The Best Combo?
Aug 21, 2000
I just read an article in POZ Magazine on which drug combo is best when starting treatment.
One doctor from DC suggested starting with two drugs: ddI
and hydroxyurea, because the pill burden and toxicity are lower, it's well tolerated and potent and it maximizes second choices. Patients have done well, most now have viral loads under 1,000; even though the viral load comes down slower.
I thought the goal of therapy was an undetectable VL (under 50). What are the implications of having a VL of 1000? Is a combo of DDI and HU less likely to cause lipodystrophy and other side effects?
Response from Dr. Cohen
Well, part of what makes this field so challenging, difficult, provocative and even exciting is to understand that there are many different conclusions that intelligent, thoughtful clinicians have based on what we have learned so far.
In general you are correct -- the goal of treatment is to maintain a viral load as low as possible -- usually meaning below 50 copies -- in order to provide the longest possible benefit from these medications. This approach has been the best proof so far in maintaining the longest duration of benefit from these meds. Viral suppression to below 50 appears to postpone, for some perhaps indefinitely, the development of viral resistance to these meds for much much longer than combinations which allow some more viral replication. And with viral suppression comes immune restoration. So why the dissent?
Well, there have been a few studies which have used just ddI, and a few which added hydroxyurea to this. One such study has followed a small number of people for a few years, and showed that these few did maintain a viral load of about 1000, and HIV did NOT appear to develop enough resistance to the ddI and stayed suppressed during this time. It turns out that ddI resistance is more difficult to achieve for HIV as compared to how fast it can create resistance to other meds we use. And since the viral load just hovered at this low number -- the CD4 count was stable as well.
And even more intriguing is the idea of immune restoration. When there is maximal suppression, there is very little HIV protein around so the immune system doesn't increase the number of cells directed against HIV. However, in this one study of ddI and hydrea, there was some evidence of an increase in the immune activity directed against HIV -- perhaps because the immune system could "see" HIV each day. And IF this increase in immune activity "works", this would be another way to allow some to eventually stop the antivirals, for some short or longer period of time while allowing the immune system to do the work for us.
So why hasn't this been more widely accepted? Well, for one, there is mainly only one small study of this combination that went longer than a year, and large scale recommendations are based on much larger studies. So for many experts, this study needs to be done again to be considered useful as a treatment option. Second, is that there are potential downsides to this approach, including the risks of these two medications. In addition, it is likely that some will not stay suppressed -- it is not likely to be potent enough for those with lower (below 200 or so?) T4 counts, or higher viral loads ("higher" might be anyone above perhaps 50 thousand or so). As for the risk of lipodystrophy, it is difficult to know since so few have been on this combo for long enough. But since there is no PI in this combo, there wouldn't be any PI associated side effects... Finally there is some risk of resistance still -- given the ongoing viral replication. And there are very rare cases of ddI resistance leading to viruses that are difficult to control with the other meds in this class... although it is fair to point out that triple therapy can also result in resistance.
So as with all treatment decisions -- you must decide how much information you and your clinician need in order to choose what YOU would do. Since there is not enough information on this combo, you might consider seeing if there is a study of this available to you as there might be studies underway which are exploring this combination, or ones similar to it. Since research is the only way that we'd be able to more fully answer your important question...
Hope that helps.
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