About 2%-4% patients fail the first line therapy every year in India, mostly related to adherence issues. Testing shows them to have resistance to the NRTIs and NNRTIs. Would it be acceptable to start a 2 drug regimen of Raltegravir with Darunavir/rit or Lopinavir/rit in them or should one add a third drug (say Tenofovir or lamivudine or emtricitabine) ignoring the resistance pattern.
If there is a anti-HIV drug resistance test result available which shows resistance to all NRTIs and NNRTIs, then the option available would be to use a boosted PI like Lopinavir/Ritonavir combination with an integrase inhibitor like Raltegravir.
Srikanth Tripathy
Dear Sir,
Nice to interact with you here.
The reason for the question was that studies like ACTG 5262 and NEAT that looked at the 2 drug combination of DRV/r+RAL showed poor performance at high Viral load and low CD4 counts. Many of our patients with drug failures fall in this category. The resistance pattern for Tenofovir and Lamivudine/Emtricitabine may range from intermediate resistance to complete resistance.
I was wondering if despite invitro resistance pattern, addition might be beneficial "in vivo" by providing the third pillar.
regards
Even with full blown resistance to lamivudine or emtricitabine (for example, in the presence of M184V mutation), the use of one of these NRTI is advised since it is a way to diminish HIV replicative fitness, as you can see in Turner, Clin Diagn Lab Immunol. 2003 Nov; 10(6): 979–981. The withdrawal of lamivudine in the presence of M184V quickly makes wild type virus reappear, from which we can deduct the cost in fitness for HIV in maintaining 3TC or FTC in the regimen. Incidentally, this mutation increases susceptibility to AZT, which may be another option.
Dear Dr Alexandre Carvalho,
Valid point. M184V also increases susceptibility to Tenofovir. Some of my colleagues therefore prefer to keep lamivudine and Tenofovir despite partial resistance and add 2 new susceptible drugs
regards
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