Page 106 - HIV/AIDS Guidelines

This strategy should be avoided in patients with documented NRTI resistance unless there are other fully
active drugs in the regimen.

Because enfuvirtide (T-20) requires twice-daily injections, causes injection-site reactions, and is more
expensive than other available ARV agents, patients who are virologically suppressed on T-20-containing
regimens may wish to substitute T-20 with an active oral agent. Because the majority of patients on T-20
have highly drug-resistant virus, substitution must be with another fully active agent. Data from one
randomized trial and one observational study suggest that RAL can safely substitute for T-20 in patients not
previously treated with INSTI. 12-13 Although this strategy generally maintains virologic suppression and is
well tolerated, clinicians should be aware that any drug substitution may introduce unanticipated adverse
effects or drug-drug interactions. 14

Other newer agents that might be considered as substitutes for T-20 are etravirine (ETR) or MVC. Use of
ETR in this setting would optimally be considered only when viral susceptibility to ETR can be assured from
resistance testing performed prior to virologic suppression and after carefully assessing for possible
deleterious drug-drug interactions (e.g., ETR cannot be administered with several PIs [see Table 16b]). In the
ETR early access program, switching from T-20 to ETR showed promise in maintaining viral suppression at
15
24 weeks, but only 37 subjects were included in this report. MVC is only active in those with documented
R5-only virus, a determination that cannot routinely be made in those with undetectable HIV RNA on a
stable regimen. Although there is a commercially available proviral DNA assay to assess viral tropism in
virologically suppressed patients, there are no clinical data on whether results of this test predict the
successful use of MVC as a substitute for another active drug.
Reducing the number of active drugs in a regimen. This approach to treatment simplification involves
switching a patient from a suppressive regimen to fewer active drugs. In early studies, this approach was
associated with a higher risk of treatment failure than continuation of standard treatment with two NRTIs
16
plus a PI. More recently, studies have evaluated the use of an RTV-boosted PI as monotherapy after
virologic suppression with a two-NRTI + boosted-PI regimen. 17-18 The major motivations for this approach
are a reduction in NRTI-related toxicity and lower cost. In a randomized clinical trial, low-level viremia
18
was more common in those on maintenance LPV/r alone than on a three-drug combination regimen. Viral
suppression was achieved by resuming the NRTIs. Studies of DRV/r monotherapy, both as once- or twice-
daily dosing, have reported mixed results. 19-20 In aggregate, boosted-PI monotherapy as initial or as
21
simplification treatment has been somewhat less effective in achieving complete virologic suppression and
avoiding resistance. Therefore, this strategy cannot be recommended outside of a clinical trial.
Monitoring After Treatment Simplification

Patients should be evaluated 2–6 weeks after treatment simplification to assess tolerance and to undergo
laboratory monitoring, including HIV RNA, CD4 cell count, and markers of renal and liver function.
Assessment of fasting cholesterol subsets and triglycerides should be performed within 3 months after the
change in therapy. In the absence of any specific complaints, laboratory abnormalities, or viral rebound at
that visit, patients may resume regularly scheduled clinical and laboratory monitoring.

References

1. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication
compliance. Clin Ther. 2001;23(8):1296-1310.

2. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and
efavirenz for HIV. N Engl J Med. 2006;354(3):251-260.

3. Molina JM, Podsadecki TJ, Johnson MA, et al. A lopinavir/ritonavir-based once-daily regimen results in better
compliance and is non-inferior to a twice-daily regimen through 96 weeks. AIDS Res Hum Retroviruses.

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-13

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