Patients who used abacavir (Ziagen, also in the Epzicom and Trizivir coformulations) as part of their first combination antiretroviral regimen experienced early HIV suppression similar to that of patients taking tenofovir (Viread, also in the Truvada and Atripla coformulations) -- regardless of initial viral load -- and the groups had similar low rates of virological failure at 48 weeks, according to a recent British study.

By Liz Highleyman

Abacavir and tenofovir, 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) widely used as part of first-line antiretroviral therapy (ART), are both generally safe and effective, but some recent research suggested that abacavir might not suppress HIV as well as tenofovir in people with high baseline viral load (>100,000 copies/mL).

As described in the September 1, 2009 Journal of Infectious Diseases, researchers with the UK Collaborative HIV Cohort Study (UK CHIC) analyzed short-term outcomes in all patients who starting ART on or after January 1, 2002, using regimens that included abacavir (73.4%; n = 1136) or tenofovir (26.6%; n = 412), plus lamivudine (3TC; Epivir) or emtricitabine (FTC; Emtriva), plus a NNRTI or protease inhibitor.

In the abacavir and tenofovir arms, respectively, 31.3% and 23.3% had baseline viral load < 30,000 copies/mL, 26.2% and 25.4% had 30,001-100,000 copies/mL, 25.4% and 24.5% had 100,001-300,000 copies/mL, and 25.8% and 18.0% had > 300,000 copies/mL. Compared with patients starting abacavir, those starting tenofovir were more likely to be white (59.4% vs 45.6%, respectively) and to use a protease inhibitor rather than a NNRTI in their initial regimen (30.6% vs 20.9%).

Mean changes in viral load at 2-8 weeks (the first viral load measurement after starting therapy) were calculated using linear regression. Virological failure was defined as having a first viral load > 50 copies/mL during this period.

Results

	Overall, patients starting abacavir experienced a mean viral load decrease of 2.08 log copies/mL over the first 2-8 weeks on ART, compared with a mean decrease of 2.14 log copies/mL among those starting tenofovir.
	There was no significant difference in the week 2-8 changes in viral load between patients who started abacavir and those who started tenofovir, after adjusting for baseline viral load and other factors (difference of 0.03 log copies/mL; P = 0.59).
	Baseline viral load was a strong predictor of HIV RNA decline, but the similarity in response to the 2 drugs did not differ according to pre-treatment viral load level.
	At weeks 24 and 48 after starting ART, there was no significant difference in rates of virological failure between patients taking the 2 drugs (17.9% with abacavir vs 18.4% with tenofovir).

"In these analyses, which are based on a large observational cohort, we found that baseline viral load at HAART initiation was strongly associated with the change in viral load 2-8 weeks after starting HAART," the researchers wrote. However, "no association was found" between NRTI backbone and the change in viral load.

In conclusion, they stated, "our findings indicate that patients with high pre-HAART viral loads who initiate HAART with [abacavir] have short-term viral load reductions comparable to those who initiate HAART with [tenofovir], and this should be taken into consideration when deciding which nucleosides should be used as part of a patient's initial HAART regimen."

University College Medical School, Royal Free Campus, Chelsea and Westminster National Health Service (NHS) Trust, Homerton University Hospital NHS Trust, Medical Research Council Clinical Trials Unit, North Middlesex University Hospital NHS Trust, Department of Virology, University College London, Royal Free NHS Trust, Imperial College Healthcare NHS Trust, Barts and The London NHS Trust, and King's College Hospital, London, UK; Lothian University Hospitals NHS Trust, Edinburgh, UK; Brighton and Sussex University Hospitals NHS Trust, Brighton; North Bristol NHS Trust, Bristol, UK.

8/21/09

Reference
L Bansi, C Sabin, Ri Gilson, and others (for the UK Collaborative HIV Cohort Study). Virological Response to Initial Antiretroviral Regimens Containing Abacavir or Tenofovir. Journal of Infectious Diseases 200(5): 710-714. September 1, 2009.
(Abstract).