To the Editor: Persistent low-level viremia is a precursor to the development of resistant mutations leading to overt treatment failure.Hence, the most updated US Department of Health and Human Services (DHHS) guidelines recommend that the goal of human immunodeficiency virus (HIV) treatment is to suppress HIV-RNA levels maximally and prevent further selection of resistance mutations, if possible. Trials of newer antiretroviral (ARV) agents have shown that it is possible to achieve plasma HIV-1 RNA levels below 50 copies/mL even in highly treatment-experienced patients. Darunavir (DRV) is an example of a newer ARV agent belonging to the class of protease inhibitors (PIs) with potent antiviral effect on wild type and resistant HIV virus. We hypothesize that patients with a low-level viremia while treated with ritonavir-boosted PI (PI/r), in the absence of genotypic mutations, will be able to achieve complete viral suppression with DRV/r. Patients were selected if they had been on a stable PI/r-containing regimen for at least 12 months and had >95% adherence by self-report and physician evaluation. Low viremia was defined as having HIV-RNA level >50 but <2000 copies/mL on 2 consecutive occasions within last 3 months before enrollment and no evidence of DRV genotypic mutations. DRV/r was added in place of PI/r without changing other agents. A total of 14 patients met these selection criteria. The median age was 55 years (range: 38-62) with 93% being male (n 1⁄4 13). The PI/r consisted of lopinavir/r in 6 patients, fosamprenavir/r in 4, atazanavir/r in 2, and lopinavir/saquinavir/r in 2. Ten patients were also receiving tenofovir and emtricitabine and 4 abacavir (ABC) and lamivudine (3TC). Genotypic testing in all patients did not disclose any resistant conferring mutation to DRV or other PIs. The median baseline CD4 count and HIV-RNA levels were, respectively, 345 cells/mm (7-586) and 774 copies/mL (2.9 log10; 139-1450). At week 12, the median CD4 count was increased by þ42 cells/mm and 93% of patients were <400 copies/mL (n 1⁄4 13). At week 24, the median CD4 count was 412 cells/ mm (þ69 from baseline; 29-837) with 100% of patients <400 copies/mL and 93% of patients <50 copies/mL (n 1⁄4 13; <50-250). Total cholesterol and triglycerides were 162 mg/dL (119-218) and 200 mg/dL (79-416) at baseline; 155 mg/dL (101268) and 120 mg/dL (72-280), respectively, at week 24. All patients tolerated DRV/r well and there were no grade 2 adverse events. Previous studies have shown the impact of mutational patterns in the presence of low-level viral replication. One such retrospective study was the continuous treatment with Trizivir (the fixed-dosed combination of ABC, 3TC, and zidovudine) in the presence of viral replication, which resulted in a stepwise accumulation of resistance mutations. Lafeuillade et al performed 2 genotypic tests on 22 HIVpositive patients while they were receiving a stable regimen of ARV drugs and maintaining viral loads between 50 and 1000 copies/mL.Almost 70% of the patients developed new mutations over a median of 28 months. In another retrospective analysis, the EuroSIDA cohort focused on 110 patients with HIV-RNA >400 copies/mL who continued on failing regimens for a median of 6 months. Overall, 77% of patients acquired 1 or more mutations over the study period. Although our study does not address the etiology of low-level viremia, it demonstrates that intensification with a potent agent is able to reduce detectable viremia, in all but one, indicating that this approach could be a viable option.

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