Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial)

Abstract : 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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Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2016, 71 (2), pp.490 - 496. 〈10.1093/jac/dkv369〉
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Contributeur : Lnc - Université de Bourgogne <>
Soumis le : jeudi 6 avril 2017 - 18:11:26
Dernière modification le : mercredi 24 janvier 2018 - 01:02:02

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Lionel Piroth, Laetitia Moinot, Patrick Yeni, Véronique Avettand-Fénoel, Jacques Reynes, et al.. Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial). Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2016, 71 (2), pp.490 - 496. 〈10.1093/jac/dkv369〉. 〈hal-01503254〉

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