Initiating HIV/AIDS Therapy in Treatment-Naïve Patients What is the role of fixed-dose NRTI combinations?
	Enlarged Version of Graphics Below	Dr. Bellos (OC): We currently have three fixed-dose combinations that we can use... Dr. Bellos (VO): Abacavir and 3TC are now available as Epzicom, and it's once a day. It's a well-tolerated regimen. There are no food restrictions. There is no potential mitochondrial toxicity in this regimen. If one were to initiate a regimen with abacavir and 3TC, there's really no tenofovir cross-resistance... and it has been reported in some of the 3 TC/abacavir trials that you do get a better CD4 cell count response with abacavir on board.   See Slide Dr. Bellos (OC): One of the downsides is the potential for an abacavir hypersensitivity reaction, but I can tell you that in the thousands of prescriptions that I have written for abacavir, I can count on one hand the number of hypersensitivity reactions I've seen where I have actually had to stop the drug, and I think with respect to that, as long as you educate your patient as to what to be aware of with the abacavir hypersensitivity reaction, you can generally decrease the significant incidence of having to discontinue the drug. Most of the patients that-if you look at the data in the trials that have failed, have failed that regimen with the 184V, which is the 3TC mutation, which is, again, not a surprise. Dr. Bellos (VO): The other once-daily fixed-dose combination we have is tenofovir/FTC. It's well tolerated, once daily, no potential associated mitochondrial toxicity. The 184V is still the major mutation that is seen with failure. One of the concerns in that setting is the potential nephrotoxicity of tenofovir, and that is something that we have begun to see a little bit more of as the drug has been increased in use.   See Slide Dr. Bellos (OC): The other issue with that is the hyperpigmentation that can be seen with FTC, although that is not something I've seen in my practice with the use of FTC and the K65R mutation, which is the signature mutation for tenofovir, to provide cross-resistance both to ddI and abacavir, so you have essentially excluded two agents from your armamentarium of nucleoside analogues.   See Slide Dr. Bellos (OC): The third fixed-dose combination is one that has been around for-actually the first one that was probably available, which is Combivir, AZT/3TC. Dr. Bellos (VO): I think the major advantage to Combivir is the fact that there are years of clinical experience with AZT and 3TC. There's prevention of K65 or the L74V mutation with that particular combination. Disadvantages: one, it has to be given twice a day. Unfortunately, AZT does not achieve adequate intracellular concentrations with once-daily administration, and the other thing would be the potential for development of thymidine analogue mutations with long-term use.   See Slide Dr. Kwakwa (OC): It depends on so many parameters as to which of those three combinations is appropriate for a given patient. Sometimes, it depends on what the anchor drug is. With some anchor drugs, drug-to-drug interactions become an issue. Sometimes-and the way I tend to treat today is to come up with a regimen involving the individual medications I would like to start a patient on, and if two of them are available in a co-formulation, then to opt for that formulation for the patient. Dr. Kwakwa (VO): Depending on their comorbidities, depending on their other medications, depending on their schedule, depending on the side effects that they may be willing to tolerate, depending on their total co-burden-to come up with a regimen that delineates the particular chemicals, and then see if there's a co-formulation available.   See Slide Dr. Wohlfeiler (OC): I like the combination of abacavir and 3TC a lot, Epzicom, partly because those are two medications that we have some really long term experience with. They are well tolerated. The risk of hypersensitivity reaction though officially it's out there as being about 8% or so, in my clinical experience it's been more like 2%. So it's not really a problem that I've encountered. So it hasn't been an impediment to me putting patients on that combination. The combination of tenofovir and FTC I think is also a great combination. Though they are two drugs that we have less long-term clinical experience with. I have some concerns about whether there might be some long-term renal toxicity in some patients associated with tenofovir. And though I think that FTC and 3TC are very similar medications, I've certainly heard it raised by some of the PharmDs that I've spoken to about concerns about whether or not the fluoride group on FTC will really lead to some problems down the road. I haven't seen that yet. But we also have less clinical experience with it. So I'm a little more cautious with that combination. Then of course, I still use a lot of Combivir and Trizivir because a lot of good experience with those medications. The only impediment to those is that they are strictly b.i.d. combinations.
Program Menu	Last   |	Next