Genotypic resistance in HIV-1-infected patients with persistently detectable low-level viremia while receiving highly active antiretroviral therapy

Background. Technical limitations in the sensitivity of commercial genotyping methods may prevent clinicians from determining whether drug-resistant human immunodeficiency virus type 1 (HIV-1) is present in patients with low-level viremia. We performed ultrasensitive HIV-1 genotyping for patients with persistent plasma virus loads of 50-400 copies/mL to better define the prevalence of drug resistance and the most common resistance mutations during persistently detectable low-level viremia. Methods. Genotyping of HIV-1 was performed with an ultrasensitive clonal genotyping method. Results. We studied 21 patients who had persistent, detectable, low-level viremia for a median of 11 months. Nine (43%) of 21 patients had HIV-1 isolates with significant resistance mutations. The most common mutations were M184V, K65R, and M41L/T215Y. Conclusions. The finding that clinically significant resistance mutations were present in some but not all patients with persistent viremia (range, 50-400 copies/mL) highlights the need to improve the sensitivity of current clinical assays for detection of drug resistance.