Volume 6 Number 11/12 November/December 2005
This double issue of HTB has arrived slightly later than usual in order to include reports from the Lipodystrophy Workshop held in Dublin at the end of November, together with early reports from the EACS conference that followed afterwards. Further reports from these meetings, together with coverage from the rescheduled 45th ICAAC that will now be held from 16-19 December in Washington, will be included in the January 2006 issue of HTB.
In terms of treatment access in the UK, TMC114 is now available on a named-patient programme. Use of either TMC-114 or tipranavir/r, if used with T-20, should offer many people two sensitive drugs. This provides the best opportunity in many years, for viral suppression <50 copies.mL to be a realistic goal for treatment-experienced patients.
Several other reports in this current issue relating to antiretroviral treatments highlight difficulties with the development programmes of pipeline compounds. GSKs CCR5 inhibitor has been shelved, and Phase II trials for Scherings compound in the same class have been stopped in treatment naive patients, though the studies in treatment-experienced patients continue. The decision over the GSK compound was related to hepatic toxicity. So far, this has not so far been seen the other CCR5 inhibitors currently being developed. The Schering decision was based on efficacy. As this issue went to press, Tibotec announced that one of their phase II studies of the NNRTI TMC125 was being stopped early due to poor antiviral efficacy in treatment naive patients, although the Phase III studies are not so far affected, and toxicity issues have not been raised.
In the run up to these Phase II trials, many European treatment advocates, in discussion with the companies and the regulatory agencies, argued that patients with advanced HIV (CD4 count <100-150 cells/mm3) should not be enrolled into trials of investigational agents before efficacy or a dose had been established. The caution was to ensure that patients with more advanced disease are more dependent on achieving an optimal response with their first treatment, and that they should not receive a treatment that was less successful than the minimum standard of care. This was supported by independent investigators and national regulatory agencies in some countries.
It is always very disappointing when unforeseeable problems limit development of promising compounds. In the examples above, the companies developing these drugs appear to have acted swiftly to reduce the risk to patients enrolled in their studies. However, they remain sobering examples of when access to investigational agents is not the same as access to better treatment. For patients with more advanced HIV, many of whom may have been recently diagnosed, and who may be more vulnerable in terms of giving informaed consent for a trial of a new drug, and less aware of the choice of drugs that are already approved, then advocating for greater safety in the earliest Phase II studies appears justified.
To end on an optimistic note, in the US, where ARVs are generally approved six months or so before Europe, there is now a newly approved paediatric formulation of FTC, and approval of the long awaited meltrex formulation of lopinavir/r. Both are covered in this issue.
Finally, as the year draws to a close, we would like to wish all our readers seasonal greetings, and best wishes for 2006.