HIV-positive patients who take breaks from their
antiretroviral therapy have poorer increases in their CD4 cell count, are more
likely to develop HIV-related illness, and have a higher risk of death than
individuals who take continuous treatment, and these risks persist for at least eight years after the treatment break, Swiss investigators report in the
online edition of AIDS.
The research also showed that longer breaks from treatment
were associated with especially poor outcomes.
“The results strongly support the concept that patients
should be discouraged to discontinue antiretroviral therapy,” comment the
There have been significant improvements in HIV therapy in
recent years, and the prognosis for many patients is now considered normal.
However, large numbers of patients taking antiretroviral
drugs interrupt their treatment. The SMART
study showed that treatment interruptions were associated with an increased
risk of illness and death from both HIV-related and non-HIV-related illnesses.
But follow-up in the SMART study was relatively short
(median 22 months). Because HIV treatment is life-long, Swiss investigators
wished to see the implications of treatment interruptions in patients taking
long-term antiretroviral therapy.
Their study population comprised 2491 individuals who
started HIV treatment between 1996 and 2008.
They were divided into three groups according to their use
of treatment and outcomes.
The first group (51%) comprised patients who interrupted
their treatment at least once. The second (19%) included those who took
continuous therapy but who sometimes had a viral load above 1000 copies/ml. The
final group of patients were those who took uninterrupted therapy and
maintained a viral load below 1000 copies/ml.
Over a median of seven years of follow-up, changes
in CD4 cell count, rates of HIV-related illness and mortality rates were
compared between the three groups.
Average CD4 cell count increased from 210 cells/mm3
at baseline to 491 cells/mm3 after eight years. However, CD4 cell
gains differed significantly between the three groups of patients.
Only 63% of patients who took a treatment break had an
increase in their CD4 cell count to above 350 cells/mm3. This
compared to 73% of those who took continuous therapy and occasionally had a
viral load above 1000 copies/ml and 87% of individuals who took continuous
therapy with good viral suppression (p < 0.001 for both comparisons).
Patients who interrupted their therapy were also
significantly less likely to have an increase in their CD4 cell count above 500
cells/mm3 (37% vs. 56% vs. 68%, p < 0.001).
Individuals who took the longest treatment breaks had the
poorest increases in their CD4 cell counts (p < 0.001). Indeed, individuals
whose interruption lasted 31 months or more had a slight fall in their CD4 cell
count from baseline.
Statistical analysis showed that patients who interrupted
therapy were significantly less likely to achieve either a CD4 cell count above
350 cells/mm3 (p = 0.001) or above 500 cells/mm3.
Other factors associated with CD4 cell count increases to
below these levels included older age (p= 0.001 and p < 0.001
respectively), co-infection with
hepatitis C virus (p < 0.001 and p < 0.003) and starting HIV treatment at
a lower CD4 cell count (p < 0.001 for outcomes).
Taking treatment breaks also had clinical significance.
HIV-related illnesses such as oral hairy leukoplakia, oral thrush, and herpes
were more common in those who interrupted therapy and the other two groups of
patients (p = 0.013 and p = 0.034 respectively).
Similarly, individuals who stopped treatment were more
likely to develop an AIDS-defining illness than those who took continuous
treatment and had occasional viral load above 1000 copies/ml (p = 0.001) and
individuals taking therapy all the time with viral suppression (p < 0.001).
Longer duration of treatment interruption was also
associated with poorer outcomes. A total of 6% of patients who took a treatment
break lasting under a month developed an AIDS-defining illness, and this
increased to 11% for those taking breaks lasting over six months and 14% among
those whose interruption lasted 31 months or more.
“If any interruption is required, it should be as short as
possible to avoid poor clinical outcomes,” comment the investigators.
Mortality rates were highest among patients who interrupted
therapy (20 per 1000 person years) and lowest for those whose treatment was
continuous and suppressed viral load to below 1000 copies/ml (8 per 1000 person
years). In addition, HIV-related mortality was 4 per 1000 person years for
those interrupting therapy, but just 2 per 1000 person years when therapy was
taken without interruption and was virologically suppressive.
Unlike the SMART study, the investigators found no evidence
that treatment interruptions increased the risk of death from cardiovascular
disease, rates of which were similarly low in all three groups of patients.
“The absolute risk of cardiovascular events remained low,”
the researchers note.
The investigators believe their study “adds important new
information on the long-term clinical consequences of treatment interruptions
and the effect of duration of treatment interruptions.” They write that their
findings show “an interruption of ART for 6 months or more resulted in
sub-optimal recovery of CD4 T lymphocytes and increased risk of opportunistic
complications or death.”
To achieve the best outcomes in patients the authors suggest
“it appears to be essential to initiate ART early, avoid treatment
interruptions and suppress plasma HIV-1 RNA to values as low as possible."