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Case 1: Indications for Resistance Testing

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D A 35-year-old woman who previously had an HIV RNA level of 16,700 copies/ml while taking the regimen of stavudine (Zerit) plus lamivudine (Epivir) plus efavirenz (Sustiva). She admits to spotty adherence while taking that regimen and she discontinued all of her antiretroviral medications 24 weeks ago. She now wants to restart antiretroviral therapy and states she is highly motivated to have excellent adherence.

This answer is correct. Although this patient likely developed resistance while intermittently taking stavudine plus lamivudine and efavirenz, she has not been taking these medications for 24 weeks. It is likely that without the selective pressure of the medications, wild type virus would have overgrown most of the resistant virus. Hence any resistant strains that developed while she was taking the medications would likely become a minor species and thus less likely to be detected by the resistance assay. For this reason, the DHHS antiretroviral guidelines recommend that resistance testing is usually not recommend in the setting when patients have been off medications for longer than 4 weeks. It should be noted, however, that recent data have suggested that some mutations that confer high level resistance to the NNRTI class of drugs, such as the K103N mutation, may persist for many months in some patients, even in the absence drug pressure, presumably because these mutations do not significantly impair the replicative capacity of HIV. It is important for clinicians to understand that if they perform a resistance assay in this setting, the absence of detectable resistance does not rule out the presence of minor drug-resistant species.

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