I recently received a patient who has been on virtually all possible available drugs. His viral load was over 100,000 copies/mL and his CD4 count was 45 (10%). He has been without medications for 7 months. When he was in the hospital, a genotype was done: I have not seen the results of that test, but apparently he has multiple primary mutations associated with resistance to PIs and many NRTIs, but not to ddI or to NNRTIs. The ID MD ordered to start the patient on Kaletra only. Can you tell me why? I am going to start the patient in Kaletra/ddI/EFV and then run a genotypic test.
Is Kaletra (alone) is an option in this case? And is ordering a genotypic test before initiation of therapy (after more than 7 months with no therapy) a good idea?
Dr. Brian Conway responds: This represents a common problem in the setting of patients that have received multiple therapies (including AZT alone!!!) for many years. The genotype result should be interpreted with great caution, as it will not provide us with adequate information about the drugs hat are not part of the patient's regimen at the time of the test. This is particularly true for NNRTIs, and the absence of resistance in the test that was done may simply reflect the current absence of drug pressure. The absence of ddI resistance mutations should also be interpreted with caution, as a pattern of AZT resistance (with multiple mutations at codons 41, 70 and 215 for example) may well confer broad cross-resistance to all NRTIs.
This being said, the approach to this particular patient is to design a triple class regimen that maximizes potential efficacy. The protease inhibitor could well be Kaletra, as 6 or more mutations are required in the protease gene before decreased susceptibility is present. Although data are limited on the combination of Kaletra with delavirdine, the pharmacokinetic interactions are expected to be favorable, allowing for a lower does of Kaletra to be given (perhaps 2 capsules twice daily), and reducing the pill burden of the regimen. In fact, Kaletra/delavirdine may represent a lower pill burden than Kaletra/efavirenz (10 vs. 11). The NRTI in this regimen could be ddI, given the ease of administration of the new formulation. A genotypic resistance test should probably be done within 2-3 weeks of initiating the new regimen, to monitor the effects of this specific drug pressure on this patient's virus. This may allow for minor adjustments in the regimen to be made, if any are possible.
