Hi Joe, This is more a hypothetical question, but one I'm sure is a concern to many, including myself. Why do combo's fail in normally adherent patients with no resistance mutations detected during viremia? Best, and Regards, Michael.

Dear Michael,

Thanks for your post.

Treatment failure in the setting of 100% adherence with no identified resistance before therapy is very rare. When it occurs it can be due to the presence of pre-existing resistant virus that may have been in the mix at a level too low to be picked up by the resistance test (usually less than 10% of the population). When all the susceptible virus get killed off by the drugs these strains grow out.

Other possibilities are the type of treatment chosen...not all combos are equal. For example, a couple of studies looked at the combination of Viread, Epivir and Ziagen together (without anything else)...this combo lead to very rapid failures with resistance. The reason is still not completely known but all 3 drugs share some potential for cross-resistance with one another.

Other possibilities may be drug interactions with other meds that may lower the blood levels of one of the anti-HIV meds, for example use of an acid blocking drug for the stomach that may lower Reyataz levels and compromise activity.

Also, if people have trouble absorbing medication due to gastrointestinal disease or vomiting, that may prevent the meds from being absorbed properly.

It is good that these situations are rare and most people will not have to worry about them.

BEst, Joe