T20 (enfuvirtide) studies presented at Rio

HIV Treatment Bulletin - Vol. 6, No. 9, September 2005
Simon Collins, HIV i-Base

Several interesting studies were presented relating to administration and clinical use of T20.

Julio Montaner from Vancouver reported on plasma levels and injection site reactions (ISRs) using the needle-free Biojector delivery system which administers T20, by pressurised gas forcing the drug through the surface of the skin. [1] The results of a bioequivalence study were reported at the beginning of 2005 and the application to market Biojector for use with T20 is already filed with the FDA, although the system is not yet available outside of trials or compassionate access, both of which are largely in the US. [2]

Twenty-three patients on stable T20 regimens were assessed twice every four weeks prior to switching from the standard needles to the Biojector, and every four weeks thereafter. ISRs were graded from 0-31 to include signs, symptoms, number and duration; and ease of administration was graded from 0 (easy) to 3 (difficult). After a median of 4 weeks (range 1-12 weeks), the median ISR score reduced from 11 (range 5-17) with the needle, to 5 (range 0-11) with the Biojector; and the ease of use scores improved from a median of 1 (range 0-2) to 0 (range 0-0); both p <0.001). Plasma collected pre-dose and one hour post dose showed no significant differences between the needle and Biojector administration at either timepoint.

A significant improvement in tolerability resulting from the Biojector, together with higher rates of achieving undetectable viral load when T20 together with either tipranavir/r or TMC114/r, (see later reports) could considerably broaden use of T20 in treatment experienced patients, as well as improving quality of life for people already on treatment, and is clearly to be welcomed.

A second study from Roche/Trimeris presented results on the use of a smaller gauge, smaller bore needle and reported that this was associated with fewer adverse events and better quality of life. [3] In registrational trials T-20 was given by a 27 gauge, 13mm retractable needle. However, the main side effects of injections site reactions is related to the method of administration and the interaction with the active compound. Use of smaller gauge insulin needles has already been reported by patients to improve ease of administration, and although this study of 100 patients using a 31 gauge, thin-walled, 8mm needle did not include a comparitor arm in patients using the original needles, tolerability and quality of life seemed improved. This may be a useful option for people until the Biojector system becomes widely available.

A study from Gallant and colleagues reported a reduced fear of injections over time, indicated in a retrospective questionnaire that was answered by 158 out of 800 patients who were either using T-20 currently or who had used it in the past (mean duration 16 months, range 1-83 months). Although sustained injection site reactions were also reported in this study, this supports offering T-20 more widely, even when patients have an initial reluctance to use an injectable drug. [4]

Bonjoch and colleagues from Barcelona randomised 17 patients with over 9 months virological suppression on T20-containing regimens to either discontinue T20 (n=7) or maintain treatment (n=10). After 12 weeks, viral load had rebounded in 3/7 of the patients who discontinued T20, compared to none of the patients maintaining T20 treatment. Given that patients were likely to be using T20 because it was one of the few active drugs that they had to choose from, it is unsurprising that almost half the patients rebounded: and perhaps slightly more surprising that 4/7 patients maintained suppression without T20, although follow-up was short. Although T20 has tolerability issues, this small study still suggests that maintaining treatment until an alternative antiretroviral becomes available is preferable, whenever tolerability and quality of life permits. [5]

Two European cohort studies also provided information on the prolonged benefit of T20 in a substantial minority of highly treatment experience patients.

On the 54 patients reported by Bonjoch who started T20-containing regimens in the Spanish cohort, 15% discontinued due to side effects (mainly ISRs). Median follow-up was 11 months (range 3-39), including 12 patients on T20 for over three years. Seventeen patients (31%) achieved sustained undetectable viral load, 7 for >18 months follow-up. Mean CD4 increase was +174 cells/mm³. [6]

Similar results were reported by Elzi and colleagues from 100 patients using T20 that were followed in the Swiss cohort (just under half of whom were in the TORO study). Discontinuation rate was 34%, mainly for ‘patient choice (25%), virological failure (14%) and ARV toxicity (85). Among patients continuing T20 followed after 24, 48, 96 and 144 weeks, 39/54 (72%), 23/38 (60%), 8/13 and 5/10 achieved viral load <400 copies/mL. These patients showed a median CD4 increase of +133 cells/mm³ and +195 cells/mm³ at weeks 48 and 96, although this is observed and not ITT data. [7]

A case study was also presented by Manfredi and colleagues, using T20 in paediatric salvage setting in a highly treatment experienced 15-year old boy who had used over 20 previous regimens. In May 2004, treatment was changed to three drugs with residual antiviral activity (lopinavir/r, ddI, d4T) plus T20. CD4 count and viral load at the change were +35 cells/mm³ and 180,000 copies/mL respectively. After 9 months, clinical symptoms (fever and respiratory, uveitis, low weight) all improved, CD4 count increased to 85 cells/mm³ and viral load was reduced by –1.5 log, to 14,500 copies/mL. [8]

References

Unless stated otherwise, references are to the 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005.

1.	Montaner J et al. Enfuvirtide (T20) plasma levels and injection site reactions (ISRs) using a novel needle-free gas-powered injection system (Biojector) for subcutaneous administration of T20 in treatment-experienced HIV+ patients. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WeFo0205).
2.	Needle-free injections for T-20 in US. HIV Treat Bull. 2005 Apr 6(4).
3.	True A et al. An evaluation of HIV-patient quality of life (QoL) and tolerability after administration of enfuvirtide-based HAART using a smaller needle in a community practice setting. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WePe6.3C09).
4.	Gallant J et al. Change in injection attitudes and patient-reported outcomes among patients with enfuvirtide experience. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WePe12.9C13).
5.	Bonjoch et al. Early viral rebound after enfuvirtide discontinuation in HIV-infected patients on long-lasting viral suppression. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WePe12.3C10).
6.	Bonjoch A et al. Long lasting viral efficacy and safety of enfuvirtide-containing therapy in HIV-1 Spanish infected patients. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WePe12.9C05).
7.	Elzi L et al. High long-term efficacy and safety (144 weeks) of enfuvirtide in heavily pretreated HIV-1 infected patients in the Swiss HIV cohort study. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. WePe12.9C22).
8.	Manfredi R et al. The role of enfuvirtide in multiresistant congenital HIV disease treated since birth. IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: (Abstract No. MoPe9.2C01).

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