The SAPIT (Starting Antiretroviral therapy at three Points In Tuberculosis therapy) trial was
designed to test three strategies for antiretroviral initiation after
starting TB treatment:
- Wait until TB
treatment is completed before starting ART (the 'deferred' arm)
- Start ART within four
weeks of completing the intensive phase of TB treatment (the 'later'
- Start ART within four
weeks of starting TB treatment (the 'early' arm).
Three years ago the
investigators of the SAPIT study reported
in the New England Journal of Medicine that starting antiretroviral treatment soon after starting TB
treatment significantly reduced the risk of death from all causes
when compared to delaying the initiation of treatment until after the
completion of TB treatment.
The SAPIT trial
continued to follow patients randomised either to start treatment
immediately or to wait until the completion of the intensive phase of
Professor Salim Abdool
Karim of the Centre for AIDS Programme Research in South Africa
(CAPRISA) presented final findings from the SAPIT study. The trial
was conducted among people with HIV infection who had been diagnosed
with smear-positive pulmonary TB in Durban, South Africa. The trial
recruited individuals with CD4 counts below 500 cells/mm3.
The trial randomised
642 patients, of whom 214 were assigned to the 'early' arm and 215 to
the 'later' arm. The remainder were assigned to the deferred group
and are not included in this analysis. 72% completed follow-up in the
early arm and 67% in the deferred arm.
The median CD4 count at
baseline was 150 cells/mm3.
All participants in the
study received a regimen of ddI, 3TC and efavirenz, designed to be
dosed once daily at the same time as directly observed short-course
TB treatment. Participants also received cotrimoxazole prophylaxis.
The primary endpoint of
the study was the measurement of changes in all-cause mortality and
new AIDS-defining illnesses.
The trial, showed that
after two years of follow-up, there was no significant difference in
the risk of AIDS or death between the early and later treatment
groups, with an event rate of 6.9 and 7.8 per 100 person years of
follow-up respectively in the two arms (p = 0.73).
Early treatment was
associated with a 68% reduction in the risk of death or AIDS when
compared to later treatment among those with CD4 counts below 50, and
the incidence rate ratio was 0,32 (p = 0.06). The rate of IRIS was
almost five times as high in the early treatment group (odds ratio
4.7, p = 0.01).
In patients with
baseline CD4 counts above 50 cells/mm3 there was no significant
benefit to early treatment, but a 2.2-fold higher risk of developing
IRIS and a 6.8-fold higher risk of switching at least one drug in the
antiretroviral regimen as a result of drug toxicity.
There was no
significant difference between the two arms in rates of TB treatment
completion or viral suppression.
Professor Karim said
that the findings support further efforts to integrate HIV care into
TB services in order to ensure rapid initiation of treatment for
those with very low CD4 counts, but for those with higher CD4 counts,
Professor Karim said the decision would remain a case-by-case
judgment for the physician.
“It really depends on
clinical judgment and the capability of the facilities to manage
cases of IRIS, and the availability of second-line drugs for
switching cases of toxicity,” said Professor Karim.