Likelihood of Resistance in Treatment-Experienced Patient?
Likelihood of Resistance in Treatment-Experienced Patient?
I have recently taken over the care of a patient diagnosed with HIV in 1993, who has been off and on several antiretroviral regimens and has achieved successful viral suppression at times (although I do not have accurate records). However, he had problems tolerating a number of antiretrovirals, including peripheral neuropathy with stavudine and didanosine, CNS effects with efavirenz, and gastrointestinal intolerance with ritonavir, saquinavir, and nelfinavir.
His most recent regimen was ritonavir/amprenavir/zidovudine/lamivudine for about 1 year, with a CD4+ cell count of 787 cells/mm and viral load < 400 copies/mL. Unfortunately he felt vaguely "ill" all the time and requested treatment interruption for 3 months. He felt much better overall off medications, but his CD4+ cell count dropped to 256 and viral load became detectable at 63,000.
Can I assume that he still may be drug-sensitive to previously used medications and re-try the ones he seemed to tolerate? Is he likely to be nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, having previously been exposed to efavirenz, delavirdine, and nevirapine (though I have no data on virologic responses to them) since he always gets intolerant to some part of the regimen? I will probably order a genotype assay the next time he is on a failing regimen -- but where can I learn how to interpret these tests?
Before considering the use of recycled medications he has taken before, you might try resuming the same regimen that he was using successfully before the treatment interruption. Because your patient had an undetectable virus load at the time treatment was interrupted, it is highly likely that the virus remains susceptible to the drugs used in that regimen. Most studies show that there is little or no accumulation of drug resistance mutations in virus from patients who maintain virus load < 50 copies/mL while on antiretroviral therapy.
The chances are good that the patient's virus carries one or more NNRTI resistance mutations. These mutations tend to be more stable than those associated with resistance to lamivudine or protease inhibitors, as demonstrated in an abstract by Joly and colleagues at The 1st IAS Conference on HIV Pathogenesis and Treatment in Buenos Aires, Argentina, in July 2001. The K103N mutation persisted in virus from 37% of patients and the Y181C mutation persisted in virus from 45% of patients 12 months after discontinuing NNRTI use.
There are a number of Web sites that offer guidance on interpreting resistance test results. A good place to start is the general review of drug resistance on Medscape. For interpretation of specific test results, try the Stanford HIV RT and Protease Sequence Database or the Los Alamos HIV Sequence Database Web sites.
I have recently taken over the care of a patient diagnosed with HIV in 1993, who has been off and on several antiretroviral regimens and has achieved successful viral suppression at times (although I do not have accurate records). However, he had problems tolerating a number of antiretrovirals, including peripheral neuropathy with stavudine and didanosine, CNS effects with efavirenz, and gastrointestinal intolerance with ritonavir, saquinavir, and nelfinavir.
His most recent regimen was ritonavir/amprenavir/zidovudine/lamivudine for about 1 year, with a CD4+ cell count of 787 cells/mm and viral load < 400 copies/mL. Unfortunately he felt vaguely "ill" all the time and requested treatment interruption for 3 months. He felt much better overall off medications, but his CD4+ cell count dropped to 256 and viral load became detectable at 63,000.
Can I assume that he still may be drug-sensitive to previously used medications and re-try the ones he seemed to tolerate? Is he likely to be nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, having previously been exposed to efavirenz, delavirdine, and nevirapine (though I have no data on virologic responses to them) since he always gets intolerant to some part of the regimen? I will probably order a genotype assay the next time he is on a failing regimen -- but where can I learn how to interpret these tests?
Before considering the use of recycled medications he has taken before, you might try resuming the same regimen that he was using successfully before the treatment interruption. Because your patient had an undetectable virus load at the time treatment was interrupted, it is highly likely that the virus remains susceptible to the drugs used in that regimen. Most studies show that there is little or no accumulation of drug resistance mutations in virus from patients who maintain virus load < 50 copies/mL while on antiretroviral therapy.
The chances are good that the patient's virus carries one or more NNRTI resistance mutations. These mutations tend to be more stable than those associated with resistance to lamivudine or protease inhibitors, as demonstrated in an abstract by Joly and colleagues at The 1st IAS Conference on HIV Pathogenesis and Treatment in Buenos Aires, Argentina, in July 2001. The K103N mutation persisted in virus from 37% of patients and the Y181C mutation persisted in virus from 45% of patients 12 months after discontinuing NNRTI use.
There are a number of Web sites that offer guidance on interpreting resistance test results. A good place to start is the general review of drug resistance on Medscape. For interpretation of specific test results, try the Stanford HIV RT and Protease Sequence Database or the Los Alamos HIV Sequence Database Web sites.
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