|"Duo"( only 2 drug therapy)??
Jun 22, 2005
I'm wondering if you or other clinicians are seeing other "long term" patients going back to any "duo drug" therapies" with success in viral control & CD4 count maintance??
I have been through most classes of the antiviral drugs over the past 9 plus years having gone from "azt" only to Combivir to various 3 or 4 drug combos.
I have had to stop combinations because of GI side effects; sleep disturbances, neuropathies, and viral load control "failures"/ resistance.
Last November I stopped my Viramune due to suspected GI problems. I had been on Viramue, Epivir(3tc), and Viread for over 2 yrs. My viral loads had been below 50 (undectable) on a consistant basis, and my CD4 counts have ranged from the mid-500's to nearly 1,000 over those 2+ yrs.
After stopping the Viramune,my GI problems improved( I had been having sever gastric reflux pain with no other identifiable source/s).) I have remained on only the Epivir and Viread since early last November.
Since being on only those 2 drugs my viral loads have been less than 50(undectable), but my CD4 count has varied from the mid 500's before stopping the Viramune, to a low of 435(near my lowest level ever)in March-- back to over 900 now(June).
Are ID docs/ HIV specialists seeing other HIVers on any similar 2 drug combo with such good results in the era of 3 or 4 or more drug combos? ---Or, am I just an "odd" case???
My current doc. says "it's unconventional", but we both are saying "if it's not broke, don't fix it" at this time.
Signed, Wondering in the Midwest
Response from Dr. Sherer
Yes, you are odd case, though many HIV physicians have rare patients who seem to maintain suppression with less than optimal therapy, i.e. two drugs compared to three. As this is only 6 months with this response, I also would note that it is still unfortunately most likely that this regimen will not maintain virologic suppression.
I would not recommend that readers of this page look to this option as a possible solution without great skepticism - most patients who experience a prolonged episode of two drug therapy will develop virologic failure, declining CD4 cells, and drug resistance.
We know from the early days that two NRTIs can be successful for prolonged periods of time in people with very mild HIV disease, relatively higher CD4 cells, and initial viral loads below 10,000. This was a minority of those patients; most developed drug resistance and virologic failure after an average of 1-3 years. You didn't mention your baseline numbers - this might be playing a role.
The problem is that 2 NRTIs are not nearly as potent as three drug therapy, both at bringing down the viral load with initial treatment, and at maintaining suppression. That is particularly likely to be true in your case, as you were initially treated with monotherapy and dual therapy, and are likely to have some NRTI resistance mutations. It would also be helfful and of interest to take your past genotype test results into consideration here.
The concept that maybe we could use potent 3 drug therapy until viral control was established, and then 'de-intensify' to one or two drugs - was enthusiastically tested in three studies early in the HAART therapy - and in each case the 1 or 2 drug regimens were inferior to maintaining full suppression by a wide margin. It should be noted that a minority of patients on the lesser regimens did suppress. And it also should be noted that the regimens tested were from the early HAART era, i.e. AZT+3TC+IDV followed by AZT+3TC or IDV alone.
With the newer agents such as boosted PIs like lopinavir/r (Kaletra) and the newer NRTIs such as abacavir and tenofovir, there is again some interest in the strategy....but all should understand that it remains an interesting idea that has yet to be proven. One strategy under study is full 3 drug therapy with lopinavir/r followed by lopinavir/r alone when control is well established. There are some reasons to believe that the boosted PIs may offer an advantage in the strategy.
Finally, there is good evidence - in patients who are resistant to most or all classes and drugs, and who, like yourself, have had significant toxicity to many drugs - that there can be benefit to maintaining a less than optimal regimen in an effort to impair the 'fitness' of the virus. Again, these are preliminary studies, but it appears that the NRTIs are well-suited for this purpose, while the NNRTIs and the PIs appear to be of less value.
SO I'm not willing to take any major lessons from your situation, other than that we can't always explain or predict what will happen in a given patient, and we are well aware that our treatment recommendations are based on clinical trials and guided by the experience of the majority of participants in the trial. Most clinicians have experience with unusual exceptions, and yours, so far, appears to be one.
And of course this is a 6 months 'test' of this strategy. The real outcome is yet to be seen. I would continue this dialogue with your physician and maintain close follow up. So far, so good.
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