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Viral resistance and meds
Mar 11, 2001

Dear Dr,

My partner and I have been on AZT and 3TC for about 5 years and seems to have build up resistance to these two meds. Our dr now wants us to use a combo of Viramune, Videx and Zerit, but as we live in South Africa these drugs are extremely expensive and we cannot afford them for both of us.

We decided to take a chance and went of all meds in mid January in order to see whether the virus would loose its resistance against AZT and 3TC. My CD4 count was 59 and my partners count was 180 before we went off the meds. Our very first viral loads was done about two weeks after stopping meds and my VL was 153 000 and my partners was 80 000. We had the VL done 4 weeks later and while both of our counts were quite high, my partners seemed to have gone completely haywire. My VL is now 400 000, but my partner's is 600 000.

How long can we wait to see whether the virus has lost it's resistance against AZT and 3TC? Once we go back on the meds we want to add a third drug to the combo and then see whether this will knock the virus cold.

At present this seems to be our only option, but while we are desperate enough to try drastic measure, we don't want to take too big a risk with our health.

Thanks

Ian, South Africa

Response from Dr. Cohen

This certainly is a tough issue given the resources you have available to you. However, it is gratifying to validate the power of the net to allow us all to be sharing our knowledge across continents.

Here are the issues. What is clear is that AZT and 3TC, even when used together, will only partially control HIV, but HIV can clearly create resistance to these two meds. These meds may stay partially successful - that is why both of your viral loads are increasing after stopping. But your circumstance is one in which stopping prior to a switch is most risky - since a stop in these meds, with an increase in the viral load, has been noted to lead to some loss of CD4 cells. And given where your counts were - there is a risk that illness can happen with this drop.

So - is there any benefit to stopping prior to a switch? We don't know yet, and large studies are underway to try and figure this out. What is clear is that the resistant strains are very likely to always be in us. These resistant strains don't vanish when the meds are stopped - they simply are overgrown by the wild type strains that were controlled by the meds when you are on them. Even so, there may be some small advantage to stopping prior to a switch - by decreasing the amount of these resistant strains that are "floating around". And this may enhance the success of the next combo, assuming that the next combo has some risk of cross resistance with the current combination. And there is a risk of cross resistance when going from AZT/3TC to Zerit/d4T, Videx/ddI, and Viramune/nevirapine. Since AZT mutations can decrease the potency of zerit, and to some extent, to ddI as well.

What to do? Well, it would be most helpful to start a combo that has the best chance of working, while assuming that the treatment interruption does little to help - in other words, don't just assume that you have only sensitive HIV at this point. One approach would be the combo you mentioned - a combo similar to this was used in a study that presented its results last year - using Sustiva instead of Viramune. And the results showed that most did establish suppression - although there was a fall off over time in this success rate, in part due to the risk of neuropathy which can happen when on the d4T and ddI together.

What else to try? Well, if you have never used the protease inhibitors - they remain fully potent for you. One approach worth considering here is the use of a "boosted" PI. This has been studied, and is one way to increase the potency, and sometimes decreases cost as well. For example, just 800 mg of indinavir, combined with 100 mg ritonavir, can be taken twice a day, and can be a very potent option to use - at a price not much higher than any one of the other meds you mention. You might for example consider a boosted PI instead of one of the meds in your combo as a way to improve the potency, if that were an option for you.

Similarly, the use of a dual PI combo, such as 400 mg of both ritonavir and saquinavir has been studied as a foundation for a triple combo, adding just one other med to these two - and the results have been pretty impressive. If you can afford this.

The challenge for you is both economic, of course, but also one of potency and the battle with resistance, and cross resistance in these meds. One approach I would discourage if you can, is to just add one more med and restart the AZT and 3tc. The problem is - based on what your viral load was before you stopped - we just don't have one med potent enough to establish control of HIV. And so whatever single med you add - will only be soon lost to resistance as well. It would be better to substitute something else for at least one if not both of these.

One approach now being studied, which may also be of some help to you, is intermittent treatment. For example, if you cannot afford a year of treatment with an effective combo that does get the viral load suppressed - you may be able to get on a combo that does accomplish this, and then take it less often than every day for the next year - studies are trying "rapid" cycles - such as one week on, then one week off, or longer cycles, such as one month on, and one month off. These cycles can reduce the cost by half, and perhaps allow you to establish even better control of HIV when on meds, losing hopefully little ground in the time off meds. These approaches are only recommended when on something that is working - which is why I mention the more potent options, for you to consider.

It is difficult to know how to advise you - since it is hard to know what options you have available. But the premise is clear - the more potent meds you can start, the more likely they will work. And gain control of HIV. And allow your immune system to regrow.

Hope that helps. Please write back with some follow up. CC



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