Treatment Interruption as a Viable Option in Patients with Lowest
CD4 Cell Count >250 Cells
HAART
has contributed significantly to improved quality of life and has increased survival
in individuals living with HIV infection. However, the effectiveness
and desirability of HAART has its limitations as evidenced by
frustration over large pill count, toxicities
and side effects, and drug resistance.
These
limitations have often led to poor adherence
to therapy and the loss of sustained viral suppression and clinical
decline.
A
widely employed means of possibly ameliorating these problems
is the strategy of Treatment Interruption (TI).
This strategy is most commonly used either in
a cyclic approach based on predetermined time cycles (e.g., alternating 1 week of taking with 1 week of not taking the medications) or
in a program of cessation and re-initiation based
on predetermined parameters (e.g., symptoms and thresholds for CD4 cell count and viral load).
Theoretically, TI in either format may decrease the cumulative time a patient is exposed to antiretroviral
therapy, and thereby drug toxicity is
reduced, the development of drug resistance is
slowed, and costs to patients or the health
care system are decreased.
The
role of TI within the modern HAART strategy
remains controversial.
Beginning
in 2000, researchers in British Columbia, Canada offered TI to any HIV-positive adult who was without an AIDS-defining illness and had a nadir CD4 cell
count >200 cells/mm3. Patients who agreed to interrupt HAART were offered monthly
monitoring, including measurement of CD4 cell count
and plasma viral load.
They were also encouraged to reinitiate HAART
on the basis of present guidelines-namely, the development of an AIDS-defining illness or a
CD4 cell count </= 200 cells/mm3.
The goal
of the study was to characterize outcome
and predictors of outcome of treatment interruption
(TI) in these HAART-treated patients. Collected data included duration and reason for TI, demographic
characteristics, CD4 cell count, and plasma
viral load. Results of the study, conducted by Adrienne Toulson,
MD, and colleagues at the University of British Columbia (BC), Vancouver,
BC, appear in the November 15, 2005 issue of
The Journal of infectious Diseases.
Results
- 208
of 4461 (4.7%) patients underwent TI.
- The
study group consisted of 197 (94.7%) of 208
participants for whom V3 genotyping
was successful.
- The
median CD4 cell count at time of the initiation
of TI was 620 cells/mm3. A total
of 59 (29.9%) patients reinitiated HAART after a median of 15 months.
- At
the time of the re-initiation of HAART,
the median plasma viral load was >100,000 copies/mL, and the median CD4 cell count was 260 cells/mm3.
- Among
the 197 study patients, there were 6 deaths,
none of which was attributable to the
TI.
- A total of 81% had plasma viral loads <50 copies/mL by 15 months of follow-up after re-initiation of HAART.
- In multivariate analysis, a nadir CD4 cell count </=250
cells/mm3 and the presence of the 11/25
genotype were positively and independently associated with faster time to HAART re-initiation, after
adjusting for age and plasma virus load
at the start of TI.
Our
study suggests that TI is a viable option
for HIV-positive adults with nadir CD4 cell
counts >250 cells/mm3. A nadir CD4 cell count of 200
250 cells/mm3
and the 11/25 viral genotype were found to
be associated with a faster HAART re-initiation.
Discussion
The
results of the present and other studies of a TI strategy demonstrate
that the interruption of HAART consistently leads to
a decrease in CD4 cell count and an increase in HIV viral load, often to pre-treatment levels. The authors
emphasize that because of this fact, “caution is warranted
in recommending TI to patients with low CD4
cell counts, [as it may] put them at risk for disease progression and, after the re-initiation of HAART,
their CD4 cell counts may not return to
baseline levels for several months.”
According
to the study authors, the present study shows that
a nadir CD4 cell count <250 cells/mm3 and
a high plasma viral load at the initiation
of TI suggest that there will be a faster
time to the re-initiation of HAART.
The
researchers recommend that “physicians should also take into
account CD4 cell count variability, which approaches 30%.” If a patient’s CD4 cell count was at approximately
250 cells/mm3 when starting the TI, “ this could
reflect a CD4 cell count that is as low
as 175 cells/mm3; hence, these patients are more likely to need to reinitiate HAART sooner than patients whose CD4 cell counts are >250 cells/mm3.
“In summary,” write the authors, “the results
of our study suggest that TI is a viable
option for HIV-positive adults without an
AIDS-defining illness and with nadir CD4 cell counts >250 cells/mm3. [emphasis added—Ed].
A nadir CD4 cell count of 200250 cells/mm3
and the 11/25 genotype were found to be
associated with a faster time to the re-initiation
of HAART. “This information should be valuable
when considering a TI,” note the authors, “particularly
for patients who initiated HAART during
the past several years in accordance with present
guidelines.”
BC Centre for Excellence in HIV/AIDS and Departments of
Pathology and Laboratory Medicine, Medicine, and Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
10/21/05
Reference
A R Toulson and others. Treatment Interruption of Highly Active Antiretroviral Therapy in Patients with Nadir CD4 Cell Counts >200 Cells/mm3. The Journal
of Infectious Diseases 192(10): 1787-1793. November 15,
2005.
