Single-cell multi-omics study maps immune failure in HIV non-responders
A preprint from Cold Spring Harbor Laboratory profiles nearly 2.7 million transcriptomes to characterise why some people living with HIV fail to recover immune function despite antiretroviral therapy.
A preprint posted to bioRxiv by researchers at Cold Spring Harbor Laboratory reports large-scale single-cell multi-omics profiling aimed at understanding immune reconstitution failure in people living with HIV (PLWH). A subset of PLWH — termed immune non-responders (INRs) — fail to achieve adequate CD4+ T-cell recovery after antiretroviral therapy and remain at elevated risk of morbidity and mortality from both AIDS-related and non-AIDS-related illnesses. The mechanisms underlying this impaired recovery have remained poorly understood.
The study profiled peripheral blood mononuclear cells from 43 INRs, 47 immune responders, and 53 healthy donors, generating 2,744,009 transcriptomes and 1,226,658 chromatin-accessibility profiles across 58 identified immune cell types. This makes it one of the larger single-cell datasets applied to this clinical question to date. Reported findings include markedly elevated inflammatory signalling in INRs relative to both immune responders and healthy donors, though the full dataset and conclusions are available only in the preprint.
The work is relevant to researchers in HIV immunology, genomics, and single-cell methods, as well as those with interests in chromatin accessibility and transcriptional regulation in immune disease contexts. As a preprint, it has not yet undergone peer review, and findings should be treated as preliminary.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Researchers have published early-stage findings — not yet formally peer-reviewed — looking at why some people living with HIV do not fully recover their immune system even when they are taking effective antiviral medicines. This failure to recover immune cells is known as immune non-response, and it leaves some people at higher risk of illness.
To investigate this, the research team analysed blood samples from over 140 participants, using a technique called single-cell multi-omics that can examine millions of individual cells and measure how genes are switched on or off in each one. They found signs of unusually high levels of inflammation in the cells of people whose immune systems had not recovered well.
This is early research and the results have not yet been checked through the standard scientific peer-review process, so they may change. The study does not offer any new treatments or immediate changes to care.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
Read the original reporting — these are the public sources this summary draws from.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-23Decoding Immune Reconstitution Failure in People Living with HIV through Single-cell Genomics