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. 2010 Nov 27;24(18):2803-8.
doi: 10.1097/QAD.0b013e328340a239.

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

Tae-Wook Chun  1 , J Shawn Justement, Danielle Murray, Claire W Hallahan, Janine Maenza, Ann C Collier, Prameet M Sheth, Rupert Kaul, Mario Ostrowski, Susan Moir, Colin Kovacs, Anthony S Fauci
Affiliations

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

Tae-Wook Chun et al. AIDS. .

Abstract

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.

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Conflict of interest statement

Potential conflicts of interest: A.C.C. has received research grants from Boehringer-Ingelheim, Hoffman-La Roche, Gilead Sciences, Schering-Plough, and Tibotec-Virco, and consulted for Glaxo-Smith-Kline, Tibotec-Virco, and Pfizer.

Figures

Fig. 1
Fig. 1. Frequencies of HIV proviral DNA (a) and infectious virus (b) in CD4+ T cells of HIV-infected individuals receiving effective ART for prolonged periods of time
(a) Levels of HIV proviral DNA in highly enriched CD4+ T cells was determined by real-time PCR as previously described [10]. The open and closed squares represent data obtained from the ‘early treated’ and ‘chronic treated’ individuals, respectively. (b) Levels of replication-competent HIV in CD4+ T cells from infected individuals were determined by high input coculture assay as previously described [11]. The median is shown as gray bars.
Fig. 2
Fig. 2. Levels of plasma viremia following discontinuation and re-initiation of ART
Plasma viremia was determined by a branched DNA assay with the detection limit of 50 copies of HIV RNA per ml of plasma. ARV, antiretroviral.
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