My experience with MK 518 and Prezista..and thoughts about TNX 355

Prior to joining Merck’s phase III, my CD4 cells wereon their way down ….from 540 three years ago to 300, then to 200’s and finally to 180 in April 2006.My viral load set point was around 15,000-30,000 for years until April 2006 (VL then = 69,000). I have extensive PI , non nuke and nuke resistance and also failed Fuzeon two years ago. I also had preexisting Aptivus resistance, so I never took that drug.

I had an internal conflict abut making the decision of taking a chance or waiting for later to get two active agents started at the same time. I knew the Tibotec DUET study sucked due to the high probabilities of TMC 125 placebo (50%) and 6 month wait period to get open label drug. Merck’s integrase inhibitor study was a little more friendly with a lower chance of placebo (33%) and a switch to open label after 16 weeks if you fail.

After the activist community was successful in getting Tibotec and Merck to work together, I decided to apply for TMC 114’s (Prezista) expanded access program and at the same time to apply for the last spot on the Merck trial in Texas (in Austin). Getting a drug via expanded access and combining it with another experimental drug in phase III studies had never been done before in HIV.

There was a 33% chance I would get placebo MK518 and go on sequential monotherapy of Prezista with a background of Truvada. My VL dropped to 2000 in a matter of days after I started the study. My Vl dropped to under 50 copies per ml in 3 weeks and stayed there for 24 weeks. I was so happy since I had never had undetectable viral load in 23 years. My CD4 cells went up from 180 to 450 in that period. At week 24, I had what I thought was a blip of 800. Two weeks later it was 20,000. Three months later, I am still at 20,000. My CD 4 cells are now 330 ( a lotbetter than baseline), so I am still benefiting fromthe MK 518+Prezista+ Truvada combo. I also added Reyataz to it in hopes that it would increase the MK518 levels (my VL went down to 2000 after I added Reyataz, but then rebounded a month later)

I have been trying to find out why this happened. I have never had adherence problems at all. But I failed to think about the possibility of Prezista’s preexisting resistance, which may have exposed me to virtual monotherapy of MK 518. With all the hype from Tibotec about their wonder PI, I jumped on their EAP to combine it with MK 518. As you probably know, no resistance test for the study drug is available in EAP’s, so you are always taking a chance if you are taking a drug in an existing class to which you have developed resistance. So, I did not know if Prezista had any activity to my virus at entry. After looking at presented isolate data, it seems that some people with heavy Kaletra resistance can also have baseline resistance to Aptivus and/or Prezista even if they have never taken those drugs. After having Monogram run Prezista’s resistance on my baseline vector at study entry (which had no Prezista resistance info then since the drug was not approved yet), I found out the hard way I am in that “weird”group of difficult to treat patients, as Lew from Tibotec would call us.

Now I am hoping that I my virus is R5 tropic so that I can get access to Maraviroc and that TMC 278 is the super non nuke we hope it will be. And I am also keeping my eyes open for gene therapy. In the meanwhile, I am hoping that M K 518 keeps my virus’ replicating capacity down so that I can live healthy like I have for 24 years without complete viral suppression. With the Panaco’s drug’s bad news, and now TNX 355’s potential termination, I am a little concerned about the pipeline.

About TNX 355….. Most of the patients in the TANOX study had no access to another active agent. TANOX did not allow Fuzeon use either. So, does anyone think that the data on TNX 355 would not have looked better if better OBT’s had been included in the study?I agree with Marty Delaney that this drug may be a horribly expensive to make. But are we sure of that 100%? Would this drug provide good activity when used withMaraviroc, Fuzeon, MK 518 or TMC 278? Can this drug be available via an orphan drug set up? Should this drug be completely dropped? Can a once every two week drug not compete with Fuzeon? Anyway, I am not sure that we have the full picture about this drug and it would be unfortunate to see it dropped. Of course, I have avery strong bias for having this drug move forward ….

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