In an effort to reduce the side effects, long-term
toxicities, inconvenience, and cost of antiretroviral therapy, researchers have
explored structure treatment interruption (STI), in
which patients stop therapy periodically either according to a fixed schedule
or based on changing CD4 cell counts. But results to date indicate that treatment
interruption is a risky strategy that does not deliver the anticipated benefits.
The
SMART study
was one of the largest-ever CD4 cell-guided STI trials. SMART included 5472 mostly
treatment-experienced participants who enrolled with a CD4 cell count above 350
cells/mm3 and were randomly assigned to 2 treatment strategy arms. Patients in
the "drug conservation" (treatment interruption) arm stopped antiretroviral
therapy when their CD4 cell count reached 350 cells/mm3 and resumed treatment
when it fell back down to 250 cells/mm3. Those in the "viral suppression"
(continuous therapy) arm remained on antiretroviral therapy throughout the study.
SMART was cancelled ahead of schedule in January 2006 after it became
apparent that participants in the treatment interruption arm had higher rates
of morbidity and mortality compared with those receiving continuous therapy. As
previously reported patients in the treatment interruption arm were 2.6 times
more likely to experience opportunistic illnesses or death; unexpectedly, they
also had a higher rate of non-opportunistic conditions such as heart, liver, and
kidney disease.
Now, in the February 1, 2008 Journal of Acquired Immune
Deficiency Syndromes, SMART researchers report that treatment interruption
was not associated with any improvement in quality of life (QOL), which was one
of the primary rationales for this strategy; these data were previously reported
at the XVI International AIDS Conference in Toronto in August 2006.
In
the present analysis, QOL was assessed using an analog scale for current health
and the Short-Form 12-Item Survey, a standard abbreviated QOL instrument. A total
of 1225 SMART participants received QOL assessments over a mean follow-up period
of 2.4 years, at first every 4 months and later annually.
Three-quarters
of the participants were men. Most (76%) were on antiretroviral therapy at the
time of study enrollment. The median CD4 count was 575 cells/mm3 (interquartile
range 455 to 784). The average current health rating was 75 on a scale of 0 to
100, and 50% reported very good or excellent general health.
Results
•
Throughout the follow-up period, whenever QOL outcomes
differed, the results were inferior among patients in the treatment interruption
arm compared with the continuous therapy group.
•
Current health, Physical Health Component Score (both
P = 0.05), general health perceptions, physical functioning, and energy
(all P = 0.03) were all higher in the continuous therapy group.
•
HIV disease progression (opportunistic disease or death)
was more common in the treatment interruption arm, and was preceded by marked
declines in QOL.
•
However, excluding participants who experienced disease
progression had a minimal effect on QOL comparisons.
Conclusion
In
conclusion, the study authors wrote, "CD4 count-guided episodic use of antiretroviral
therapy resulted in inferior QOL compared with continuous therapy." These
findings add to the growing body of data showing that periodic CD4 cell-guided
treatment interruption is an inferior strategy that can be hazardous to patients,
with little -- if any -- benefit.
At the 48th Conference on Retroviruses
and Opportunistic Infections (CROI) next week (Monday, February 4, 2008), SMART
researchers will present new data on the outcomes of re-introducing antiretroviral
therapy after treatment interruption.
1/29/08
Reference WJ
Burman, B Grund, M Roediger, and others (SMART Study Group). The Impact of Episodic
CD4 Cell Count-Guided Antiretroviral Therapy on Quality of Life. JAIDS
47(2): 185-193. February 1, 2008.
