The number of salvage patients may be calculated with some current data and assumptions:
450,000 under treatment in the US
Assume: aconservative high estimate of 60 % of patients treated have undetectable viral load (under 50 copies per ml)(from 96 week studies of different drugs)
so, 40 % have over 50 copies per ml
out of those, 13 % have three class resistance (from prior studies)
so around 18,540 patients have 3 class resistance
let’s assume only half of them are in dire need since
their CD4 cells are under 100
So around 9000 are in dire need for new meds. They are
looking not for one, but for three new active agents
to combine
possibilities:
1- TMC 125+ Fuzeon + MK 518+ NRTIs
2- TMC 275+ Fuzeon+ Maraviroc+ NRTIs- probably not as good as (1)
3- Maraviroc + MK 518 + TMC 125 ( all expanded access)
Many of those patients have Fuzeon resistance in 2007. Some of the Fuzeon resistant patients also have resistance to Prezista and Aptivus.
TMC 125 only got 30 % of people undetectable when combined with Fuzeon in a prior 24 week data, so it may not provide much activity for patients with several NNRTI
resistance mutations
The only drug that will truly help most people is MK 518, the integrase inhibitor from Merck,since it is a new class and it is extremely potent. The
secret to its success will be how to add two more active
agents that wil sustain its work effectiveness. 30 % of patients in the Merck BENCHMRK study failed MK 518 after 48 weeks when combined with a background with no active agents. MK 518’s effectiveness increases to about 94% when started with Fuzeon in Fuzeon naive patients. Hopefully, this will be sustained over 96 weeks or more. Resistance to MK 518 will also mean that resistance to the Gilead integrase will be present.
30 % of patients with heavy prior protease resistance
have pre existing resistance to Aptivus and Prezista,
so 30 % of 90000 will be in trouble if they also have
Fuzeon resistance (I am in this group)
Maraviroc will only work for 50% of patients (those
with R5). It is a drug that will help patients in
early stages, not in salvage
So, it is not that simple just to come up with
generalizations about how wonderful it is now to
combine these agents and how there are no patients who need new medications after the Merck integrase is approved.
These assumptions do not include people in Canada, Europe, and the rest of the world.