabine compared to regimens consisting of a PI, ritonavir (Norvir) and two NRTIs; favorable 24-week data on that front were presented last year. One of the study's secondary aims was to assess volunteers' relative change in fasting lipids -- specifically total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides -- depending on whether they switched from the PI-based therapy to rilpivirine/tenofovir/emtricitabine. At IDWeek, Pablo Tebas, M.D., presented encouraging 48-week data on that question.
To quickly recap the study construction: SPIRIT is a randomized, open-label, phase 3b study involving a total of 476 patients who began the study with a viral load below 50 copies/mL for at least the past six months while on a boosted-PI regimen. (The PI in the regimen was usually atazanavir [Reyataz], lopinavir or darunavir [Prezista]; the NRTIs in the regimen were usually tenofovir/emtricitabine [Truvada] or abacavir/lamivudine [Epzicom].)
A third of the volunteers (159) were randomized to continue their boosted-PI regimen for 24 weeks, then switch to rilpivirine/tenofovir/emtricitabine; the rest of the volunteers (317) switched to rilpivirine/tenofovir/emtricitabine immediately. Snapshots of both arms were taken at 24 and 48 weeks to assess CD4+ cell count, viral load, lipid values and other data.
This was a relatively diverse study cohort: Median age was in the low 40s, roughly 88% were male and 77% were white (the rest were about evenly split between African American and Latino). This was also a pretty healthy group: Mean CD4+ cell count at baseline was 576 cells/mm3 in the immediate-switch group and 600 in the delayed-switch group.
A snapshot (intent-to-treat) analysis at 48 weeks showed demonstrable fasting lipid reductions among all volunteers, with similar changes among those who immediately switched to rilpivirine/tenofovir/emtricitabine and those whose switch was delayed until week 24. Most of the reductions occurred within the first 24 weeks of the switch. "You see improvements in lipids that are similar to what you will obtain by starting a statin," Tebas said.
|Total Cholesterol Change (in mg/dL)||LDL Cholesterol Change (in mg/dL)||Triglycerides Change (in mg/dL)||TC:HDL Ratio Change|
|Delayed-Switch Group: Week 24 (Still on PI Regimen)||-1||0||+3||+0.08|
|Delayed-Switch Group: Week 48 (24 Weeks Post-Switch)||-25||-15||-81||-0.44|
|Immediate-Switch Group: Week 24||-25||-16||-54||-0.27|
|Immediate-Switch Group: Week 48 (Cumulative)||-24||-16||-65||-0.36|
From a clinical-relevance standpoint, the even more noteworthy findings may be regarding the proportion of patients with high or borderline-high dyslipidemia. Here, Tebas presented 24-week data only, comparing them to baseline.
Among patients who delayed their regimen switch, the proportion with undesirable lipid levels remained steady, while among patients who immediately switched, the proportions shifted dramatically (P < .001 in all cases within the chart below, when comparing between study arms at week 24):
|Delayed-Switch Group: Baseline||Delayed-Switch Group: 24 Weeks (Still on PI Regimen)||Immediate-Switch Group: Baseline||Immediate-Switch Group: 24 Weeks|
|% With Borderline-High Total Cholesterol (200 to 239 mg/dL)||31%||31%||29%||14%|
|% With High Total Cholesterol||10%||12%||12%||3%|
|% With Borderline-High LDL (130 to 159 mg/dL)||22%||22%||24%||15%|
|% With High LDL||13%||15%||13%||4%|
|% With Borderline-High Triglycerides (150 to 199 mg/dL)||31%||31%||29%||14%|
|% With High Triglycerides||10%||12%||12%||3%|
No significant differences in changes were seen for HDL cholesterol.
In response to a question from the audience, Tebas noted that the use of lipid-lowering agents had been permitted for patients enrolled in the study, but that his recollection was that a "very small proportion" -- less than 10% -- of volunteers were receiving such treatment. The number of patients taking lipid-lowering drugs were similar between the two groups.
It's worth keeping in mind that these are clinical trial data (real-world mileage always may vary), and that the study was funded by the company marketing rilpivirine/tenofovir/emtricitabine in the U.S. In addition, although some volunteers were receiving statins through the normal course of their health care, this study did not in any other way seek to use interventions that may have yielded reductions in fasting lipids without switching therapy. Further, potential lipid effects are but one of many considerations a clinician must take into account when determining whether it is worthwhile to switch a patient on suppressive antiretroviral therapy to a new regimen.
Nonetheless, these findings provide further support for the favorable lipid profile of rilpivirine/tenofovir/emtricitabine relative to some of the more commonly prescribed boosted-PI regimens.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.
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