Two-year data continue to show promise for T-20

In the second year of follow-up, patients injecting the fusion inhibitor enfuvirtide (T-20, Fuzeon) continue to exhibit viral suppression with no new adverse effects, according to data presented today at the Fifteenth International AIDS Conference in Bangkok.

T-20 is the first drug in a new class of ‘fusion inhibitors’ that prevent HIV from entering its target cells. It is given twice daily as a self-administered subcutaneous injection. The TORO study was designed to assess the safety and efficacy of T-20 when added to an optimised background regimen of antiretroviral drugs.

To date, the study has demonstrated that after 48 weeks of treatment, more patients adding the new drug to their regimen have undetectable viral loads and raised CD4 cell counts than those who did not add the drug. Since the patients in the optimised background arm were given the option to switch to the T-20 arm on treatment failure or at the end of 48 weeks in the trial, today’s presentation provided a 96-week update on the patients who were randomised to the T-20 arm. The findings showed that the majority of patients can tolerate the drug for this period, and maintain favourable virological suppression and CD4 cell increases.

Of the 661 patients randomised to receive T-20 at the start of the study, 506 (77%) remained enrolled at week 48, and 368 (56%) at week 96. Using an intent-to-treat analysis, in which discontinuing patients or missing data were counted as failures, the proportion of patients with a viral load of fewer than 400 copies/ml decreased from 37% to 27% between weeks 48 and 96, and the proportion with fewer than 50 copies/ml from 23% to 17%. These values were greater than those at 48 weeks in the patients randomised to the optimal background arm (13% and 8% respectively).

Over the same period, the proportion of patients with a CD4 cell increase of over 50 cells/mm³ from baseline increased from 61% to 76%, and those with an increase of over 200 cells/mm³ from 9% to 37%.

Reasons for patients leaving the trial included injection site reactions (47 patients, 7%), adverse events (81 patients, 12%) and death (6 patients, 1%). It was also reported that 67 patients (10%) left the trial since they had an 'insufficient therapeutic response', with the remainder leaving for administrative reasons, refusing treatment or being lost to follow-up.

When comparing the incidence of adverse events between the first and second years of treatment, the presenter noted that many, including upper respiratory tract infections, fever, diarrhoea, fatigue, joint pain and oral thrush were less common in the second year of treatment.

However, the proportion of patients experiencing injection site reactions – redness and soreness around the injection site – did not decrease across the two years of the study, with 60 to 80% of patients experiencing pain at any one time, although this was mostly mild.

T-20 has been associated with an increased incidence of bacterial pneumonia. In this study, the incidence of pneumonia remained constant at 1 to 2%, significantly greater than in the non-T-20 arm in the first 48 weeks of the study, but without declining in the second year. Dr Keikawus Arastéh, presenting, acknowledged that the reasons for this remain unclear, but he indicated that the drug’s manufacturer, Roche, is investigating this effect, as requested when the product was licensed by the US Food and Drug Administration in 2003.