Major clinical outcomes in patients not treated with antiretroviral therapy (ART) at baseline in SMART; A rationale for a trial to examine early treatment of HIV disease
Reported by Jules Levin
4th IAS Conference, July 2007, Sydney, Australia
Sean Emery, Jacqueline Neuhaus, Andrew Phillips, Abdel Babiker, Calvin Cohen, Jose Gatell, Pierre-Marie Girard, Birgit Grund, Matthew Law, Marcelo Losso,
Adrian Palfreemen and Robin Wood for the SMART Study Group and INSIGHT.
--In early HIV disease, morbidity and mortality is probably higher than previously thought.
--Risk appears to be determined, at least in part, by time spent with lower CD4+ cell counts. (see graphs/tables below)
--The risk of OD and serious non-AIDS events is reduced by early versus deferred ART (a 5.7% reduction in absolute risk).
--The data require confirmation in a randomised clinical trial.
Cohort data describing morbidity/mortality in HIV disease
- Risk of AIDS persists for CD4+ >500 cells/mL1
- At any CD4+ cell count risk of AIDS is lower in ART treated patients2
- Risk declines following initiation of ART3
- Risk of serious non-AIDS disease (CVD, hepatic, renal) lower at higher CD4+ cell counts4-9
Strong associations between a modifiable risk factor (CD4+ count) and important clinical outcomes.
There are no high quality data with which to inform treatment decisions in patients with CD4+ cell counts higher than 350 cells/⊥
1. Cascade Collaboration. AIDS 2004
2. EuroSIDA. JID 2006
3. Egger M et al. Lancet 2002
Examine AIDS and non-AIDS outcomes in SMART not on ART at baseline.
The randomised comparison for these patients reflects immediate ART (> 350 CD4+ cells/⊥) versus deferred ART (<250 CD4+ cells/⊥).
Methods - patient population
1. Randomised in SMART
2. ART naive or
a). Not on ART at randomisation
b). > 1 plasma HIV RNA value in the 6 months prior to
c). All pre-randomisation HIV RNA > 10000 copies/mL
Methods - endpoint definitions
1. SMART primary endpoint (opportunistic disease (OD) and death)
2. OD (fatal and non-fatal)
3. Serious non-AIDS (CVD, hepatic and renal disease, non-AIDS cancers excl non-melanoma skin-cancers, non-OD deaths)
4. The composite of (2) and (3)
--Follow-up data until Jan 11, 2006 included.
--Time to first event described using Kaplan-Meier plots.
--Hazard ratio (95%CI) for Deferred/Immediate ART calculated using Cox models.
--For the composite endpoint we determined event rates and CD4+ cell count as a time-updated variable for comparison between Deferred and Immediate
4. DAD. CROI 2005
5. DAD. AIM 2006
6. Lau et al J AIDS 2007
7. DAD. CROI 2007
8. FIRST. CROI 2007
9. Cascade Collaboration. AIDS 2006