May 12, 2015
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Human immune response may be able to control HIV-1 reactivation

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The human immune response appears capable of controlling coordinated, large-scale reactivation of the HIV-1 virus, according to recent findings.

Moreover, this immune response achieved virus control comparable to that of combination ART, the researchers wrote.

Nicola M.G. Smith, PhD, of Nuffield Department of Medicine, University of Oxford, and colleagues evaluated an elite controller with HIV-1, who underwent treatment for refractory myeloma with myeloablation and an autologous stem cell transplant. The participant was ART naive. After treatment, the patient experienced HIV-1 reactivation to 28,000 copies/mL at day 13.

The researchers used mathematical modeling to assess whether the patient’s usual HIV-1 kinetics and cell death rates were in accord with established models of cytolytic immune cell viral control. An enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining on peripheral blood mononuclear cells were collected at day 336. In vitro analysis also was conducted to quantify the ability of the patient’s CD8 T cells to limit virus production after infection of autologous T cells with an HIV laboratory isolate.

After the viral rebound, the investigators observed a rapid viral load decay of less than 50 copies/mL. This decrease followed two phases, the first with a half-life of 0.71 days and the second with a half-life of 4.1 days.

These HIV-1 kinetics were concordant with an augmentation of cytotoxic effector cells and destruction of productively infected CD4 T cells, the researchers reported. After transplantation, inherent immune cells, including natural killer cells, recovered with virus reactivation.

According to Smith and colleagues, the most noteworthy finding was the expansion of highly potent, HIV-1-specific cytotoxic CD8 T cells, at quantities in line with those applied in modeling, as virus control was recovered.

“The T-cell responses induced in this patient were typical of those induced in other elite controllers, suggesting that vaccination regimens that induce broadly functional CD8 T-cell responses, with good replicative potential and targeting conserved regions of HIV-1, might be more effective at recognizing and clearing reactivated HIV-infected cells,” the researchers wrote. – by Jen Byrne

Disclosures: Smith reports no relevant financial disclosures. One researcher reports receiving funding from Boehringer Ingelheim to attend conferences and receiving lecture fees from ViiV Healthcare, Gilead Sciences, and Janssen.