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Continuous versus intermittent treatment strategies during primary HIV-1 infection: the randomized ANRS INTERPRIM Trial

Goujard, Cécilea,b; Emilie, Dominiquec,*; Roussillon, Carolined,e; Godot, Véroniquec; Rouzioux, Christinef; Venet, Alaing; Colin, Célined,e; Pialoux, Gillesh; Girard, Pierre-Mariei; Boilet, Valéried,e; Chaix, Marie-Lauref; Galanaud, Pierrec; Chene, Genevièved,e,j; for the ANRS-112 INTERPRIM Study Group

doi: 10.1097/QAD.0b013e32835844d9
Clinical Science

Objectives: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI).

Design and methods: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption.

Results: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4+ T-cell counts and CD4+ T/CD8+ T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4+ T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups.

Conclusion: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.

aService de Médecine Interne, Hôpital Bicêtre, Assistance Publique – Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre

bINSERM U1018, CESP, Université Paris-Sud 11, Le Kremlin Bicêtre

cINSERM U996, Université Paris-Sud 11, Clamart

dINSERM, ISPED, Centre INSERM U897-Epidémiologie-Biostatistiques, Bordeaux

eUniversity Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistiques, Bordeaux

fLaboratoire de Virologie, Hôpital Necker-Enfants Malades and EA-MRT 3620 Université Paris Descartes, AP-HP, Paris

gINSERM U1012, Université Paris-Sud 11, Le Kremlin Bicêtre

hService de Maladies Infectieuses, Hôpital Tenon, AP-HP, Paris

iService de Maladies Infectieuses, Hôpital Saint Antoine, AP-HP, Paris

jCHU de Bordeaux, Pole de Sante Publique, Bordeaux; France.

*Dominique Emilie died in an accident in 2011 and could not achieve the preparation of this article. This work is dedicated to his memory.

Correspondence to Professor Cécile Goujard, Hôpital Bicêtre, AP-HP, Le Kremlin Bicêtre, Cedex, France. Tel: +33 1 45 21 23 25; fax: +33 1 45 21 79 34; e-mail: cecile.goujard@bct.aphp.fr

Received 21 April, 2012

Revised 16 July, 2012

Accepted 18 July, 2012

© 2012 Lippincott Williams & Wilkins, Inc.