Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Apr 5;12(4):e0173893.
doi: 10.1371/journal.pone.0173893. eCollection 2017.

Impact of CD4 and CD8 Dynamics and Viral Rebounds on Loss of Virological Control in HIV Controllers

Free PMC article

Impact of CD4 and CD8 Dynamics and Viral Rebounds on Loss of Virological Control in HIV Controllers

Fanny Chereau et al. PLoS One. .
Free PMC article


Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control.

Methods: HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models.

Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds.

Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Fig 1
Fig 1. Cumulative incidence functions for loss of virological control, ART initiation and death since confirmation of HIV controller status.
Fig 2
Fig 2. Immunologic evolution during the last 5 years of HIV control according to the event ending virological control (in 794 HIV controllers with both CD4 and CD8 measurements during this period).

Similar articles

See all similar articles

Cited by 7 articles

See all "Cited by" articles


    1. Huang X, Lodi S, Fox Z, Li W, Phillips A, Porter K, et al. Rate of CD4 decline and HIV-RNA change following HIV seroconversion in men who have sex with men: a comparison between the Beijing PRIMO and CASCADE cohorts. J Acquir Immune Defic Syndr 2013;62:441–6. 10.1097/QAI.0b013e31827f5c9a - DOI - PubMed
    1. Hubert JB, Burgard M, Dussaix E, Tamalet C, Deveau C, Le Chenadec J, et al. Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group. AIDS 2000;14:123–31. - PubMed
    1. Cao W, Mehraj V, Kaufmann DE, Li T, Routy J-P. Elevation and persistence of CD8 T-cells in HIV infection: the Achilles heel in the ART era. J Int AIDS Soc 2016;19:20697 10.7448/IAS.19.1.20697 - DOI - PMC - PubMed
    1. Lambotte O, Boufassa F, Madec Y, Nguyen A, Goujard C, Meyer L, et al. HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin Infect Dis 2005;41:1053–6. 10.1086/433188 - DOI - PubMed
    1. Deeks SG, Walker BD. Human Immunodeficiency Virus Controllers: Mechanisms of Durable Virus Control in the Absence of Antiretroviral Therapy. Immunity 2007;27:406–16. 10.1016/j.immuni.2007.08.010 - DOI - PubMed

MeSH terms