Intermittent viremia after treatment interruption increased risk of ART resumption in post-treatment HIV-1 controllers. ANRS VISCONTI study

Background: Some HIV-1-infected individuals achieve durable virological remission after discontinuation of antiretroviral therapy (ART). Because remission is a major objective in the global strategy towards an HIV cure, a better characterization of this phenomenon is necessary. We report here the long-term outcome of 23 post-treatment controllers (PTC) since their enrollment in a French study.
Methods: PTC were defined as HIV-1-infected individuals who achieved viral suppression (plasma viral load [pVL] < 400 copies/ml) for at least 12 months after treatment interruption. These cases have been prospectively followed in the ANRS VISCONTI study since 2008. Intermittent viremia was defined after treatment interruption as a transient pVL >400 copies/ml, and virologic failure (VF) as 2 consecutive pVL >400 copies/ml. Inflammation markers (IL-18, sCD14, CRP, IP-10, I-FABP and sCD163) were analyzed in plasma from 11 PTC at enrollment in the VISCONTI study.
Results: Twenty-three PTC (one case of mother-to-child transmission) were included, all of whom had started ART at the time of primary-infection (PHI). Main characteristics (median or %) at PHI were: age = 34 years, sex male = 65%, Caucasian = 70%, MSM = 48%, symptomatic PHI = 87%, pVL = 5.2 log copies/ml. ART was stopped after a median 3.7 years. Thereafter, PTC were followed-up for a median 11.9 years (until last visit or ART resumption). Overall, CD4 count and CD4/CD8 ratio were stable over time. Median total HIV-DNA was 1.85 log copies/106 PBMC at enrollment. Intermittent viremia was noted in 7 PTC (30%). Five patients (22%) resumed ART after a median 8.6 years off-ART: four because of VF, one for a non-AIDS defining cancer. Patients who had intermittent viremia were more likely to resume ART than those without: 5/7 versus 0/16, respectively (p=0.0006). PTC without intermittent viremia presented low levels of inflammation when compared to HIV controllers or HIV-infected individuals on ART (p< 0.05 for IL-18, sCD163 and sCD14).
Conclusions: Among PTC, one third presented an intermittent viremia after treatment interruption and were at increased risk of ART resumption. By contrast, the other PTC who had tighter control of viral replication maintained their status during follow up and had close to normal inflammation levels.

L. Hocqueloux1, V. Monceaux2, V. Avettand-Fènoël3,4, S. Orr5, F. Boufassa5, O. Lambotte6, T. Prazuck1, P. Miailhes7, D. Salmon8, C. Lascoux-Combes9, A. Lafeuillade10, L. Meyer5, M. Müller-Trutwin2, C. Rouzioux3,4, A. Saez-Cirion2, ANRS VISCONTI Study
1CHR d'Orléans - La Source, Infectious and Tropical Diseases, Orléans, France, 2Institut Pasteur, HIV Inflammation and Persistance, Paris, France, 3CHU Necker - Enfants Malades, APHP, Virology, Paris, France, 4Université Paris Descartes, Paris, France, 5INSERM CESP U 1018, University Paris Sud, APHP Bicetre Hospital, Le Kremlin-Bicetre, France, 6ImVA UMR 1184, Le Kremlin-Bicetre, France, 7CHU de la Croix-Rousse, Service des Maladies Infectieuses, Lyon, France, 8CHU Cochin, APHP, Service des Maladies Infectieuses, Paris, France, 9CHU Saint-Louis, APHP, Service des Maladies Infectieuses, Paris, France, 10Hôpital Général, Service des Maladies Infectieuses, Toulon, France