Rebound of Plama Viremia Following Cessation of Antiretroviral Therapy Despite Profoundly Low Levels of HIV Reservoir: implication for eradication
Chun TW, Justement JS, Murray D et al. AIDS 2010; 24: Oct. 19, Pub ahead of print.
The authors have analysed the 'residual' HIV-1 reservoir in 44 patients with long term ART-induced suppression of plasma viremia. They have measured both levels of proviral DNA in highly purified CD4+ T cells and infectious virus by high-input quantitative co-culture assays. Furthermore, HIV-1 DNA was also measured in gut biopsies taken from 2 patients. In one patient with extraordinarily low levels of the reservoir, ART was discontinued...
The study population included 44 patients who had received ART for a median of 7.7 years, including 9 during the early stages of infection (less than 6 months after acute infection). They were evaluated at least 3 times a year and did not experience any blip. HIV-1 DNA was measured with a technique having a limit of detection of 2.6 copies/microgram of genomic DNA (or 150,000 cell equivalent).
The median copy number of HIV proviral DNA for all study participants examined was 417.1 (range: <2.6 - 8804.4) per 106 CD4+ T cells. The median proviral DNA level in the study participants who had initiated ART within 6 months of acute infection was significantly lower (4.6 per 106 CD4+ T cells) compared to those who had initiated ART during chronic infection (949.4 per 106 CD4+ T cells), p=0.003. Of note, no measurable HIV proviral DNA was detected in four of nine early treated patients (44.4%) and four of 35 chronic treated (11.4%) individuals. However, in these 8 idividuals, infectious virus could still be recovered by co-culture.
Colonoscopy was performed in 2 individuals:HIV DNA was undetectable in one and at 89 copies per million cells in the other. ART was stopped in the patient with undetectable proviral DNA levels both in blood and rectum: plasma viremia was not detected for the first 50 days, then rebounded to 1593 copies/ml, became spontaneously undetectable at 10 days, and rebounded again at 8684 copies/ml. consequently, ART was resumed in this patient. This observation is intersting as , usually, plasma viremia rebounds after an average of 9 days following discontinuation of an effective regimen.
The paper conclusion is that early ART initiation provides a better reduction of the HIV reservoir after several years, but that additional strategies will be needed to eradicate this small residual disease.
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Key words: HIV, cure, eradication, persistence, proviral DNA, reservoir, reservoir, viremia rebound