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Switching from ABC/3TC to TDF/FTC Trims Risk of Virologic Failure
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
People with a sub-200-copy viral load while taking abacavir/lamivudine (ABC/3TC) plus a boosted protease inhibitor (PI) had a lower risk of virologic failure in 48 weeks if they switched to tenofovir/emtricitabine (TDF/FTC) than if they continued ABC/3TC in the randomized SWIFT trial [1]. But the proportion of study participants who maintained a viral load below 200 copies was similar in the two treatment arms, and most protocol-defined failures reflected low-level viremia.
Three previous trials--ACTG A5202 [2], ASSERT [3], and BICOMBO [4]--found higher rates of virologic failure in people taking a regimen including ABC/3TC than in those taking TDF/FTC. Given these findings, SWIFT study investigators mounted this multicenter trial to see if people responding to a boosted PI plus ABC/3TC maintained viral control as well as those who switched from ABC/3TC to TDF/FTC.
SWIFT investigators enrolled 311 people with a viral load below 200 copies for at least 3 months and at screening while taking a ritonavir-boosted PI plus ABC/3TC for at least 3 months [1]. No one had a history of resistance to any study drugs, and participants could have any CD4 count. The researchers randomized 156 people to continue ABC/3TC and 155 to switch to TDF/FTC, while maintaining their PIs. The primary endpoint was the proportion of people with a viral load below 200 copies at week 48 in a time-to-loss-of-virologic-response (TLOVR) analysis (which considers virologic failure, premature discontinuation for any reason, or antiretroviral modification as failure). The researchers defined virologic failure as a confirmed rebound above 200 copies or the final study viral load above 200 copies.
Demographic and clinical characteristics were similar in the two study arms, with 85% of participants men, 28% African American, median age 46 years, and median CD4 count 532.
The same number of people in each treatment arm, 139 (89%) completed 48 weeks of study. One person stopped the ABC/3TC regimen because of lack of efficacy. In the primary analysis, a similar proportion in each treatment group had a viral load below 200 copies after 48 weeks--83% who continued ABC/3TC and 86% who switched to TDF/FTC. This result indicated that switching to TDF/FTC is not inferior to continuing ABC/3TC in patients like these.
Eleven people maintaining ABC/3TC versus 3 switching to TDF/FTC had protocol-defined virologic failure, a significant difference (P = 0.034). Among these 14 people with virologic failure, 8 people taking ABC/3TC and all 3 taking TDF/FTC had low-level viremia at week 48. Of the other 3 people with virologic failure while maintaining ABC/3TC, 1 had a viral load rebound but then regained viral control without switching drugs, and 2 discontinued treatment early. Genotyping virus from 3 of 14 people with virologic failure while continuing ABC/3TC disclosed no resistance mutations.
Three people (2%) in the ABC/3TC arm dropped out of the study because of adverse events, compared with 7 (5%) in the TDF/FTC arm. Rates of grade 3 or 4 adverse events were similar with ABC/3TC (10%) and TDF/FTC (8%). Only one person, who was taking TDF/FTC, had a grade 3 or 4 adverse event related to study drugs. Serious adverse event rates were 7% with ABC/3TC and 8% with TDF/FTC.
By both the MDRD method and the Cockroft-Gault method, estimated glomerular filtration rate declined in both treatment arms through 48 weeks, but significantly more with TDF/FTC than with ABC/3TC. The investigators rated these changes as having "unclear clinical significance." Low-density lipoprotein cholesterol and triglycerides improved significantly in people who switched to TDF/FTC. But the total to high-density-lipoprotein cholesterol ratio did not differ between the two study arms.
The SWIFT team concluded that switching from ABC/3TC (plus a boosted PI) to TDF/FTC maintains virologic suppression while cutting the risk of virologic failure.
References
1. Campo R, DeJesus E, Khanlou H, et al. SWIFT study: switching from lamivudine/abacavir (3TC/ABC) to emtricitabine/ tenofovir DF (FTC/TDF) maintained efficacy and reduced virologic failure. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract WELBB03.
2. Sax PE, Tierney C, Collier AC, et al; AIDS Clinical Trials Group Study A5202 Team. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361:2230-2240.
3. Post FA, Moyle GJ, Stellbrink HJ, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010;55:49-57.
4. Martinez E, Arranz JA, Podzamczer D, et al; BICOMBO Study Team. A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression. J Acquir Immune Defic Syndr. 2009;51:290-297.
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