Proviruses in CD4 <sup>+</sup> T cells reactive to autologous antigens contribute to nonsuppressible HIV-1 viremia
Bibliographic record
Abstract
Antiretroviral therapy (ART) halts human immunodeficiency virus–1 (HIV-1) replication, reducing plasma virus concentrations to below the limit of detection, but it is not curative because of a reservoir of latently infected CD4 + T cells. In some people living with HIV-1 (PLWH), plasma HIV-1 RNA becomes persistently detectable despite optimal ART. This nonsuppressible viremia (NSV) is characterized by identical, nonevolving HIV-1 RNA variants expressed from infected CD4 + T cell clones. The mechanisms driving persistent virus production from a specific population of infected cells are poorly understood. We hypothesized that proviruses in cells responding to chronic immunologic stimuli, including self-associated antigens, may drive viral gene expression and NSV. Here, we demonstrate that stimulation of CD4 + T cells with autologous cell lysates induced virus production in a major histocompatibility complex class II–dependent manner. In seven of eight participants with NSV, we recovered viral RNA released ex vivo in response to autologous cell lysates that matched plasma virus. This process involved both defective and replication-competent proviruses residing in conventional CD4 + T cells and was also observed in PLWH with undetectable viremia. These findings suggest that recognition of self-associated antigens is a potentially important cause of HIV-1 reservoir expression, which can contribute to persistent systemic inflammation and rebound upon ART interruption.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".