January 31, 2001

STRUCTURED TREATMENT INTERRUPTIONS WORKSHOP

Workshop Summary

The investigation of Structured Treatment Interruption (STI) has fluid borders. Interruption is considered a treatment strategy per se, an adjunct to treatment, as well as the removal of treatment. Though first proposed as an immune-based treatment strategy, STI is now being explored as a research tool for basic science and clinical investigation, an option for clinical management, a tactic for toxicity relief, a way of reducing the cost of treatment, an aid to improving patient quality of life and as a method for guiding viral evolution. Recently, research on STI has begun as a resource conservation practice for large health networks or low-resource settings such as in developing countries. In addition, many clinicians and people on therapy have simply perceived a need to study the safety of what is already an established phenomenon — the “drug holiday.” Although fears about the danger of stopping treatment have been allayed and the popularity of treatment interruption has soared, there is still no firm consensus about the safety of STI.

The second STI Workshop assembled a diverse group of clinicians, researchers and community advocates from multiple disciplines. Investigator interest in structured treatment interruption is varied. Workshop attendees are leaders in exploring STI as a way to potentially enhance HIV-1-specific immune responses, limit drug exposure, prevent and recover from drug-related toxicity, allow a shift to a more drug-susceptible “wild type virus”(WT) in the absence of drug pressure, and improve quality of life for people with HIV. For two and a half days, participants candidly shared observations, data and speculation about the state and future directions of STI research.

The Workshop agenda was structured by presentations that addressed issues specific to these patient population categories: 1) primary infection, 2) chronic suppressed infection, and 3) chronic, unsuppressed drug resistant infection. A suite of Interlude Talks allowed participants to appreciate some interesting perspectives on new assays, mathematical modeling, insights from animal models and bench work. This was followed by a comprehensive overview of the immunologic, virologic and clinical hypotheses behind STI and the state of the evidence supporting them. Looking ahead, participants presented a range of new protocol designs. Finally, the meeting was summarized and task lists were drawn up.

Two years after news of the “Berlin Patient” launched the field, the promise of STI remains greater than its proven benefits. But this assessment varies by the population treated and by the benefit sought. Despite initial excitement about possible disease remission by STI-mediated immune control, it’s been the critical need for better quality-of-life while on long-term therapy that has driven the popularity of STI among patients.

STI as Treatment Research

• to stimulate response to autologous virus
• to boost after acute infection
• to boost after exogenous vaccine
• to relieve drug toxicity
• to limit drug exposure
• for improved quality of life
• until virus reverts to WT
• to suppress virus with fewer resources
• to reduce the cost of treatment

STI as Pathogenesis Research

• to elucidate science of immune response
• to elucidate viral and host immune dynamics
• to allow readout of clinical benefits from immune-based therapies