Second Line Therapy with Double P.I.
Dec 1, 2000
For fourteen months, I have been on Combivir and Viracept
with viral load as low as 70. With a viral load rebound to 12,000 and a phenotype test showing resistance to 3TC and Viracept but not significantly to any other drugs, I am
ready to go to a second line therapy. Which combination would you recommend between: Combivir, Videx, Norvir and Crixivan or the same combination but substituting Amprenavir for Crixivan? Also, would you see Zerit being
as effective as Videx? I would appreciate your thoughts on the double Protease Inhibitor approach? Thanks. Gary
Response from Dr. Cohen
Well - here is what we know about switching.
After resistance to Viracept/nelfinavir, tests usually show us that most of the other available protease inhibitors will still be active. That is one of the main attractive features in using this medication in a combination - the ability to have a successful next option. As for which to pick - there is so far no information that allows us to rank order from the available options - we have several to choose from, and each has its pro and con. All should be similarly successful - norvir/ritonavir boosting of any of the other PIs could work here - that includes Crixivan/indinavir, Agenerase/Amprenavir, and Fortovase/saquinavir. In addition, the newest option available at least here in the US is called Kaletra - which has both lopinavir and ritonavir in one capsule. Any of these four combos should be amply potent for you. But in what combination?
After 3TC resistance, we have learned that there is still expected potency from Videx/ddI and Ziagen/abacavir. Either or both of these could be used in this next combination as both should be fully potent still. And since you don't see any resistance to the AZT (one of the two meds in the combivir), AZT could be continued. You could instead switch to Zerit as an alternative - these two have some overlap in how they could be used in this circumstance. And since you have never taken any of the nonnucleosides (nonnuke), that class would also be fully potent for you. So how do we create a new combo?
Well -- basically we would just pick at least 3, if not 4 new meds that would be fully active here, and then choose based on which has the most attractive features, including ease in taking, few expected side effects and so on. It might also help to know your initial CD4 count and pre-treatment viral load as these give us some idea as to the how potent a regimen you need at this point.
But there are many options available for you here. For example - you might combine just ddI, abacavir, and a nonnuke, perhaps adding a fourth med like either Zerit or AZT if you choose to. That triple combination is now in formal study as a follow up to the initial combo you describe. You could also pick any of the dual PI combinations, and add either a nonnuke and/or one or two nucleosides (like abacavir or videx or zerit or AZT). The only combo to avoid is using Combivir with zerit - as the AZT in combivir cannot be combined with d4T/zerit - they are antagonistic in the cells. Many of these can be expected to work quite well for you.
One controversy here is also raised in your question - about continuing the Combivir. This is a combo of AZT and 3TC - and you mention seeing 3TC resistance. There is some controversy about how useful it is to continue the 3TC after resistance has happened to it - there are some useful features to 3TC resistance, but since you can create a fully potent combination without it, you are not "obligated" to continue it at this point.
One last point. Why didn't this initial combo work? You mention your lowest viral load was 70 - and we have learned that when the viral load does not get to below 50 copies, there is a higher risk of viral rebound. So your next combo should be monitored to ensure you do get your viral load below 50 - and consider early intensification if it is not getting there after the first several months on it. But it is worth reflecting if there is any reason that your viral load wasn't fully suppressed. For example, missing doses, or not taking the Viracept with food are ways that decrease the chance for these meds to be fully potent. This is worth noting, only so as to make the next combo as successful as possible. While there can be a third time at bat, the options for doing so successfully get fewer and fewer with each round...
Hope that helps.
Cal Cohen, M.D., M.S.
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