The 3TC-like compound FTC (emtricitabine) has out-performed d4T in a study comparing the two nucleoside analogues in treatment-naïve individuals. New data from a company-sponsored study, FTC-301, were reported at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy in San Diego today.
FTC-301 was a randomised, double-blinded study comparing FTC with d4T in people new to HIV treatment. All participants received open-label enteric-coated ddI plus efavirenz in addition to their allocated therapy. The study was closed early after a planned analysis at 24 weeks noted a clear benefit in those receiving FTC (as reported here on aidsmap.com).
FTC-301 was open to people with viral loads between 5,000 and 100,000 copies. Five hundred and seventy-one people were recruited. At baseline, median viral load was 4.9 log copies (just below 100,000), and median CD4 count was approximately 300 cells.
After 24 weeks, virological failure (defined as viral load above 400 copies at week 12, or any rebound above this level) occurred in 10% of d4T recipients versus 4% of those on FTC. Efficacy failure, whether virological, or due to tolerability, disease progression or loss to follow-up, was seen in 13% versus 7% respectively. Comparing rates of virological suppression by intent-to-treat noncompleter equals failure analysis, 79% of the d4T arm reached below 400 copies at week 24, versus 87% of the FTC arm. Seventy per cent and 81% respectively went below the 50 copy mark. CD4 counts rose an average of 152 cells in those receiving FTC versus 122 cells in the d4T arm. All of these differences are significant.
Participants allocated to d4T were more likely to report diarrhoea, nausea and abnormal dreams than those receiving FTC. Why this latter problem, a recognised side-effect of efavirenz therapy, should have occurred more frequently in the d4T arm is not clear.
Clinical lactic acidosis occurred in three people receiving d4T. There were no cases in the FTC arm. Other than this, there were no differences in lab abnormalities. Lactic acidosis is one of several side-effects which are the result of mitochondrial toxicity related to the use of drugs in the nucleoside analogue class. Following a series of negative reports on d4T at the HIV Lipodystrophy Workshop (reported on aidsmap.com over the last few days), a second study presented at ICAAC today reported a comparatively greater risk of mitochondrial damage in d4T users than those receiving another NRTI. Click here to read this story.
FTC is dosed once daily. It is not licensed anywhere at present.
Saag M et al. A randomized, double-blind, multicentre comparison of emtricitabine qd to stavudine bid. 42nd ICAAC, San Diego, September 27-30, 2002, abstract LB-1.