Although combined antiretroviral therapy (cART) is able to achieve sustained control of viral replication in blood plasma and to significantly reduce HIV-associated mortality and morbidity, it cannot, to date, yield viral eradication. Indeed, during the earliest phases of primary HIV infection (PHI), HIV establishes a reservoir in its target cells, particularly in the CD4+ memory T-cell subsets [1, 2]. The half-life of these latent cells can reach up to several years and supplies to the persistence of the infection. cART has small or no impact on this cellassociated HIV-DNA (CA-HIV-DNA) even after several years of sustained viral suppression [3, 4]. In addition, anatomical sites, such as the male genital tract [5, 6] and the central nervous system [7], may also act as viral sanctuaries, contributing to HIV persistence despite cART, partly because of the poor penetration of antiretroviral drugs in these anatomical compartments [8]. Thus, cART is a life-long treatment for people living with HIV (PLHIV). Although new generation antiretroviral drugs are more potent, better tolerated, and with a lower pill burden, concerns still remain about long-term toxicity of these drugs, the need for long-term adherence to cART to avoid the emergence of HIV resistance, and cost issues, especially in low-income countries with a high prevalence of PLHIV. Thus, one of the major goals of researchers in the field of HIV infection is the evaluation of new strategies to achieve a cART-free remission of HIV infection. In this issue, Li et al.[9] address the critical roles of treatment interruption studies and biomarker identification in the search for an HIV cure. Achieving HIV eradication or at least a cART-free remission has been indeed priority issue in the research field of HIV infection since the last decade. HIV cure has been achieved in one single case, in the Berlin patient [10]. This patient remains free from HIV in blood plasma as well as in HIV target cells and in anatomical compartments several years after cART discontinuation following two total body irradiations and two allograft marrow transplantations from a donor who was homozygous for CCR5 Δ32 deletion [11]. Unfortunately, such a cure strategy did not prove to be reproducible to date, particularly with graft from donor with wild-type CCR5-positive cells [12, 13]. There are two other populations of PLHIV that achieved HIV remission: the HIV controllers, who control spontaneously viral replication [14] and the posttreatment controllers (PTC), in whom cARTwas initiated early during PHI, and who were subsequently able to control viral replication for several years after cART interruption [15]. The first population exhibits specific host genetic and immune features, whereas the latter population does not [15, 16]. Finally, a small proportion of patients treated during chronic infection was also able to achieve cART-free remission [17]. The only way so far to identify PTC or PLHIV able to achieve such a cART-free remission is through cART interruption. aUnité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre Hospitalier Universitaire Hôtel Dieu, Hôpitaux de Paris, bNecker School of Medicine, Paris Descartes University, Sorbonne-Paris-Cité, cLaboratoire de Virologie, Hôpitaux de Paris, Hôpital Saint-Louis, dUniversité Paris Diderot, Sorbonne Paris Cité, and eINSERM U941, Hôpital Saint-Louis, Paris, France. Correspondence to Dr Jade Ghosn, MD, PhD, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre Hospitalier Universitaire Hôtel Dieu de Paris, 1 Place du Parvis Notre Dame, 75004 Paris, France. Tel:+ 33 1 42 34 88 36; fax:+ 33 1 42 34 88 52; e-mail: jade. ghosn@ htd. aphp. fr Received: 22 March 2015; revised: 28 May …