HIV Drug-Resistance Mutations Emerge in Patients with Low-Level Viremia
Adherence counseling or regimen changes may be warranted for patients on ART whose viral loads are repeatedly >200 copies/mL.
Patients who develop low-level viremia (LLV) while receiving antiretroviral therapy (ART) may be at increased risk for viral rebound, but we do not yet know what to do for such patients (JW AIDS Clin Care Aug 20 2012). In the present study, researchers evaluated whether new drug-resistance mutations develop during LLV, a factor that could influence clinical management.
Drawing from a large, prospective study of HIV-infected patients in California, the investigators identified 47 patients who experienced LLV (defined as a viral load <1000 copies/mL) while receiving ART; 89% were treatment experienced at study entry. Drug-resistance genotyping was performed on 82 samples obtained during periods of LLV between 2001 and 2010. The median viral load in these samples was 267 copies/mL (range, 174–414 copies/mL).
Nearly half of the samples (46%) were found to have new HIV drug-resistance mutations when compared with prior genotypes. Of the 18 patients who had more than one episode of LLV, 8 (44%) accumulated new drug-resistance mutations over a median of 11 months. (Several of these patients were receiving drug combinations that are less potent than current regimens.) Risk factors for the accumulation of resistance included receipt of fewer active drugs and longer time since an episode of LLV. Most LLV episodes (76%) were followed by virologic suppression.
Comment: This small but important study suggests that patients on ART with persistent LLV (viral loads between 200 and 1000 copies/mL) have a substantial risk for developing HIV drug-resistance mutations. Because most patients in this study were treatment experienced, some of the mutations may represent archived resistance; moreover, many of the patients who developed new mutations were on outdated regimens. Nevertheless, this study suggests that patients with persistent viral loads of approximately 200 copies/mL or greater should have intensified adherence counseling or a change in regimen. It is less clear what we should do, if anything, in patients with lower levels of detectable viremia — an issue that is coming up more frequently as the detection threshold for viral-load assays continues to go down.
Published in Journal Watch HIV/AIDS Clinical Care November 5, 2012
Li JZ et al. Prevalence and significance of HIV-1 drug resistance mutations among patients on antiretroviral therapy with detectable low-level viremia. Antimicrob Agents Chemother 2012 Nov; 56:5998.
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