Initiating HIV/AIDS Therapy in Treatment-Naïve Patients What about using other nucleosides?
	Enlarged Version of Graphics Below	Dr. Kwakwa (OC): Well, 3TC also remains a very important nucleoside going forward, partly because it is so incredibly well tolerated with very limited toxicities, and partly because when resistance to 3TC does occur, it is in the form of the M184V mutation which, while no mutation is good, has been associated with some benefit for the virus-benefit for us, not for the virus-for the person infected. Dr. Kwakwa (VO): Another importance of having 3TC as part of a regimen is as the weak point of the regimen, if you will, in the sense that resistance tends to occur to 3TC first when it begins to occur to the regimen-is that the 3TC resistance, the 3TC mutation, then serves as a sentinel mutation to warn us, or to prepare us to make changes, if you will, and of course, the other issue with the M184V mutation also is that it provides some hypersusceptibility benefits to some of the other agents such as zidovudine, to a lesser extent stavudine, and to some extent as well, tenofovir.   See Slide Dr. Bellos (OC): Two other things that have been talked about to some degree with respect to zidovudine has been the hematologic toxicity, which is honestly something that we have not seen in our practice. I think in the early days-I've been taking care of patients since 1981, and we first started using AZT in 1987, '86. Then, we saw significant issues with hematologic toxicities, but we were dosing it at 1200 mg a day, instead of our current dosing regimen. And there can be the potential, simply because it is a thymidine analogue, for some mitochondrial toxicity, so you can expect to see some of the lipodystrophy, lipoatrophies, and possibly some of the hyperlipidemias, or hyperlactemias that you can see with the other thymidine analogues. Dr. Kwakwa (OC): Anemia is always a concern when beginning therapy with zidovudine. It's not a frequent occurrence on the medication, and it certainly is nowhere near as frequent as it was many years ago, when we were using much higher doses of AZT, but it certainly can occur, and so, it is one of the laboratory parameters that should be monitored whenever we start patients on a zidovudine-containing regimen. Dr. Wohlfeiler (OC): I think that the potential nephrotoxicity with tenofovir might be underestimated at this point. And I could be wrong. But I have seen some studies that have raised concerns that maybe we are under identifying nephrotoxicity associated with the drug. And I've worried too that it may be an ongoing problem that we'll see more the longer people have been on the medication. Certainly it's quite clear that anybody's who's got any underlying preexisting renal problems, probably those are going to blossom when tenofovir is added into the mix. So I certainly use a lot of it, but I'm cautious and I'm a little more careful about using it than I have been. And I'm starting to monitor patients in different ways by calculating out things like glomerular filtration rate instead of just looking at serum creatinines, which I think may not be sensitive enough to pick up early renal toxicity. Dr. Bellos (OC): We are now seeing patients with a whole different set of comorbidities, and that in making our initial choices, or even our secondary choices for regimens, those comorbidities need to be taken into account, so consistent with the nucleoside, one of the issues that we have, for example, in patients with renal failure-I see a fair number and care for a fair number of patients with renal failure on dialysis. For example, the fixed-dose combinations in those particular patients are not particularly helpful, because we cannot adjust those nucleosides in the fixed-dose combinations for the patients' creatinine clearance, so one, again, has to take that into account when one is making a decision about what nucleosides to begin with. Are there certain nucleosides that have a higher potential for nephrotoxicity? Dr. Bellos (VO): Recently, the IDSA published guidelines looking at renal disease in HIV-impacted patients, and their recommendations are that patients actually get a dipstick urine at the time of their initial presentation looking for proteinuria, and if there's any proteinuria, one needs to proceed with further workup, again assuming that the comorbidities in these patients may actually make some of the underlying renal issues or lipid issues even worse.   See Slide
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