Direction at a glance
Block-and-lock strategies seek to place persistent HIV into a deeper, durable transcriptionally silent state so that rebound remains suppressed without continuous ART, even if every provirus is not removed.
What the evidence establishes
- Some proviruses remain transcriptionally active during suppressive ART.
- HIV Tat and host transcriptional machinery offer targets for deeper silencing.
- Durable silence must be tested after drug removal and across heterogeneous integration sites.
Next decisive research questions
Limits and responsible interpretation
What this direction does not yet prove
Most evidence remains preclinical or mechanistic. Silencing is not eradication, and rare rebound-competent cells may still matter clinically.
Development pathway
| Decision | Required evidence |
|---|---|
| Biological activity | Target engagement and an outcome that cannot be explained by assay noise or selection. |
| Clinical value | Meaningful benefit, adequate follow-up, safety, comparison with current standard care and transparent uncertainty. |
| Generalizability | Diverse populations, subtypes, geographies, ages and clinically relevant comorbidities. |
| Scalability | Manufacturing, delivery, monitoring, price, workforce and community acceptability. |
Principal sources and evidence gateways
Links checked 18 August 202601
Silencing the transcriptionally active HIV reservoirNature Microbiology · Primary research · Access checked 18 Aug 2026
↗02NIH Strategic Plan for HIV and HIV-Related Research, updated 2025NIH Office of AIDS Research · Research strategy · Access checked 18 Aug 2026
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