Treatment interruptions of three months or under do not appear to either
improve or worsen the risk of disease progression in people with HIV, particularly those
with a high CD4 count and low viral load, according to a major Swiss cohort
study.
However, the study authors are urging caution and point out that
people with a low CD4 count and high viral load are at greater risk of death
or disease progression after initiating a treatment break. This is because CD4 cell counts tend to return towards the pre-treatment low after treatment interruptions, and people with low CD4 cell counts at the time of treatment interruption tend to be those individuals who had very advanced HIV disease at the time they began Highly Active Antiretroviral Therapy (HAART).
The study reinforces the message of a number of other analyses carried out in the past two years, all of which have reached similar conclusions.
Between January 1996 and October 2000 the effect of treatment interruptions
of between one and three months in 1299 people taking a combination of at
least two nucleoside analogues (NRTIs) plus a protease inhibitor or the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine or
efavirenz were monitored. These were compared to the 3421 Swiss people on
HAART who did not take a break in their treatment.
Data were collected on the CD4 counts, viral load, treatment history, stage
of HIV disease, age, intravenous drug use and mode of HIV transmission of
people taking one or more treatment breaks and their clinical progression
was compared to people within the Swiss cohort who remained on uninterrupted
therapy.
In particular the Swiss researchers looked at rates of death, the
occurrence of CDC stage B or C (symptomatic HIV or AIDS defining illnesses),
and increases in CD4 cell count of 5O cells/mm3 or more in people whose baseline count was
below 500 cells/mm3.
Treatment interruptions were overwhelmingly
initiated for social reasons (63 per cent) or intolerance (30 per cent),
with only seven per cent of cases attributable to treatment failure.
CD4 count was comparable at baseline in both groups, however, people taking
interruptions were more likely to have a higher baseline viral load. In
addition those initiating a treatment interruption had been infected with
HIV for an average of a little over three years (compared to two years for
the non-interruption group), were more extensively pretreated, had fewer
educational qualifications, and had experienced more disease progression.
The Swiss researchers found a
slightly higher risk of death amongst people taking a treatment break,
particularly those with a CD4 count below 200 cells/mm3 and a previous
symptomatic HIV or AIDS defining illness. Other factors associated with an
increased risk of death were age, intravenous drug use and higher viral
load.
Overall the risk of developing symptomatic HIV-related illness was not
significantly affected by interruptions, but was greater for patients with
high viral loads and lower CD4 counts. As regards AIDS defining illness, a
treatment interruption led to a slightly increased risk, as did age and
pretreatment.
People taking treatment breaks were less likely to see an increase in their
CD4 count, but this did not appear to worsen in those taking multiple
breaks. However, people with little or no HIV disease progression and a high
viral load did experience an increase in baseline CD4 count.
On the basis of this data, the Swiss researchers concluded "that
interruptions of HAART did not significantly increase the risk of
HIV-associated morbidity and mortality, except for a statistically marginal
increased risk for a CDC stage C event after the first interruption...from a
clinical point of view, short interruptions do not bear a high risk of
clinical progression, neither do they improve the later clinical course."
However, the authors point out: "the higher the viremia, the lower the CD4
count, the older the patient, and the longer the duration of HIV, the worse
the prognosis." They also point out the potential for biases in
observational studies, and call for further research to confirm their
finding, recommending "extreme caution" when deciding to interrupt HAART.
Taffe P et al. Impact of occasional short interruptions of HAART on the
progression of HIV infection: results from a cohort study AIDS 16:747-755, 2002.