Greetings from Washington DC. Nice to be back. I used to live here and went to George Washington University as an undergraduate. I couldn’t understand why all the guys at University wore pink cashmere jumpers and tartan trousers until a friend from Australia sent me a book on ‘Preppies’.
Today we had a retrospective symposium on SMART: “Five Years after the SMART study, a Paradigm-shifting Trial” (SUSA56)
Some of the speakers’ points are outlined below
Tony Fauci opened the Symposium noting that SMART one of the most influential trials in HIV medicine, that it helped us understand the importance of chronic immune activation and coagulation in HIV disease and, finally, that it was the result of major collaborative efforts.
Wafaa El-Sadr reflected on HIV Treatment Research in 2002
She reflected on the background to the SMART study: the idea was conceived in her apartment in New York city one evening with Jim Neaton, Fred Gordin and Birgit Grund.
- The impact of SMART was to immediately change guidelines such that treatment interruptions were not recommended at a guideline level
- Objective evidence of SMART’s impact upon treatment patterns comes from an analysis of the Royal free database: after SMART the percentage of people using intermittent ART decreased from 5-6% to 2%-3%.
- A paradigm shift occurred as a result of SMART vis-a-vis a greater understanding of the pathogenesis of HIV disease.
- With all the bio specimens that were collected in SMART it created the opportunity to engage with non-HIV doctors who became interested and utilized the samples from SMART in collaboration with SMART investigators => excellent synergies from working with people outside of the HIV field
Wafaa’s final slide noted
- SMART challenged the status quo
- Getting an unexpected answer to a question is often more profound than getting the expected answer
- Seeking definitive answers to tough questions is not easy, requires patience and may be costly but is well worth it
- Other tough questions of the hour remain that will have to be answered
Andrew Wilson addressed HIV Treatment Research Post SMART
- That SMART was the first trial that used serious non-AIDS events as a major trial endpoint
- That 92% of all deaths in SMART were serious non-AIDS events
- Clinical event risk at high CD4 count range are nearly all related to non-AIDS conditions - these events were not being collected in most HIV cohort studies at the time
- The key question is what is the ongoing excess risk of morbidity due to HIV in people with successful viral suppress on compared to HIV negative controls ART
Jens Lundgren addressed why the START trial is necessary and how it stands on the shoulders of SMART
He posited that one must consider the case that START may show early ART is harmful and he invoked the physician’s creed: Primum non nocere (first do no harm).
This argument runs as follows:
- Morbidly and mortality in early HIV in young persons are LOW
- ART may adversely effect a variety of organ functions
- If this scenario turns out to be correct we will know whether early ART is harmful within 3 years
- Jens also noted that only 3 RCTs had addressed early versus deferred ART: The Haiti trial (NEJM 2010), the SMART subgroup (JID 2008) and HPTN 052 (NEHM 2011) but none of these used the same CD4 criteria as START
- He also noted that 4 observational studies had addressed early versus deferred ART: When to start, NA ACCORD, Causal collaboration and CASCADE
- However using the GRADE classification (see www.gradeworkinggroup.org) these studies would be graded as C whereupon a score of A is best
It was an excellent retrospective.