Pre-Human Immunodeficiency Virus (HIV) infection Th17 CD4 <sup>+</sup> T cells as predictors of early HIV disease progression
Notice bibliographique
Résumé
Abstract Interleukin-17-producing T helper (Th17) CD4 + T cells are highly susceptible to HIV infection and are depleted early in people living with HIV. Here, we investigated whether systemic Th17 cell levels prior to HIV infection are associated with subsequent HIV disease progression. We analyzed archived cryopreserved peripheral blood mononuclear cells (PBMCs) collected within one year prior to HIV acquisition from participants enrolled in a South African cohort (HIV Vaccine Trials Network [HVTN] 503; n = 35) and an East African cohort (Partners Pre-exposure Prophylaxis/Couples’ Observational Study [PP/COS]; n = 32). Th17 cell frequencies were quantified by flow cytometry. In HVTN 503, higher pre-HIV IL-17 + CD4 + T cell frequencies were inversely correlated with CD4/CD8 ratio measured both within 180 days (Spearman rank R = -0.42, p = 0.012) and beyond 180 days (R = -0.55, p = 0.001) after HIV infection, and were associated with faster CD4 + T cells decline (adjusted hazard ratio [aHR] = 3.5, 95% CI: 1.2-9.9, p = 0.020). In contrast, no significant association with CD4 decline was observed in the PP/COS cohort (HR = 1.2, 95% CI: 0.4–3.4, p = 0.795). Sex-stratified analyses in HVTN 503 indicated a more pronounced association between pre-HIV IL-17 + CD4 + T cells and faster CD4 decline in males than females. In analyses combining all cohorts, higher pre-HIV IL-17 + CD4 + T cell frequencies remained associated with faster CD4 decline, particularly among younger participants (HR = 3.5; 95% CI: 1.35-9.22, p = 0.010). Pre-HIV IL-17 + CD4 + T cell frequencies were not associated with peak or set-point viral load in either cohort. Together, these findings suggest that pre-HIV Th17 cells abundance may influence subsequent HIV disease progression independently of early viral replication. Author Summary HIV infection leads to progressive damage of the immune system, but the rate at which this damage occurs varies widely between individuals. Understanding the factors that influence HIV disease progression is essential for improving prevention and treatment strategies. Previous studies have suggested that immune characteristics present before infection may shape disease outcomes after HIV acquisition. In this study, we examined whether the abundance of IL-17-producing CD4 + T cells, known as Th17 cells, measured prior to HIV acquisition, were associated with markers of disease progression after infection. We analyzed blood samples from individuals who were HIV-negative at the time of sampling and later acquired HIV during follow-up. We found that individuals with higher pre-infection levels of Th17 cells experienced faster immune decline after HIV infection, including more rapid loss of CD4 + T cells and lower CD4/CD8 ratios. These associations were observed independently of viral load and varied by cohort, age and sex. Our findings indicate that immune conditions present before HIV infection can influence subsequent disease progression and suggest that Th17 cells may serve as biomarkers to identify individuals at higher risk of rapid HIV-related immune damage.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».