Institutional members access full text with Ovid®

Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication

Chun, Tae-Wooka; Justement, J Shawna; Murray, Daniellea; Hallahan, Claire Wa; Maenza, Janineb; Collier, Ann Cb; Sheth, Prameet Mc; Kaul, Rupertc; Ostrowski, Marioc; Moir, Susana; Kovacs, Colinc; Fauci, Anthony Sa

doi: 10.1097/QAD.0b013e328340a239
Clinical Science

Objectives: Sustained suppression of plasma viremia in HIV-infected individuals is attainable with antiretroviral therapy (ART); however, eradication of virus that would allow discontinuation of ART has been hampered by the persistence of HIV reservoirs. It is of great interest to identify individuals who had received ART for prolonged periods of time with extremely low or undetectable HIV reservoirs and monitor plasma viremia following discontinuation of therapy.

Methods: We measured the size of HIV reservoirs in CD4+ T cells of individuals on long-term ART and monitored plasma viremia following cessation of ART in one individual with an exceptionally low viral burden after a decade of therapy.

Results: We demonstrated undetectable levels of HIV DNA in the blood of eight of 45 infected individuals on long-term ART. Among those eight individuals, the frequency of cells carrying infectious virus was significantly lower in those who initiated ART during the early versus the chronic phase of infection. One individual with undetectable HIV DNA in both blood and tissue and a profoundly low level of infectious virus experienced plasma viral rebound 50 days following discontinuation of ART.

Conclusions: Our data suggest that a significant reduction in the size of viral reservoirs may be achievable in selected individuals who initiate standard ART early in infection. However, given re-emergence of plasma viremia in an individual with an extraordinarily low viral burden, therapeutic strategies aimed at specifically targeting these extremely rare HIV-infected cells with novel interventions may be necessary in order to achieve eradication of virus.

aNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

bDepartment of Medicine, University of Washington School of Medicine, Seattle, Washington, USA

cDepartment of Medicine, University of Toronto, Toronto, Ontario, Canada.

Received 9 July, 2010

Revised 25 August, 2010

Accepted 8 September, 2010

Correspondence to Tae-Wook Chun, PhD, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 6A32, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel: +1 301 496 0890; fax: +1 301 402 5920; e-mail: twchun@nih.gov

© 2010 Lippincott Williams & Wilkins, Inc.