I need advice on a possible med change

[whizzer]

Hey guys,

I need some help making a decision.

I started my first combo of Truvada, Invirase, Norvir and Fuzeon on 31 JAN 06.  My numbers at that time were VL=60,000, CD4=262, CD4 percent=11.  On 26 JUN 06, my numbers were VL=159, CD4=848, CD4 percent=25.  The viral load dropped a lot at first but has tapered off and is dropping very slowly since then (on 19 MAY 06, my VL=288).  I have had virtually NO side effects at all on the current combo, except for the occasional injection site rxn from the Fuzeon.  I did have Immune Reconstitution Syndrome (well, thats what they THINK it might have been, I was sick as a dog) in April, when my WBCs jumped to 20,000 and my CD4s went to 1478, VL at that time was 1049.

I am in a drug study, hence the Fuzeon in my first combo.  The study wants the VL to be undetectable at 24 weeks (which will be on the 17th of July, but can be plus 4 weeks if need be.  Any meds except Fuzeon can be changed in this study.

My doc is not concerned, but of course we want to get the VL to be <50 as soon as possible.  He said perhaps a change of Protease Inhibitor might do that.  He suggested possibly switching to Kaletra.  My lipids are normal and have never been a problem for me, but I am concerned about the possibility of lipid effects with Kaletra.

I was wondering about Reyataz/Norvir as a PI.  I know there is a risk of kidney issues with the Truvada and Reyataz, but my kidney tests are, and always have been, normal.

My resistance profile shows PI mutations 35D, 60E, 63P, and 77I.  Resistance analysis shows maximal response for Kaletra, maximal response for Invirase, and susceptible for Reyataz.  I can give you numbers for fold change and cut-off if you think they would be helpful, but I don't know what they really mean.

So the choices are:

1)  Continue the Truavada/Invirase/Norvir/Fuzeon and hope VL continues to drop

2)  Swich to Truvada/Kaletra/Fuzeon

3)  Switch to Truvada/Reyataz/Norvir/Fuzeon

4)  Do another viral load test at the end of this month and then decide

What are your thoughts?  What are the pros/cons of Truvada/Kaletra vs Truvada/Reyataz/Norvir?

I appreciate any insight you can give.

THANKS,
Whizzer

[newt]

With your PI mutations there is prob. nothing to choose on paper between the Kaletra and the Reyataz, other than the Reyataz being kinder to lipids. Either would be good. 

(Kaletra prob gives the doc a better emotional sense of security cos its older and more studied but several studies eg as reported here show boosted Reyataz = Kaltetra in terms of effectiveness in treatment-experienced patients).

Both boosted Reyataz and Kaletra are a little stronger the Invirase (perhaps a 0.3 log extra reduction in VL on average at 26 weeks).

Changing the Truvada for Viread (tenofovir) + Ziagen (abacavir) would also add a little extra strength and this may be enough to kick the VL to under 50.  In this case I would go the Kaletra route, because there are studies that support this combination as effective (but in truth boosted Reyataz will prob be viable here too).  Some people consider Viread/Ziagen off-piste though.

I would ask for a VL test by another lab.

Do you have any nuke resistance?

- matt

[whizzer]

Thanks Matt,

NRTI/NtRTI mutations 211K, 333E.  Maximal response (Retrovir, Epivir, Videx, Zerit, and Viread) or susceptible (Hivid, Ziagen, and Emtriva) to all meds in this class.

[gerry]

Whizzer:

Regarding those mutations (both PI and NRTI/NNRTI mutations), it doesn't look like any of them have any bearing on the antiretroviral options (i.e., none of them are due to selective drug pressures so they should not play a role on drug resistance by themselves).

Regarding lipid abnormalities, I don't believe the risk would be substantially different for Kaletra compared to the Invirase/Norvir that you are already taking.  Both combos are known to affect lipids.  Reyataz/Norvir is, as you said, an option that would likely not pose this problem. 

What exactly would happen with your participation in the trial if your VL is still above 50 in case you decide to wait another few weeks?

Gerry

[lydgate]

Whizzer,

Apart from the Fuzeon, were the other drugs selected for you by your doc or did you select them yourself (in consulatation with him/her of course)? Just curious why Invirase/Norvir was chosen over the two alternative PIs you're now thinking of. If the resistance testing was done before the study started (I'm assuming it was), and Kaletra showed "maximal response" as well as Invirase, then I'm mildly surprised why K. wasn't chosen (after all, it's the "preferred" PI and all that). Was it a lipid issue right from the start?

My personal preference (and this is not a medical opinion) would be for Reyataz/Norvir. First, the qd dosing (you're no longer treatment-naive so Kaletra would be bid). Second, the GI issues -- Reyataz more "benign" when it comes to diarrhoea etc. And third, the lipid thing of course (and all the implications that may have for long-term lipo side-effects).

Jay