Epzicom versus Truvada in Combination with Lopinavir/ritonavir (Kaletra): Results from the HEAT Trial

Both Epzicom and Truvada are widely used as a NRTI backbone in combination with protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) for therapy in treatment-naive HIV patients.

Final results of the HEAT trial (Head-to-head Epzicom and Truvada), comparing the 2 coformulations combined with lopinavir/ritonavir, were published in the June 23, 2009 online issue of AIDS.

HEAT enrolled 688 treatment-naive patients, of whom 82% were men and 36% were black. Participants were randomized to receive a once-daily regimen of either abacavir/lamivudine 600 mg/300 mg or tenofovir/emtricitabine 300 mg/200 mg, both in combination with lopinavir/ritonavir 800 mg/200 mg.

Participants were not screened for HLA-B*5701, a genetic test that shows which patients are at risk for abacavir hypersensitivity reactions.

Primary endpoints were the proportion of patients with HIV RNA levels below 50 copies/mL at week 48 (missing = failure) and the proportion experiencing adverse events over 96 weeks.

Results

	68% of participants in the abacavir/lamivudine group vs. 67% in the tenofovir/emtricitabine group achieved HIV RNA below 50 copies/mL.
	This demonstrated the non-inferiority of abacavir/lamivudine to tenofovir/emtricitabine at week 48.
	Non-inferiority of the 2 regimens was sustained at week 96 (60% vs. 58%, respectively);
	Efficacy of the 2 regimens was similar in patients with baseline HIV RNA ? 100 000 copies/ml or CD4 counts below 50 cells/mm3.
	By week 96, the median CD4 cell increase was 250 cell/mm3 in the abacavir/lamivudine arm vs. 247 cells/mm3 in the tenofovir/emtricitabine arm.
	Early study discontinuation due to adverse events occurred in 6% of patients in both groups.
	Protocol-defined virological failure occurred in 14% of patients in both groups.

Based on these findings, the authors of the HEAT trial concluded, "Both [abacavir/lamivudine] and [tenofovir/emtricitabine] provided comparable antiviral efficacy, safety, and tolerability when each was combined with lopinavir/ritonavir in treatment-naive patients."

End of summary of HEAT trial published in June 23, 2009 issue of AIDS.

Other HEAT coverage on HIVandHepatitis.com - Results Differ in HEAT trial and ACTG (AIDS Clinical Trials Group) Study 5202

Following are excerpts from a press release on publication of the HEAT trial findings from GlaxoSmithKline, the manufacturer of Epzicom (abacavir/lamivudine):

About Abacavir (Ziagen) and Hypersensitivity

Abacavir sulfate (abacavir) is a nucleoside reverse transcriptase inhibitor with an established safety and efficacy profile in HIV treatment. Abacavir is a component in the GSK products Ziagen, Trizivir and Epzicom.

The most significant treatment-limiting event known to occur with abacavir is a hypersensitivity reaction, which occurs in approximately eight percent of patients and usually emerges within the first six weeks of therapy.

Symptoms of a hypersensitivity reaction to abacavir include combinations of at least two of the following: fever, rash, constitutional symptoms, gastrointestinal symptoms and respiratory symptoms that become more severe with continued dosing and may become potentially life-threatening. These symptoms may overlap with adverse events related to other HIV medications and other medical conditions, contributing to difficulty in diagnosis on the basis of symptoms alone.

Results from HLA-B*5701 testing to assess risk for abacavir hypersensitivity reaction should never substitute for appropriate clinical vigilance for abacavir hypersensitivity reaction and patient management in individuals undergoing treatment with abacavir-containing products.

About HLA-B*5701 Screening

	HLA-B*5701 screening should be performed in patients without prior abacavir exposure.
	It is important to discontinue abacavir permanently if hypersensitivity cannot be ruled out, regardless of the result of the HLA-B*5701 testing.
	HLA-B*5701 testing should never be performed to support a decision to re-challenge with abacavir.
	HLA-B*5701 screening for the risk of abacavir hypersensitivity should never substitute for appropriate clinical vigilance and patient management in individuals undergoing treatment with abacavir-containing products.
	Skin patch testing was a research tool used in this study to detect an immunologic skin reaction to abacavir. Its utility in clinical practice, however, has not been established.

6/23/09

Reference

DH Sutherland-Phillips, H Denise, C Vavro, and others (for the HEAT study group). Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. June 23, 2009 (Epub ahead of print).

Other Source

GlaxoSmithKline. Head-to-head 96-week study shows Epzicom was comparable to Truvada -- in efficacy and safety measures -- for HIV treatment-naive patients. Press Release. June 23, 2009

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