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Viral Control and Switch/Stop Rates Similar With ABC/3TC and TDF/FTC in Canada
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Among Canadians starting their first antiretroviral regimen with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC), the regimens did not differ in time to virologic suppression, time to switching or stopping any part of the regimen, or time to switching or stopping ABC/3TC or TDF/FTC [1]. The analysis is limited by its observational nature, but the results tend to support British and European guidelines that recommend either backbone for first-line therapy. US guidelines list ABC/3TC only as an "alternative" option because of a higher failure rate with that combination in people starting therapy with a viral load above 100,000 [2] and because of (inconsistent) evidence tying abacavir to myocardial infarction.
The study involved 442 CANOC cohort members whose first regimen included ABC/3TC and 271 whose first combination included TDF/FTC. CANOC includes adults naive to antiretrovirals before starting their first triple combination after 1999. This analysis focused on people starting ABC/3TC or TDF/FTC with efavirenz, nevirapine, lopinavir/ritonavir, or atazanavir/ritonavir. Everyone had at least two on-treatment viral load results.
The two nucleoside groups did not differ significantly in age, proportion of men, or proportion with a prior AIDS illness or hepatitis C virus (HCV) coinfection. They did differ in (1) province of origin, with British Columbia favoring ABC/3TC and Quebec favoring TDF/FTC, (2) proportion of injection drug users (7.9% with ABC/3TC versus 4.4% with TDF/FTC, P = 0.01), (3) pretreatment CD4 count (210 with ABC/3TC versus 240 with TDF/FTC, P = 0.05), (4) pretreatment viral load (5.0 log with ABC/3TC versus 4.8 log with TDF/FTC, not significant at P = 0.09), (5) proportion taking atazanavir/ritonavir (41.2% with ABC/3TC versus 19.6% with TDF/FTC), and (6) year starting treatment (2006 with ABC/3TC versus 2007 with TDF/FTC, P < 0.001). Overall, then, these differences favor people starting TDF/FTC.
Median follow-up reached 12 months (interquartile range [IQR] 5 to 23) in the ABC/3TC group and 6 months (IQR 4 to 12) in the TDF/FTC arm. Sub-50-copy rates 6 and 12 months after treatment began were 69% and 93% with ABC/3TC and 63% and 89% with TDF/FTC. At the time of this report, 265 people (60%) were still taking their original ABC/3TC regimen and 207 (76.4%) were still taking their original TDF/FTC regimen (P < 0.001).
The multivariate model to pinpoint factors related to time to virologic suppression, time to switch/stop any part of the regimen (for any reason other than virologic failure), and time to switch/stop ABC/3TC or TDF/FTC (for any reason other than virologic failure) considered those two-drug pairs as well as age, gender, pretreatment CD4 count and viral load, third drug in the regimen, injection drug use, HCV coinfection, province, and year starting therapy.
Treatment with ABC/3TC versus TDF/FTC did not influence any of the three virologic suppression or switch/stop outcomes. Beginning therapy with a viral load above versus below 100,000 copies did not affect response rates with the two backbones. Factors independently associated with slower time to virologic suppression were injection drug use and earlier calendar year. Starting treatment with lopinavir/ritonavir, female gender, and later calendar year all favored a longer time to switching or stopping any part of the regimen.
The investigators noted that the CANOC database does not say why people stopped or switched antiretrovirals for reasons other than virologic failure. Other limitations of the analysis are use of both once-daily and twice-daily ABC/3TC dosing and use of both fixed-dose ABC/3TC and separate tablets of the two nucleosides.
References
1. Loutfy M, Raboud J, Tan D, et al. Similar times to virologic suppression and switching or stopping for abacavir (ABC)/3TC and tenofovir (TDF)/FTC in antiretroviral-naive HIV-positive patients starting therapy. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract THLBB208.
2. Sax PE, Tierney C, Collier AC, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361:2230-2240.
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