A 48-week course of antiretroviral treatment started within
six months of becoming infected modestly delays the need for lifelong treatment,
reported Dr Sarah Fidler of Imperial College, London, at the sixth
International AIDS Society conference (IAS 2011) in Rome.
Patients diagnosed with HIV infection fewer than 12 weeks
after exposure showed greater benefit from the 48-week course of treatment.
During the early days of highly active antiretroviral
therapy (HAART), Dr David Ho argued that treatment in primary infection might
offer an opportunity for eradicating HIV from the body, or at least drastically
limiting the damage caused to the immune system by HIV.
Subsequent clinical studies showed that early treatment did
not eradicate HIV, and that when treatment was withdrawn, HIV levels swiftly
rebounded to very high levels.
However, there has been continued interest in determining
whether a period of treatment soon after infection might limit damage to the
immune system and so delay the need for later lifelong treatment.
The SPARTAC study, led by Dr Sarah Fidler of Imperial College, London, compared three
strategies for dealing with primary infection:
- Begin treatment within six months of infection
and stay on treatment for 48 weeks (ART-48 arm).
- Begin treatment within six months of infection
and stay on treatment for 12 weeks (ART-12 arm).
- Do nothing except monitor the CD4 count and
health of the patient (standard of care, SOC arm).
The study sought to determine whether any of the strategies
reduced the risk of a CD4 decline to the level at which a person would normally
need to start treatment (< 350 cells/mm3). It also sought to
examine the effectiveness and tolerability of early treatment, the risk of drug
resistance, and the rate of CD4 cell decline in each group.
SPARTAC recruited 371 patients in the United Kingdom (40%),
Australia, Brazil, Ireland, Italy, South Africa (33%), Spain and Uganda.
All participants had verified infection with HIV-1 less than
six months before randomisation, defined as less than three Western Blot bands
and/or antibody-negative, PCR-positive infection. Five patients were
subsequently excluded from randomisation due either to incorrect diagnosis or to randomisation error.
Sixty per cent of participants were male, with a median age
of 32; 56% were gay or bisexual men. However, all South African participants were
women, so in effect, 96% of participants outside South Africa were male and 90%
were gay and bisexual men.
Participants had been infected for a median of 12 weeks at
the time of randomisation (range 9 to 15 weeks), and had a median CD4 count of 556
cells/mm3 and viral load of 4.53 log 10 copies (around
Participants were randomised equally to the three study arms
and followed for a median of 4.2 years. Ninety-one per cent of participants received a regimen of
AZT/3TC (Combivir) and
Approximately 6% of participants already had at least one drug resistance
mutation at baseline, suggesting that they had been infected with drug-resistant virus. Nucleoside analogue and non-nucleoside reverse transcriptase
inhibitor mutations were equally common (13 and 11 patients respectively).
After 4.5 years of planned follow-up, participants in the
48-week treatment arm had a significantly reduced risk of reaching a CD4 count
below 350 or needing to start long-term treatment (hazard ration 0.63, 95%
confidence interval 0.45 – 0.90, p=0.01) when compared to the standard-of-care
Participants in the 12-week treatment arm did not show a
significant reduction in their risk of CD4 decline or in their need to start
However, when the time taken to reach the primary endpoint
was compared, the average delay in the 48-week treatment arm when compared to
the standard of care was 65 weeks.
In other words, 48 weeks of treatment soon after infection
only delayed disease progression to the extent that a person treated soon after
infection would need four months less treatment during their life than someone
who didn’t take treatment immediately after infection.
But a secondary post hoc analysis showed that among people who started treatment in the 48-week
arm less than 12 weeks after becoming infected, there was a somewhat greater
reduction in the risk of disease progression (hazard ratio 0.48, 95% CI 0.30 –
0.78, p=0.003). Calculation of the subsequent
delay in starting treatment among this group of patients was not
Among those who started treatment more than 12 weeks after
infection, there appeared to be no significant difference in the risk of
disease progression between the standard-of-care group and the 48-week
This finding suggests that identifying very recent infection
will be critical if any benefit of an early course of treatment is to be
Short courses of treatment may carry risks however. While early treatment could limit the size of
the viral reservoir, removal of treatment would allow the viral reservoir to
swiftly expand. Stopping treatment might also cause inflammatory changes that
would increase the risk of other serious, non-AIDS defining illnesses.
However, patients in the 48-week treatment arm of the
SPARTAC study continued to have lower levels of viral load than untreated
patients in the control arm for at least 60 weeks after stopping treatment, and
their average CD4 cell count remained 135 cells/mm3 higher than the control arm
after 4.5 years follow-up. But the rate of decline of CD4 count did not differ
between the treatment arms and the standard-of-care arm.
Levels of the inflammatory markers IL-6 and d-dimer did not
go up after treatment interruption, unlike in the SMART study of treatment
There was no difference in the rate of serious adverse
events between patients in the treatment arms and patients in the standard of