Page 104 - HIV/AIDS Guidelines

Regimen Simplification (Last updated January 10, 2011; last reviewed January 10, 2011)
Regimen simplification can be defined broadly as a change in established effective therapy to reduce pill
burden and dosing frequency, to enhance tolerability, or to decrease specific food and fluid requirements.
Many patients on suppressive antiretroviral therapy (ART) may be considered candidates for regimen
simplification, especially if (1) they are receiving treatments that are no longer recommended as preferred or
alternative choices for initial therapy; (2) they were prescribed a regimen in the setting of treatment failure at
a time when there was an incomplete understanding of resistance or drug-drug interaction data; or (3) they
were prescribed a regimen prior to the availability of newer options or formulations that might be easier to
administer and/or more tolerable.

This section will review situations in which clinicians might consider simplifying treatment in a patient with
virologic suppression. Importantly, this section will not review consideration of changes in treatment for
reducing ongoing adverse effects. Regimens used in simplification strategies generally should be those that
have proven high efficacy in antiretroviral (ARV)-naive patients (see What to Start) or that would be predicted
to be highly active for a given patient based on the individual’s past treatment history and resistance profile.

Rationale
The major rationales behind regimen simplification are to improve the patient’s quality of life, maintain long-
term adherence, avoid toxicities that may develop with prolonged ARV use, and reduce the risk of virologic
failure. Systematic reviews in the non-HIV literature have shown that adherence is inversely related to the
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number of daily doses. Some prospective studies in HIV-infected individuals have shown that those on
regimens with reduced dosing frequency have higher levels of adherence. 2-3 Patient satisfaction with
regimens that contain fewer pills and reduced dosing frequency is also higher. 4

Candidates for Regimen Simplification
Unlike ARV agents developed earlier in the HIV epidemic, many ARV medications approved in recent years
have sufficiently long half-lives to allow for once-daily dosing, and most also do not have dietary
restrictions. Patients on regimens initiated earlier in the era of potent combination ART with drugs that pose a
high pill burden and/or frequent dosing requirements are often good candidates for regimen simplification.
Patients without suspected drug-resistant virus. Patients on first (or modified) treatment regimens without
a history of treatment failure are ideal candidates for regimen simplification. These patients are less likely to
harbor drug-resistant virus, especially if a pretreatment genotype did not detect drug resistance. Prospective
clinical studies have demonstrated that the likelihood of treatment failure is relatively low in patients after
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simplification and, indeed, may be lower than in patients who do not simplify treatment. However, some
patients may have unrecognized drug-resistant HIV, either acquired at the time of infection or as a
consequence of prior treatment, such as patients who were treated with presumably nonsuppressive mono- or
dual-nucleoside reverse transcriptase inhibitor (NRTI) regimens before the widespread availability of HIV
RNA monitoring and resistance testing.

Patients with documented or suspected drug resistance. Treatment simplification may also be appropriate
for selected individuals who achieve viral suppression after having had documented or suspected drug
resistance. Often, these patients are on regimens selected when management of drug resistance,
understanding of potentially adverse drug-drug interactions, and understanding of treatment options were
relatively limited. Regimen simplification may also be considered for patients on two ritonavir (RTV)-
boosted protease inhibitors (PIs). Although successful in suppressing viral replication, this treatment may
cause patients to be on regimens that are cumbersome, costly, and associated with potential long-term
adverse events. The ability to simplify regimens in this setting often reflects the availability of recently
approved agents that have activity against drug-resistant virus and are easier to take without sacrificing ARV
activity. Specific situations in which drug simplification could be considered in ART-experienced patients
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-11

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