No HIV-1 Reservoir Found in CD34+ Hematopotietic Progenitor Cells (HPCs)
A study published ahead of print in the Journal of Infectious Diseases fails to confirm the existence of an HIV reservoir in patients on cART in HPCs. These findings are important in defining which barriers are important to develop a cure against HIV infection.
Hematopoietic progenitor cells are a logical candidate for a second reservoir in addition to CD4+ T cells. In 2009, a team of reserachers was able to quantify HIV-1 DNA at this level in 4 out of 9 patients on effective cART (1).
More recently, at the "5th international Workshop on HIV Persistence during Therapy", Sarah Palmer et al did detect HIV in bone marrow but showed that it was related to T cell contamination. In fact, neither early nor late progenitors were infected in the bone marrow tissue of patients on long-term suppressive therapy treated during acute or late infection, indicating that progenitor cells in bone marrow are not a source of persistent HIV.
In the present study from R. Siliciano group (2), 11 patients on cART with plasma viremia <50 copies/ml for a median period of 4.8 years and a prior median nadir of 212 CD4 cells/mm3, were studied.
The authors used a rigorous purification technique leading to >98.7% purity of the CD34+ population and <0.2% CD3+ T cell contamination.
HIV-1 DNA was measured by real-time PCR with a limit of detection of 2 copies/105 cells.
A median of 5.5 x 105 CD34+ cells was assayed per patient. In all cases, no HIV-1 DNA was detected in sorted CD34+ cells. Coculture of cells from 7 patients with CD4+ lymphoblasts and cytokines failed to isolate infectious HIV-1.
In all cases, patients were infecetd by a subtype B HIV-1.
if these results are confirmed, they will facilitate the work towards an HIV cure...
1-Carter CC et al. Nature 2010; 16: 446-51
2-Durand CM et al. J Infect Dis 2012, Jan 24. [Epub ahead of print]. DOI: 10.1093/infdis/jir884
Key words: HIV CD34+ cells, HIV bone marrow, HIV hematopoietic progenitor cells, HIV reservoir