A Community Perspective on SMARTRichard JefferysCoordinator, Michael Palm Basic Science, Vaccines & Prevention Project

Historical, Personal PerspectiveAIDS Treatment Data Network, NYC: Provided low

literacy treatment information (Simple Fact Sheets), NY State clinical trial directory, State ADAP & Medicaid database, NY State ADAP drug guide. National & State toll-free numbers. ~3,000 members

Post-1996, decline in calls for information & referrals, but population calling were those struggling the most with ARVs

Not surprisingly, great deal of interest in results of small trials suggesting CD4-guided ART interruption was safe

Bias toward assuming CD4-guided ART would be equivalent or superior to continuous

Broader Community Interest in Treatment InterruptionsStructured Treatment Interruptions (STI) Workshop, July

30-August 1, 1999, Boston – co-sponsored by the Foundation for AIDS & Immune Research (FAIR), Project Inform and Treatment Action Group (TAG)

2nd STI Workshop, October 13-15, 2000, Boston - FAIR, the Forum for Collaborative HIV Research, Project Inform and TAG

3rd International STI Workshop, March 23-24 2002, Montreal - FAIR, the Forum for Collaborative HIV Research, Gay Men's Health Crisis, Project Inform and TAG

Community Support for Large Simple TrialsRescuing Accelerated Approval: Moving Beyond the

Status Quo by Spencer Cox, Dennis Davidson, Gregg Gonsalves, Mark Harrington, Carlton Hogan, Rebecca Pringle Smith, September 12-13, 1994 A Rationale for Large Simple Trials in AIDS by Carlton

Hogan, PWA Alive and the University of Minnesota

CPCRA 065: A Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)

SMART Results Jan 23, 2006 Clinical Alert: International HIV/AIDS Trial

Finds Continuous Antiretroviral Therapy Superior to Episodic Therapy

Response: Denial

Something wrong with the data Anger

It’s a pharmaceutical boondoggle Bargaining

Maybe interruptions worked for some people (quality of life?)

Depression

Acceptance Immune activation=inflammation (not just T cell

markers) Inflammation=physiological harmAbility of ART to prevent AIDS allows time for

consequences of inflammation to manifestMany assumptions about role of drug toxicity were

wrongLarge simple trial design was critical in revealing what

smaller trials could notUnquantifiable amount of harm averted due to impact

of the results on clinical trial designs and care

Future Need for LSTs?Community concern regarding immunological non-

responders, and need to conduct clinical endpoint trials of interventions in this population

Adjuncts to ART, perhaps particularly in the aging HIV+ population e.g. anti-inflammatories

How will such trials be conducted & funded?

Carlton Hogan, 1961-2003

Linda Grinberg, 1951-2002