Further evidence that using T-20 (efuvirtide, Fuzeon) without back-up from other active agents results in significantly reduced chances of virologic suppression was presented on Saturday at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington DC.
The findings are derived from a new analysis of the TORO-1 and 2 studies presented by Dr Cal Cohen of the Clinical Research Initiative of New England, Boston. The TORO studies randomised patients to receive T-20 plus a background regimen optimised by resistance testing or an optimised background regimen alone.
The analysis included 661 patients randomised to receive T-20 and 334 patients who received optimised background.
At baseline patients had an average of 3.9 drugs in their optimised background regimen in the T-20 group and four in the optimised background group. Of these drugs, patients had a mean phenotypic susceptibility score of 1.5 active agents, and a mean genotypic susceptibility score of 1.2 in the T-20 group and 1.1 in the optimised background group.
Genotypic susceptibility scores were assessed again at the time of virologic failure in 189 patients receiving T-20 (52% of all T-20 recipients) and 183 optimised background patients (78%).
In an intent-to-treat analysis which included all patients, those who received an optimised background only were significantly more likely to lose an active agent due to the development of genotypic resistance (22 vs. 10%, p
Approximately half of the patients randomised to optimised background lost at least one of the active agents in their regimen, and the median time to failure of optimised regimens was just six weeks. In contrast the median time to failure in the T-20 group was eight weeks.
Patients in the optimised background who experienced virologic failure were permitted to add T-20 to their regimen, but at week 48 patients in the optimised background group were significantly less likely to have viral load below 400 copies/ml (32 vs. 22%, p
When the analysis was restricted to patients with a baseline GSS of 2 or more, this difference persisted (39 vs. 27%, p
The investigators note, “our results reinforce the concept that regimens that do not maximise the chances of suppression negatively impact future chances of success.”
These findings are likely to raise questions about whether it is appropriate to delay use of T-20 on the grounds that its delivery by injection makes the drug difficult to tolerate. Findings presented at the recent Infectious Diseases Society of America annual meeting show that amongst TORO-1 and TORO-2 participants who received Kaletra and two other active agents in their background regimen, inclusion of T-20 in the regimen resulted in significantly better outcomes. 52% of the T-20 group had viral load below 400 copies/ml at week 48, compared to 27% of the optimised background group (p
Cohen C et al. Selection of non-enfuvirtide (ENF) vs ENF-containing regimens leads to higher failure rates and loss of future antiretroviral treatment options. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, abstract H-580, 2004.
Miralles D et al. Virologic suppression of an active boosted PI regimen is significantly enhanced by the addition of a fusion inhibitor in treatment-experienced patients.42nd Annual Meeting of the Infectious Diseases Society of America, Boston, abstract 921, 2004.