Sep 26, 2001
I am on triple drug regimen of nevirapine,Lamivudine and stavudine for about 7months;After treatment my cd4 and vl both increases from 230 12000 to 400 17000;I am from northeatern part of India where there is no facilities for doing drug resistance test;With refence to this ,could you suggest a 4th drug that can be added on the current triple drug regimen so that the medicine can be more effective or not prone to drug resistance;Or is it necessary to change to another combination;This present is my 1st combination.
Response from Dr. Young
Thank you for your question.
It is important to try to understand why this might be occuring. I will assume that you are taking your medications faithfully. Less than 5% missed doses can be associated with increased rates of virologic failure. After this issue is considered, then the most common reason for lack of virologic response is viral resistance. I am troubled by the lack of any measured response (though, perhaps there might have been some initial decreases, not measured). This observation could be explained by the presence of drug resistance in your initial virus, though I rather doubt this possibility (even in North American research centers, the rate of primary drug resistance is fairly low). The other possibility (and the one that you bring up) is the liklihood of the emergence of drug resistance on your current therapy.
Resistance patterns after failure of d4T/3TC/NVP typically involve resistance mutations at reverse transcriptase codons 184 or one of the NNRTI-associated codons (103, 181, for example). If you were to remain on this failing regimen for a lengthy period, you could also see the emergence of thymidine-analogue mutations (41, 70, 215 for example). There are two generic approaches to your treatment strategy at this time.
One approach could be to add a fourth agent, to intensify the therapy. We typically use abacavir in this particular setting. This nuke is very potent and has a resistance pattern that overlaps the current therapy (d4T/3TC), hence, there is little negative with regard to engendering additional cross resistance shoudl the approach not be of benefit. When we intenisify therapy, the goal is reduction of viral load to below limit of detection- in a fairly rapid fashion- say within 8-12 weeks, at the most. If this goal is not reached, then I would favor a complete switch of the drug regimen. This approach may not be very likely to work in you situation, given the relatively high viral load (intensification typically works better with lower viral loads) and the duration with which your viral load appears to have been present while on treatment.
If one were to take the approach of switching therapy, then we would like to avoid any of the possible cross resistance patterns of your current treatment. ddI and tenofovir generally have no significant overlap of resistance patterns to d4T and 3TC. Abacavir might also be of some value, if there was no resistance to d4T (implying the lack of thymidine analogue mutations). Since there is some risk of NNRTI resistance; I'd favor switching to a protease inhibitor as the third drug in the regimen.
I hope that this is helpful, good luck, BY
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