Dear Dr. Cohen,

I sent you a letter about three months ago but realized you were very busy with the San Francisco conference. Hopefully you will have time to answer my letter now. I am a 51 year old male that tested positive in July 1999. My initial blood work was completed in Sept 1999 with VL of 330,000, t-cell of 434 and cd4 percentage of 27. I had no prior symptoms of any health problems before testing. My doctor has placed me on an initial regimen of three nukes, ziagen and combivir. From some things I have read, I am concerned that this regimen will be strong enough to obtain good results fast enough before resistance and failure might occur predicated upon my high VL. My doctor feels there was no reason to use other types of drugs so early in my initial treatment. I also had a genotype test done recently which indicated I had no resistant HIV strains (I have not seen result of that test). Do you feel three nukes by themselves is sufficient for initial therapy given my numbers, etc. ? If not, what should be added ? I waited as long as I could hoping to hear from you but finally started therapy about three weeks ago with no significant side effects other than the fatigue starting from I assume the AZT side. Please help me and thank you for your wonderful work. Sincerely - Bob

Sorry for the delay Bob. Hope this comes in time to be of use.

There are studies done in those with a baseline viral load over 100,000 like yourself. And on the simple regimen of Combivir/Ziagen there was a reasonable chance of getting the viral load to below 50 copies - our hurdle to a most durable regimen. But there is a somewhat reduced chance of getting there on this combination than on others. The most consistently successful of the three drug combos at high viral loads has been the combination of two nucleosides and a nonnuke - most of the data is with Sustiva/efavirenz, and there is some controversy although some support for how well nevirapine/Viramune might do here as well (with two nucleosides).

However - other combinations can get you there. And you can look at certain timepoints to know if you are "on track" to getting there - meaning in the first 24 weeks, most likely your viral load should be getting close to 50 copies - certainly down towards 400 by then - it can take up to 36 weeks to drop to below 50 copies when starting at a viral load over 300,000. As long as each time you check you are continuing to drop - then this combo can be potent enough for you. It appears to be potent enough for maybe a third of those who take it at this viral load level. And if you do get there - it appears to be durable.

If on the other hand you are not getting towards 50 copies, or bouncing around after being there - there is some interesting info to look at. One school of thought suggests we should do whatever we can to get to below 50 - and so changing this regimen in some way would be needed. The best change to make is unclear - one approach however would be to change at least two drugs if one of them is a nonnuke - like staying on AZT, but stopping the 3TC and abacavir, and going on ddI with a nonnuke. Or keeping the abacavir, and adding ddI and a nonnuke. Or keeping the abacavir, and going on d4T and the nonnuke... get the idea?

That's because if your viral load is not below 50, you likely now have a viral strain that is partially resistant to the 3TC - the most vulnerable drug in your combination. And while you could just add the nonnuke at that point, we have noted in past studies that just adding a nonnuke has occasionally resulted in viral resistance to it as well - adding a single drug like the nonnukes that are "one mutation away" from resistance can sometimes be too easy for HIV to learn how to ignore. So we would change at least two drugs if one is the nonnuke - and since you would not want to be on five meds, and maybe even avoid being on four if you could, one option would be what I mentioned as a way to stay on three.

Hope that clarifies. With any luck you are heading to below 50 and won't need the fine tuning - let me know what happened.

CC