My doctor and I are thinking of changing regimens from Kaletra/Combivir to Reyataz/Truvada and I wanted a second view from you. In particular, I wanted to confirm that I'm appropriately evaluating the side effects that I might be facing on this new Reyataz/Truvada regimen.

For a little history, I started on Crixivan/Combivir in 2000. I went undetectable almost immediately, with cd4counts ranging from 500 to 700 for 6 years. I have no mutations or resistance to any PI's, NRTI's, or NNRTI's. Further, all other labs were pretty much normal (i.e., triglycerides and total cholesterol around 200, normal kidney/liver). That is, until I started experiencing severe Crixivan crystal sludge in my kidneys in May of this year. That resulted in, what appears to be, temporary kidney damage, with highly-elevated creatinine. After stopping Crixivan, the symptoms resolved, the labs turned back to normal, and I was placed on Kaletra.

The only other "side effects" I experienced under this Crixivan/Combivir regimen were an increasing feeling of anxiousness starting in 2004 that resulted in numerous episodes of tachycardia, where I thought I was having a heart attack. I only experienced this effect shortly after taking my Crixivan (which I had been on for 5 years by then). It might not have been related to Crixivan at all, but I've always wondered whether the piling up of kidney sludge might have been promoting some heartbeat abnormalities. In any case, subsequent stress echos appeared to rule out heart problems with no other high risk factors (no smoking, no family history, no overweight, and relatively normal lipids).

I have responded well to the Kaletra/Combivir regimen, with an undetectable viral load and a cd4 count ranging from 700 to 900. But I have experienced the following difficult side effects.

Consideration of the Kaletra to Reyataz switch is being prompted by continuing GI problems that have not resolved after 5 months on the drug. Further, I have experienced elevated triglycerides that went from 200 to 600 in the first 2 weeks on Kaletra, and have recently skyrocketed to 1,000 (while fasting). Digging a little more into the literature, as well as a call to Abbott, I was somewhat shocked to find that the postmarketing experience is that 30-40% of treatment-experienced patients also have suffered triglycerides over 750!

Given the high level of triglycerides I am experiencing, I have not been too excited about long-term use of another drug like Tricor (which can cause gall stones and pancreatitis) just to counteract the Kaletra--and probably still not achieve "normal" levels, even with a 60-70% reduction in triglycerides that Tricor might achieve. I know that with the Norvir boost, there is no guarantee that my lipids will respond positively to the Reyataz. However, I've seen anecdotal evidence where patients' triclycerides have dropped significantly in just a few weeks after making the switch from Kaletra. Further, if I maintain an undetectable viral load, I have read that perhaps dropping the Norvir boost might be a viable option, which could further increase the potential improvement in my lipid profile. (I realize that this option would be possible only if I ultimately decided to stay on Combivir [or switched to Epzicom instead of Truvada], since Truvada decreases too significantly the level of Reyataz in the blood, thus requiring the Norvir boost).

Consideration of the Combivir to Truvada switch is being prompted by acceleration of facial and limb lipoatrophy that I have experienced since going on Kaletra. Otherwise, however, I've tolerated Combivir very well over these past 7 years, with little or no other side effects of which I currently am aware. I believe the acceleration of lipoatrophy has been prompted by: (1) the severe GI problems I have been experiencing on Kaletra, which includes loss of 5-10 lbs (or 7% of my 150 lb body weight); (2) the complete makeover of my eating habits just to try to find something that lessens the GI effects; and, (3) the change to an extremely low-fat diet to attempt to lessen the adverse lipid impacts. My research suggests that Truvada (unlike Zerit and AZT) is less likely to promote fat loss, and may even permit slow gains back of lost facial and limb fat over time.

The above are the main reasons why I am considering a switch to Reyataz and Truvada. Are these sound reasons for considering a change?

The main concerns I have about adopting a Reyataz/Truvada regimen are the potential "new" side effects I might experience. For Reyataz, my main concerns are 2nd degree AV Block, pancreatitis, elevated bilirubin (which probably doesn't affect liver function), and skin rash (including Stevens Johnson syndrome). How common are these in your experience? If I've had episodes of tachycardia (as described above), should I be concerned about the 2nd degree AV Block?

For Truvada, my main concerns are liver complications, lactic acidosis, bone loss and kidney problems. My labs indicate I've been exposed to HepB, but have never had any liver problems. Does this raise concerns about going on Truvada? Might going off Combivir be a problem--could it exacerbate "dormant" HepB problems?

As for kidney problems, are the potential Truvada effects (tubular compromise, creatinine clearance considerations, I think) more risky since I experienced kidney problems with Crixivan sludge? My current kidney lab numbers are fine. But might I be more susceptible to the potential Truvada effect with my prior Crixivan history?

As for lactic acidosis and bone loss, is Truvada any worse than the other NRTI's? Are these risks that are particularly notable for Truvada?

As a final note, I considered Atripla as an alternative regimen. However, since I've responded well to PI's, I though it might be advisable to stay in this drug class, leaving the NNRTI's for later if I subsequently develop PI resistance problems. Also, I don't believe the literature demonstrates that Sustiva is as lipid neutral as Reyataz, and may, in fact, increase lipids, but perhaps by not as much as Kaletra.

Sorry for the long note, but as time wears on, all these side effects start taking their toll. Since I've seemed to keep the VL down and cd4 improving, I'm now getting increasingly concerned about adopting a long-term regimen with newer drugs that potentially will lessen the long-term impacts. Any suggestions you might have would be greatly appreciated.

You should be commended for doing your homework. In fact, I would agree in general terms with many of the issues you outlined in your post. The problem is that the issues get very complex and there are no definitive answers for many of your questions. I will try to focus some thoughts related many, but possibly not all of your issues. I will do so in such a way that you will hopefully have some additional direction as you move forward.

Based upon what you have written it appears that you are unlikely to have any underlying drug resistance since you report that your viral load has always been undetectable on therapy. This is a critical issue as you move forward so I encourage you to go over your entire treatment history with your provider to verify that this is indeed true. My comments below are all based upon this assumption.

If your viral load has always been undetectable while on therapy then using a NNRTI with dual NRTIs in the next regimen should be a viable option. The lipid effects with NNRTIs are real but modest and I would be hard pressed to say whether it will be better or worse than atazanavir (ATV) with ritonavir (RTV). In addition, NNRTIs are generally less likely to be associated with GI complaints. An important issue to consider with lipids is that usually there are no urgent problems with abnormalities in lipids, except perhaps with very high triglycerides (>1000 mg/dL). It is the long-term consequences that we worry about and this can be dealt with, if it develops with diet, exercise, introduction of lipid lowering therapy or another change in antiretroviral medications. For what it is worth, while you are correct that the lipid lowering therapy can cause side effects, such toxicities are uncommon and most people tolerate these treatments well.

You are correct with regards to ATV toxicity. Unless you had evidence of conduction abnormalities on previous ECGs this should not be a concern for you. The main toxicity is GI, potentially modest lipids changes and the hyperbilirubinemia with approximately 5 out of 100 people complaining of looking yellow. As you suggest, this is not a serious medical problem, mostly cosmetic, and completely reversible when the drug is discontinued. Pancreatitis would be very rare complication of ATV.

Toxicity associated with NRTIs is also complex. Focusing on tenofovir (TDF) since this is the focus of your discussion, the risk of liver damage and lactic acidosis is generally felt to be very low. It is also true that there is some data showing that switching people from D4T or AZT to TDF has been associated with improvements in fat, although the data is much better with switching from D4T than with AZT. The issue of renal and bone toxicity is an area of active research; however, the clinical relevance remains unclear. At this point I would not necessarily worry about this in light of your previous crixivan problems, but you will need to have your renal function followed closely.

Finally, your question about hepatitis B is difficult to assess. I would need to know more about the status of your blood tests. Nevertheless, it is hard to imagine how switching from AZT/3TC to TDF/FTC (Truvada) could be a bad thing with regards to hepatitis B regardless of you infection status.

I hope this helps and I apologize if I missed anything. Best, Eric