Expanding HIV-Specific CD8 Cells Stifle HIV Reactivation in Elite Controller
Expansion of cytotoxic CD8+ T cells contributed to the rapid control of HIV reactivation in an elite controller who endured viral rebound immediately after myeloablation and autologous stem cell transplantation. The authors of the case study, which was published in the journal Clinical Infectious Diseases, believe this offers insights that may inform the development of a vaccine useful in HIV cure strategies.
Strategies aiming to cure HIV infection depend on reactivating and clearing latent virus secluded in resting CD4+ T cells. Some believe vaccination can play a role in such strategies by stimulating cytotoxic CD8+ T cells to help kill reactivated HIV. A rare opportunity to study viral reactivation and the CD8-cell response occurred in an elite controller who had long maintained an undetectable viral load without antiretroviral therapy.
The analysis involved a 59-year-old elite controller with refractory myeloma treated with melphalan (brand name Alkeran)-induced bone marrow cell destruction followed by autologous stem cell transplantation. The patient had never taken antiretrovirals, and antiretroviral therapy did not begin during the procedure. Six days after melphalan treatment, the patient's viral load rebounded from less than 50 copies/mL to 17,000 copies/mL; 13 days after melphalan treatment, the patient's viral load reached 28,000 copies/mL. The rebound doubling time of 0.5 days is similar to that observed in acute HIV infection (0.65 days).
After peaking around day 13, the patient's viral load dropped rapidly in a two-phase pattern with half-lives of 0.7 days and 4.1 days. The first and second phases of that decay are consistent with rates observed after potent antiretroviral therapy starts in a person with chronic HIV infection. Thirty-seven days after melphalan treatment began, the patient's viral load had again dropped below 50 copies/mL.
During the viral rebound, the investigators recorded increased frequencies of natural killer cell subsets and "striking expansion" of highly functional HIV-specific cytotoxic CD8+ T cells. Using a standard viral dynamic model, the investigators found that CD8-cell expansion in the patient reflected modeled gains in CD8 numbers as viral load waned to undetectability. The patient had a favorable response to the myeloma treatment.
These findings, the researchers proposed, "demonstrate for the first time that the human immune response is capable of controlling an iatrogenic large-scale HIV-1 reactivation, as might be induced by latency-reversing agents." They believe their data "suggest that the patient's HIV-1-specific CD8 T-cell response following [viral] reactivation directly contributed to the virus control observed." They proposed that vaccines capable of inducing "broadly functional" CD8-cell responses could prove effective in recognizing and clearing reactivated latent HIV.
Mark Mascolini is a freelance writer focused on HIV infection.