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Switching From ABC/3TC to TDF/FTC Cuts Lipids in Randomized Trial
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Trading coformulated abacavir/lamivudine (ABC/3TC) plus efavirenz for coformulated tenofovir, emtricitabine, and efavirenz (Atripla) swiftly lowered lipids in people with high cholesterol in the 24-week randomized ASSERT trial [1]. Graeme Moyle (Chelsea and Westminster Hospital, London) and colleagues believe the lipid improvements after the switch "may have a positive impact on calculated coronary heart disease risk" in these people.
ASSERT's primary objective was to see whether switching from ABC/3TC plus efavirenz to Atripla would reduce fasting total cholesterol in 12 weeks. This open-label study enrolled 157 people taking coformulated ABC/3TC plus efavirenz for at least 6 months with a viral load below 50 copies for at least 12 weeks and total cholesterol at or above 5.2 mmol/L (about 200 mg/dL). At study week 12 the 78 people who had continued ABC/3TC plus efavirenz to that point switched to Atripla and follow-up in everyone continued to week 24.
Median age in the two study groups was 42 to 44 years, about 60% were white, and about 80% were men. Median fasting total cholesterol stood at 6.19 mmol/L in the ABC/3TC group and 6.62 mmol/L in the Atripla group (about 240 and 256 mg/dL). More than 90% in both treatment arms completed week 24.
In the first 12 weeks of the study, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides remained stable in the ABC/3TC group while falling significantly in people who switched to Atripla. Twelve weeks later, people originally randomized to Atripla maintained these improvements, while people who switched to Atripla at week 12 had declines equivalent to those of the original switch group. In the week-12 analysis, all lipid improvements in the switch group were statistically significant (-0.87 versus +0.01 mmol/L for total cholesterol, -6.57 versus -0.02 mmol/L for LDL cholesterol, and -6.28 versus -0.63 mmol/L for triglycerides, all P < 0.001). The total-to-high-density lipoprotein ratio improved moderately throughout the study.
In the group originally randomized to Atripla, the proportion with high fasting cholesterol by NCEP guidelines (above 200 mg/dL) fell from 64% at study entry to 30% at week 24. In the group that switched to Atripla at week 12, the proportion with high cholesterol sank from 48% at study entry to 13% at week 24.
No one in either study arm met trial criteria for virologic failure--two consecutive viral loads above 400 copies. CD4 counts remained stable throughout the study. No one in either group had a grade 3 or 4 renal abnormality during the trial, and no one dropped out because or renal side effects.
Moyle and colleagues concluded that the switch from coformulated ABC/3TC plus efavirenz to Atripla "leads to a significant, rapid decline in lipid parameters towards desirable levels (per NCEP guidelines)." They rated this switch strategy "appropriate in the management of hypercholesterolemic patients."
A double-blind placebo-controlled AIDS Clinical Trials Group study found that adding tenofovir to a stable regimen significantly improved nonhigh-density lipoprotein cholesterol, LDL cholesterol, and total cholesterol HIV-infected people with abnormal lipids [2].
References
1. Moyle G, Orkin C, Fisher M, et al. Switching from Kivexa + efavirenz to Atripla reduces total cholesterol in hypercholesterolemic subjects: final results of a 24-week, randomized trial. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract P080.
2. Tungsiripat M, Kitch D, Glesby MJ, et al. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS. 2010;24:1781-1784
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