Direction at a glance
The ‘shock and kill’ family of strategies tries to expose latent proviruses and then remove infected cells. Research has increasingly shifted toward combination designs because latency reversal alone has not reliably reduced the intact reservoir.
What the evidence establishes
- The reservoir is biologically heterogeneous across cells and tissues.
- Viral transcription can be induced without eliminating the cell that contains the provirus.
- Reservoir assays must distinguish defective proviruses from replication-competent virus.
Next decisive research questions
Limits and responsible interpretation
What this direction does not yet prove
A change in one reservoir assay does not prove remission. Toxicity, tissue penetration and incomplete immune clearance remain central barriers.
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
NIH Strategic Plan for HIV and HIV-Related Research, updated 2025NIH Office of AIDS Research · Research strategy · Access checked 18 Aug 2026
↗02TGF-β blockade reverses SIV latency and decreases reservoirs in vivoNature Communications · Primary research · Access checked 18 Aug 2026
↗03ClinicalTrials.gov HIV study registryU.S. National Library of Medicine · Registry · Access checked 18 Aug 2026
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