July 2007

Hot Topics Presented at 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention

Contributed by: Heather Huentelman, PharmD, BCPS

Epzicom ® versus Truvada ®: Are they equal?

Abacavir/lamivudine (ABC/3TC or Epzicom ®) was compared head-to-head with Truvada tenofovir/emtricitabine (TDF/FTC or Truvada ®) in 333 patients with viral loads less than 200 HIV-1 RNA copies/mL. 1 Both Epzicom ® and Truvada ® are a one pill once a day combination of nucleoside reverse transcriptase inhibitors. Epzicom ® is know for the abacavir-hypersensitivity reaction that requires discontinuation of the medication and can not be rechallenged. Truvada is known for causing potential renal insufficiency. Both combinations are thought to be very effective in treating HIV, and are most different based on their side effect profiles.

• 13.3% of TDF/FTC patients failed treatment compared to 19.2% in the ABC/3TC group
• ABC/3TC did not meet non-inferiority criteria
• Intent-to-treat: switching= failure
• Secondary endpoint of rates of virologic failure were similarly low 2.4% ABC/3TC versus 0% TDF/FTC
• Discontinuation were higher for ABC/3TC 10% versus 5% TDF/FTC (P=0.004)
• HLA-B*5701 was found in 3 of the 9 patients with suspected ABC hypersensitivity
• No difference in renal function or bone mineral density
• Median CD4+ cell count increased by 44 cells/mm3 for ABC/3TC and decreased by 2.7 cells/mm3 for TDF/FTC (P=0.032)
• Study did not receive any commercial support and the authors report no relevant financial relationships

Summary

I find this to be a very interesting study; it demonstrates to me that Epzicom ® works as well as Truvada ® as long as the patient can tolerate the medication. Screening for abacavir hypersensitivity is a very important factor to continuation of the medication (i.e. determine the absence of the HLA-B*5701 allele prior to starting any abacavir containing regimen). It was also striking that there was an increase of 44 CD4+ cells/mm 3 in the Epzicom ® arm. There may be less mitochondrial toxicity associated with Epzicom ® leading to increased T-cell counts. This may not be a big factor for patients with high CD4+ cells but could mean the difference between requiring prophylaxis and not in patients with low CD4+ cells (near 200 cells/mm 3). It is also interesting to remember that when comparing tenofovir/emtricitabine to zidovudine/lamivudine that was a higher CD4 cell count for the TDF/FTC group. 2,3 This might mean that Epzicom ®>Truvada ®>Combivir ® for increasing overall CD4+ cell counts. It would be interesting to have a study comparing all three combinations with presence of the HLA-B*5701 allele as an exclusion criteria.

1. 4 th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention: Abstract WESS102, Presented July 25, 2007
2. Gallant JE, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006 Jan 19; 354(3):251-60.
3. Pozniak , AL et al . Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic changes--a 96-week analysis. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):535-40.

TMC278 may be superior to efavirenz with by reducing common side effects including CNS and metabolic effects

TMC278 is a new agent in the non-nucleoside reverse transcriptase class by Tibotec. TMC278 has been compared to efavirenz (Sustiva ®) in a phase 2b C204 study with 368 ART-naïve HIV-1 infected patients.

• 33% of patients receiving TMC278 experienced CNS side effects of headaches, dizziness, and somnolence while 53% of patients receiving efavirenz experience CNS events (P=0.002)
• Psychiatric disorders (insomnia, depression, nightmares and unusual dreams were comparable between the two groups
• 13% TMC278 vs. 16% EFV
• TMC278 may have a better metabolic profile
• Lower mean changes from baseline for total cholesterol, LDL and triglycerides (p<0.001)
• The authors conclusions were that TMC278 improves safety and tolerability while maintaining the low pill burden of one pill once a day
• Results will be further explored in phase 3 trials

TMC125 is another new agent in the same class with an excellent safety profile. Both agents will have an impact on ARV-treatment naïve patients. With all the new agents in the non-nucleoside class, tolerability, safety and resistance profiles will determine the agents place in treatment.

4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention: Abstract TUAB105, presented July 24, 2007; abstract WEPEA 105, presented July 25, 2007

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