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Best regimen to determine resistance for phen/genotype testing.
Mar 15, 2001

Dear Doctor:

I have been HIV+ since 1986 and been on almost every drug available. I was diagnosed with PCP in 1993 and 1994 and was diagnosed with MAC shortly before starting Crixivan in 1995. At its lowest, my T-Cell count was 8. I had to stop Crixivan due to toxicity, but did achieve an undetectable VL even though I was taking Crixivan with previous antivirals. After Crixivan, I started on Nelfinavir and achieved an undetectable VL but a return to low level VL (less than 30,000) after several months. Part of this regimen included Preveon which caused mild kidney damage. I then started a ritonavir/saquinavir, sustiva, abacavir, 3TC, D4T salvage regimen which achieved an undetectable viral load for over 18 months. This regimen caused severe acid reflux and elevated blood pressure. In June, 2000, I had to stop medicines due to acute kidney failure caused by blood pressure reducing medicine. I have tried to restart my old regimen twice, once in August and again in January, but had to stop both times after a month due to gastrointestinal problems. The gastrointestinal problems are particularly worrisome due to potential for dehydration and further kidney damage.

I have been off meds except for prophylaxis since early February. My doctor and I are looking at what regimen to try next and I need your help. I was hoping I could try a regimen that doesnt include every drug known to man. My doctor wants to do phenotype and genotype resistance testing and wants me to try a bogus regimen of nelfinavir, azt and 3tc or d4t and 3tc. Or, he has suggested my old regimen minus 3tc or d4t. After a month, he would do the resistance testing and make decisions from there.

In 1997, I had a genotype with mutations at HIV gene pol amino acid #41, #67, #70, #135, #184, #210, #215 and #219.

What do you think? Any suggestions on what regimen to try in order to maximize the use of genotype and phenotype testing? Any feedback would be greatly appreciated. Your site has been a godsend over the years.

Thanks!

Response from Dr. Holodniy

The strategy proposed by your doctor has been used by many physicians to elicit resistant virus to come out after an interruption in HIV meds. The resistance test from 97 is helpful in that you have high level resistance to AZT, 3TC and abacavir. Those mutations also suggest that d4T resistance would be present (by virtue of the AZT or thymidine associated mutations). From the old test, there is no evidence of PI or NNRTI (sustiva or nevirapine) resistance. You have been exposed to 4 different PIs and one NNRTI, and we don't know the current status of their resistance, if any. TWo strategies are possible here. Restart ritonavir + either indinavir or saquinavir and sustiva and genotype in 1 month to determine the optimal approach. Or start fresh with Kaletra (lopinavir + ritonavir), ddI EC, and expanded access tenofovir. The likelihood of cross resistance with this regimen would be low.MH



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