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Some Lipids Improve With Switch From
ABC/3TC to TDF/FTC, HIV Control Rates Similar
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51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
Lipid profiles improved in people who switched from abacavir/lamivudine (ABC/3TC) to tenofovir/emtricitabine (TDF/FTC) while maintaining a ritonavir-boosted protease inhibitor (PI) in the randomized SWIFT trial [1]. Similar proportions making the switch and maintaining ABC/3TC kept their viral load below 50 copies, but a higher proportion maintaining ABC/3TC had a virologic failure in this multicenter US study.
Previous trials found virologic and/or safety advantages in starting antiretroviral therapy with TDF/FTC rather than ABC/3TC [2,3], although a nonrandomized Canadian cohort study found equivalent virologic response rates with the two double-drug formulations in initial regimens [4].
To assess the impact of switching from an HIV-suppressive ABC/3TC regimen to TDF/FTC, SWIFT study researchers randomized 311 people with a viral load below 200 copies for at least 3 months while taking ABC/3TC plus a boosted PI to maintain that combination or to swap ABC/3TC for TDF/FTC. No one had a history of resistance to any study drugs, and participants could have any CD4 count.
Clinical characteristics did not differ substantially between the two study arms: 85% were men, 28% were African American, and 72% had comorbidities. Median age stood at 46 years and median CD4 count at 532. About half in the ABC/3TC group (51%) were taking lipid-modifying drugs, compared with 43% in the TDF/FTC group.
After 48 weeks of treatment, a time-to-loss-of-virologic-response analysis determined that 86.5% who switched to TDF/FTC and 83.3% who stayed with ABC/3TC still had a viral load below 200 copies. The treatment difference of 3.1% (95% confidence interval -5% to +11%) meant that changing to TDF/FTC was virologically noninferior to staying with ABC/3TC. A significantly higher proportion maintaining ABC/3TC than switching to TDF/FTC had a study-defined virologic failure (7% versus 2%, P = 0.034), but low-level viremia accounted for most of these failures.
Three people (2%) randomized ABC/3TC arm dropped out of the study because of adverse events, compared with 7 (5%) randomized TDF/FTC arm. One person in each group dropped out because of kidney problems. Grade 3 or 4 adverse events rates were similar with ABC/3TC (10%) and TDF/FTC (8%). One person taking TDF/FTC and none taking ABC/3TC 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.
At week 48 certain median lipid readings favored the switch to TDF/FTC over staying with ABC/3TC, while median decline in estimated glomerular filtration rate (GFR) was greater (worse) with TDF/FTC:
-- Fasting low-density lipoprotein cholesterol: -7 vs +2 mg/dL, P = 0.007
-- Fasting total cholesterol: -21 vs -3 mg/dL, P < 0.001
-- Fasting triglycerides: -18 vs. -9 mg/dL, P = 0.074
-- Estimated GFR (Cockcroft-Gault): -8.3 vs -4.5 mL/min, P = 0.012
"Good" high-density lipoprotein (HDL) cholesterol did not change much in either arm through 48 weeks. And the important total-to-HDL ratio did not differ significantly between study arms through 48 weeks. In the TDF/FTC group, the proportion of people with triglycerides above 200 mg/dL fell from 42% at the switch to 29% at week 48. In the ABC/3TC group, proportions with triglycerides above 200 mg/dL remained stable from week 0 to week 48 (39% and 42%).
At the 48-week point, change in 10-year Framingham cardiovascular risk score did not differ between the TDF/FTC group and the ABC/3TC group; nor did change in 2-year Framingham score in people who entered the trial with a cardiovascular "event."
References
1. Campo R, DeJesus E, Khanlou H, et al. SWIFT study: switching from lamivudine/abacavir (3TC/ABC) to emtricitabine/ tenofovir DF (FTC/TDF) based regimen improves lipid parameters while maintaining virologic suppression. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H2-786.
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. Tan DHS, Chan K, Raboud J, for the CANOC Collaboration. Comparison of abacavir/lamivudine and tenofovir/emtricitabine among treatment-naive HIV-infected patients initiating therapy. JAIDS. 2011;58:38-46.
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