A draft update to the 2005 British HIV Association (BHIVA) treatment guidelines is available on the BHIVA website, and any comments should be received by next Monday, September 4th.
The 2006 update is a short summary document updating the full BHIVA treatment guidelines which were published in the July 2005 issue of HIV Medicine.
The guidelines writing committee found that there had been some important new data published since the last guidelines, and so the 2006 update – to be published later this year in HIV Medicine – includes completely rewritten sections on "What to start with" as well as on the new treatment paradigm for treatment-experienced patients.
The remaining sections have been updated with short additional paragraphs summarising the latest data, with no new recommendations.
Nevertheless, some sections may be changed after the September 4th deadline, since important new data, especially regarding "What to start with", have been recently presented at the Sixteenth International AIDS Conference in Toronto.
When to start?
Although some clinicians have felt that data from the SMART treatment interruption study could be interpreted to suggest that individuals should start treatment earlier, the updated BHIVA guidelines say that “no new data have emerged since the previous guidelines to alter the committee’s view that treatment should start before the CD4 cell lymphocyte count has fallen to below 200 cells/mm3, because of the higher risk of death or disease progression in patients who delay starting treatment until their CD4 cell count has fallen to this level, and the reduced efficacy of HAART [highly active antiretroviral therapy] when introduced at a CD4 count of less than 200 in some studies.”
They add that diagnosis of HIV infection before CD4 cell counts reach this level “remains paramount”, and that “this is only likely to be achieved by much more widespread and normalised use of HIV antibody testing.”
What to start with?
The current update begins, “there have been no definitive controlled trials in naive patients to demonstrate the clinical superiority of a HAART regimen containing a currently recommended boosted PI [protease inhibitor] when compared with a regimen containing an NNRTI [non-nucleoside reverse transcriptase inhibitor].” However, recent data presented in Toronto suggest that the NNRTI efavirenz (Sustiva) is more durable over two years than the boosted PI lopinavir (Kaletra).
No changes have been made to the recommended NNRTI, efavirenz, although more details have been included regarding its central nervous system side-effects. “The major side effect of [efavirenz] is dysphoria,” the guidelines state, “which needs to be discussed in detail with the patient prior to commencing the drug. Manifestations include vivid dreams and/or nightmares, sleep and mood disturbance, drowsiness and disorientation. Most are mild-moderate and self-limiting and can be managed with a short course of hypnotics: it is unusual for patients to discontinue the drug for this reason within trials. Nevertheless, in a small minority, symptoms persist and may be severe enough to warrant switch to an alternative agent.”
Nevirapine (Viramune) remains an alternative NNRTI primarily due to concerns related to toxicity.
Kaletra remains the only recommended boosted PI, although recent data suggest that boosted fosamprenavir (Telzir) is equivalent.
Alternative boosted PI regimens recommended by BHIVA include boosted fosamprenavir, boosted saquinavir (Invirase) and boosted atazanavir (Reyataz). Since the latter is still not approved in the EU for treatment-naive individuals, the guidelines suggest that boosted (rather than unboosted) atazanavir should be “restricted to those with established cardiovascular risk factors and where a PI is required.”
Treatment-experienced patients
The guidelines now say that “the goals of treatment for majority of treatment-experienced patients have changed, and the new paradigm should be wherever possible maximal and durable HIV viral suppression leading to immunological improvement with lack of clinical progression and improvement in quality of life.”
Patients with the option of at least two – and preferably three – new active drugs should switch “as soon as possible [after virological failure]…when the CD4 count is higher and viral load lower”. However, the guidelines now recommend that for patients with fewer drug it “may be better to maintain the patient on a failing regimen which maximises the fitness effect and has minimal side-effects.”
The guidelines discuss the recent data on boosted tipranavir (Aptivus) and boosted darunavir (TMC-114, Prezista in the United States where it was approved in June), and suggest that if an individual has never taken enfuvirtide (T-20, Fuzeon) before, they are more likely to achieve an undetectable viral load if they add the fusion inhibitor to a new boosted PI.
For patients who are unable to construct a regimen with at least two new active drugs, the guidelines discuss the latest data regarding switching or remaining on a "failing" regimen, treatment interruptions, 3TC (lamivudine, Epivir) monotherapy, and viral fitness. They add that a strategy that includes incomplete virological suppression can only be considered in the “short term” and “is only relevant until a regimen likely to suppress viral replication completely can be found.”
- The guidelines update can be found on the BHIVA website.
- Comments should be sent via email to editorial@mediscript.ltd.uk by September 4Sth, 2006.
- All comments will be displayed online and reviewed by the BHIVA Guidelines Subcommittee.