Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial)
2016
Piroth, Lionel | Moinot, Laetitia | Yeni, Patrick | Avettand-Fénoel, Véronique | Reynes, Jacques | Girard, Pierre-Marie | Marchou, Bruno | Georget, Aurore | Rouzioux, Christine | Autran, Brigitte | Duvillard, Laurence | Chêne, Geneviève | Fagard, Catherine | CHU Dijon ; Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon) | Agroécologie [Dijon] ; Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement | Epidémiologie et Biostatistique [Bordeaux] ; Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM) | Hôpital Bichat - Claude Bernard | Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327) ; Université Paris Descartes - Paris 5 (UPD5) | Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI) ; Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I (UY1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Cheikh Anta Diop de Dakar [Sénégal] (UCAD) | CHU Saint-Antoine [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) | Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades] ; Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Laboratoire de Virologie [CHU Necker] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Lipides - Nutrition - Cancer (U866) (LNC) ; Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA) | Laboratoire de biochimie médicale (CHU de Dijon) ; Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
International audience
Mostrar más [+] Menos [-]Inglés. The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count.ART-naive HIV-1-infected patients with baseline CD4 a parts per thousand yen500/mm(3) and nadir CD4 a parts per thousand yen400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118.The CD4 cell count remained a parts per thousand yen500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log(10) copies/10(6) leucocytes, PaEuroS=aEuroS0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections.In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.
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