Page 113 - HIV/AIDS Guidelines

Planned Long-Term Therapy Interruptions

Planned therapy interruptions have been contemplated in various scenarios, listed below. Research is
ongoing in several of the scenarios. Therapy interruptions cannot be recommended at this time outside of
controlled clinical trials (AI).

• In patients who initiated therapy during acute HIV infection and achieved virologic suppression—
the optimal duration of treatment and the consequences of treatment interruption are not known at this
time. (See Acute HIV Infection.)
• In patients who have had exposure to multiple ARV agents, have experienced ARV treatment
failure, and have few treatment options available because of extensive resistance mutations—
interruption is not recommended unless done in a clinical trial setting (AI). Several clinical trials,
largely yielding negative results, but some with conflicting results, have been conducted to better
understand the role of treatment interruption in these patients. 1-4 The largest of these studies showed
1
negative clinical impact of treatment interruption in these patients. The Panel notes that partial virologic
5
suppression from combination therapy has been associated with clinical benefit; therefore, interruption
of therapy is not recommended.
• In patients on ART who have maintained a CD4 count above the level currently recommended for
treatment initiation and irrespective of whether their baseline CD4 counts were either above or
below that recommended threshold—interruption is also not recommended unless done in a clinical
trial setting (BI). (See discussion below highlighting potential adverse outcomes seen in some treatment
interruption trials.)
Temporary treatment interruption to reduce inconvenience, potential long-term toxicity, and/or overall
treatment cost has been considered as a strategy for patients on ART who have maintained CD4 counts above
those currently recommended for initiating therapy. Several clinical trials have been designed to determine
the safety of such interruptions, in which reinitiation is triggered by predetermined CD4 count thresholds. In
these trials, various CD4 count levels have been set to guide both treatment interruption and reinitiation. In
the SMART study, the largest of such trials with more than 5,000 subjects, interrupting treatment with CD4
3
counts >350 cells/mm and reinitiating when <250 cells/mm was associated with an increased risk of
3
disease progression and all cause mortality compared with the trial arm of continuous ART. In the
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TRIVACAN study, the same CD4 count thresholds were used for stopping and restarting treatment. This
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study also showed that interruption was an inferior strategy; the interventions in both trials were stopped
early because of these findings. Data from the DART trial reported a twofold increase in rates of World
Health Organization (WHO) Stage 4 events/deaths in the 12-week ART cycling group among African
patients achieving a CD4 count >300/mm compared with the continuous ART group. Observational data
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3
from the EuroSIDA cohort noted a twofold increase in risk of death after a treatment interruption of >3
months. Factors linked to increased risk of death or progression included lower CD4 counts, higher viral
loads, and a prior history of AIDS. Other studies have reported no major safety concerns, 10-12 but these
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studies had smaller sample sizes. Results have been reported from several small observational studies
evaluating treatment interruption in patients doing well with nadir CD4 counts >350/mm , but further studies
3
are needed to determine the safety of treatment interruption in this population. 13-14 There is concern that CD4
counts <500 cells/mm are associated with a range of non-AIDS clinical events (e.g., cancer and heart, liver,
3
and kidney disease). 6, 15-16

Planned long-term therapy interruption strategies cannot be recommended at this time outside of controlled
clinical trials (BI) based on available data and a range of ongoing concerns.
If therapy has to be discontinued, patients should be counseled about the need for close clinical and
laboratory monitoring. They should also be aware of the risks of viral rebound, acute retroviral syndrome,

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-20

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