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.

To the Editor: Tolerability and potential for long-term treatment adherence are critical components of a successful human immunodeficiency virus (HIV) treatment regimen. Approval of newer classes of antiretroviral (ARV) medications allows new options for HIVinfected patients. Enfuvirtide (ENF) is a potent ARV medication dosed subcutaneously twice daily in treatment-experienced HIV-infected patients. In clinical trials, nearly all ENF-treated patients (97.6%) had at least 1 injection-site reaction. A total of 11 patients (3.3%) in the ENF group and 3 patients in the control group who switched to ENF (2.6%) discontinued treatment with ENF owing to injection-site reactions. Other difficulties reported were dislike of self-injection and storage of needles and injection paraphernalia. Raltegravir (RAL) is the first in a new class of integrase inhibitors that was approved by the US Food and Drug Administration (FDA) for use in treatment-experienced adult patients who have evidence of viral replication and HIV strains resistant to multiple ARV drugs. It has demonstrated potent efficacy through 48 weeks in 2 controlled studies that were conducted in clinically advanced, 3-class ARV medication, treatment-experienced adults. We conducted a study to access the virologic and quality of life effects of changing ENF to RAL in HIV-infected patients with an undetectable viral load, defined as HIV-RNA levels <50 copies/mL. This was a multicenter, open label, historical controlled study, which included patients from 6 AIDS Healthcare Foundation’s Clinics in California. Patients who were 18 years or older, who were receiving a stable ARV regimen containing ENF for >6 months, with HIV-RNA levels <50 copies/mL and no previous use of RAL or elvitegravir were asked to participate. Patients who were willing had their ARV medication changed from ENF to RAL with no other ARV medication change. Human immunodeficiency virus-1 RNA measurements and CD4 counts were performed at baseline, week 12, and week 24. A quality of life questionnaire was administered at week 12. A total of 25 patients met our inclusion criteria (24 men and 1 woman). The mean age was 49 years (range 33-64). The baseline CD4 count was 332 cells/mm (range 155-538). In all, 60% (15) of patients completed the quality of life questionnaire whose results are summarized in Table 1. All the patients (22/22) who were followed at 6 months maintained an HIV-RNA level <48 copies/ mL and an average CD4 count of 370 cells/mm (range 211-700). In all, 2 patients were lost to follow up and 1 died from head trauma. Few prior studies have shown the virologic effect of switching ENF to RAL in virologically suppressed patients. One study showed all 35 patients having maintained undetectable viral loads for several months. In another report, 18 participants on ENF for a median of 21 months discontinued this agent in favor of RAL and all maintained virologic suppression for more than 12 weeks. A larger study showed that 94% of 52 patients were able to maintain viral suppression at 12 weeks and their CD4 counts increased by an average of þ32 cells/mm In summary, our findings show that a switch from ENF to RAL in virologically suppressed patients who are highly treatment-experienced maintain both virologic and immunologic efficacy up to 24 weeks.

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