Bad to the bone marrow?

The extent to which HIV may infect CD34+ hematopoietic progenitor cells (stem cells) in the bone marrow has been the subject of controversy for more than two decades. [1]

Early studies documented the presence of HIV in CD34+ cells in a subset of people with advanced disease, but a subsequent report offered little evidence of infection in asymptomatic individuals. [2]

In the new issue of Nature Medicine, a group of researchers from the University of Michigan revisit the issue in a paper that garnered substantial press coverage when it was released online a few weeks ago. [3]

The paper contains data indicating that CD34+ stem cells can be infected in vitro and also reports that HIV DNA could be detected in CD34+ cells sampled from the bone marrow of people with HIV infection, including four out of nine individuals on antiretroviral therapy (ART) with undetectable viral loads in peripheral blood. The researchers conclude that stem cells may be an important reservoir of latent HIV in people on ART.

There are some caveats, however, and it will be important for the findings to be confirmed (the researchers themselves acknowledge as much, stating: further studies are needed to show that CD34+ stem cells are infected). The in vitro work is primarily based on HIV isolates that are dual-tropic or target the X4 co-receptor, and the efficiency of infection by CCR5-using HIV appears lower (see the supplemental information panel a and compare the percentage of infected cells with the X4 and dual tropic viruses NL4-3 and 89.6 to the R5 viruses 94UG, MJ4 and YU2 [4]).

The numbers of individuals sampled for the in vivo results is also very small and analyses of larger cohorts are needed.

1. Stanley SK et al. CD34+ bone marrow cells are infected with HIV in a subset of seropositive individuals. J Immunol.1992; 149: 689-697.

2. Neal T et al. CD34+ progenitor cells from asymptomatic patients are not a major reservoir for Human Immunodeficiency Virus-l. Blood, Vol 86, No 5 (September l), 1995: pp 1749-1756.

3. Carter CC et al. HIV-1 infects multipotent progenitor cells causing cell death and establishing latent cellular reservoirs. Nat Med. 2010 Mar 7. [Epub ahead of print].