The current guidelines [2, 19] recommend the use of a staggered interruption strategy in patients who must interrupt an NNRTI-based regimen. The duration of the use of NRTIs after the discontinuation of the NNRTI regimen ranged from 1 to 3 weeks [2, 8, 19]. However, the optimal duration has not been determined.
In this study, the patients in the Staggered Interruption group, who continued the use of 2 NRTIs for a median of 7 days after discontinuing NVP, had virological outcomes comparable to those of the Control group (Figure 1 and Table 2). These results are in accordance with a post-study analysis of the Strategies for Management of Antiretroviral Therapy (SMART) trial by Fox et al. . Consequently, it should be appropriate to use a staggered interruption strategy if the NRTIs are to be continued for 7 days.
Among the HIV-infected patients who received an NVP-based regimen for at least 2 weeks, the duration of detectable NVP levels after discontinuation varied from 7 to 21 days [20, 21]. Thus, patients who experience acute allergic reactions to an NVP-based regimen may acquire NNRTI-resistant mutations if they simultaneously stop all the drugs in the NVP-based regimen. A simultaneous interruption strategy for discontinuing NNRTI-based regimens is not recommended in the current DHHS guidelines . In this study, there was a higher incidence of virological failure and genotypic resistance mutations to NNRTI in the Simultaneous Interruption group than in the other groups. Thus, a simultaneous interruption strategy is not advisable.
The median follow-up time duration of the Simultaneous Interruption group was significantly longer than those of the other groups (p<0.001) (Table 1). This result may have been influenced by a general recommendation in the DHHS guidelines (the November 3, 2008 version)  that a staggered interruption strategy should be employed to prevent NNRTI resistance after discontinuing NNRTI-based regimens. In this study, there were 141 (88%) patients in the Simultaneous Interruption group who began an EFV-based regimen prior to November 3, 2008.
The current guidelines recommend that patient plasma HIV-1 RNA levels and CD4 cell counts be monitored regularly, at least twice per year [1, 2, 22]. Nevertheless, the plasma HIV-1 RNA levels of 21% of the cohort were assayed less than once per year. Thus, the final evaluation was designed to assess the laboratory data of the patients who remained in the cohort through the end of study. The evaluation may have produced a more accurate diagnosis of laboratory-related events and data, such as virological outcomes and laboratory adverse events.
In the beginning of the study, d4T/3TC was commonly administered to our patients (Figure 1) because TDF was not available in our hospital until January 2007.
The low incidence of virological failure may have resulted from the removal from the cohort of patients who were lost to follow-up (e.g., either a documented discontinuation of an EFV-based regimen for more than 3 months or a failure to attend a follow-up examination at the hospital for longer than 3 months after the original appointment date). These patients generally exhibited low compliance with ARV therapy, which is associated with virological failure [23, 24].
This study had the following limitations: (a) a retrospective design; (b) a non-randomized design; (c) some incomplete data (including CD4 cell counts, plasma HIV-1 RNA levels, and the results of genotypic resistance assays); (d) a follow-up loss of 9.5%; and (e) the frequent use, in the beginning of the study, of NRTI drugs such as d4T/3TC that are not preferred NRTIs under the current guidelines (1, 2, 22). These limitations should be carefully considered when interpreting the data from this study.