Antiretroviral therapy initiated during acute infection in women with HIV-1 clade C reduces anti-Tat antibody production and lowers CD8+ T cell activation
Bibliographic record
Abstract
Introduction: The HIV-1 Tat protein is essential for virus replication and spread and is therefore a potential target for anti-HIV therapy. Anti-Tat antibodies have been shown to slow HIV disease progression and improve antiretroviral therapy (ART) efficacy. Long-term ART results in partial reconstitution of the immune system in people living with HIV-1 (PLWH) who start treatment in the chronic phase of infection, but the impact of ART initiation in the acute phase of infection is less studied. In this study, we investigate the effect of initiating ART in acute phase infection on the production of anti-Tat antibodies and on T-cell activation. Methods: Anti-Tat IgA, IgG, and IgM titres were evaluated longitudinally by enzyme-linked immunosorbent assay in plasma samples collected from 34 women who started ART immediately following the detection of acute HIV-1 infection. Total HIV-1 DNA measurements were performed by droplet digital PCR from total peripheral blood mononuclear cells at 1-year post ART initiation. T-cell activation was assessed longitudinally by analysis of the expression of HLA-DR and CD38 on CD4+ and CD8+ T-cells using flow cytometry. We also explored the association between anti-Tat antibody titres and CD4+ T-cell counts. Results: The data showed that anti-Tat IgG and IgM titres had decreased significantly after 12 months of treatment (p=0.0001) with no correlation between anti-Tat IgA, IgG or IgM and CD4+ T-cell counts (r= -0.09 to 0.2, p>0.05). There was no correlation between anti-Tat antibody levels and total HIV-1 DNA levels at ART initiation (r= 0.2143, p= 0. 6191) or after 12 months post-ART (r= -0. 2857, p= 0, 5008). There was a significant decrease in CD8+ T-cell activation between the baseline (day 1 on ART) and 12 months post-ART (p=0.0129). Discussion and conclusion: These findings suggest early initiation of ART reduces the production of anti-Tat antibodies and reduces CD8+ T-cell activation. Further studies on the impact of early ART on antiviral immune responses are needed and may shed light on mechanisms of optimal immune reconstitution and reservoir control in PLWH.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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 source (direct Gemma or distilled Codex), 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".