Suzanne Vernon: Negative results could indicate that assays are not sensitive enough. Positive controls and gold standards for XMRV detection in peripheral blood are needed.
CFS Central: In addition, Henrich and Barnes examined HIV patients for XMRV—and didn’t find it. There is significant evidence to suggest that infection with two retroviruses is unlikely, that infection with one retrovirus helps prevent infection by another, a phenomenon known as retroviral superinfection resistance (http://www.retrovirology.com/content/2/1/52). Would you comment on the possible role of retroviral superinfection resistance and negative XMRV findings in these patients?
Suzanne Vernon: The immune response to viruses that express similar antigens may help prevent dual infection. However, the role of superinfection resistance as it relates to XMRV has not been extensively explored.
CFS Central: Moreover, some of the HIV patients studied had been on ARV [antiretroviral] therapy. Do you believe being on ARVs could have made it more difficult to find XMRV in these patients?
CFS Central: Concerning the Henrich study, your article states that 32 patients met the Fukuda definition of CFS. However, in actuality these patients didn’t meet the Fukuda definition; they met the Empirical definition. The work of Dr. Leonard Jason has shown that 38 percent of patients who meet the Empirical definition actually have major depression. I think it’s an important point that Henrich is studying patients who don’t meet the Canadian or Fukuda definition, and who may be suffering from depression, not CFS. Would you explain your point of view concerning the CFS definition in this study?
Suzanne Vernon: Henrich et al used the 1994 CFS case definition criteria which is considered the revision of the 1988 CFS case definition published by Holmes. We have confirmed use of the 1994 criteria with the investigators. No one other than CDC has used the empiric approach in research.
CFS Central: You mentioned in your review that investigators should seek to replicate “as much as possible the features of the CFS patients found to be positive for XMRV and related MLVS in the studies published in Science and Proceedings of the National Academy of Sciences.” Shouldn’t a replication study replicate the patient group selected for the Science or PNAS studies precisely, by using the same definition—particularly in light of the divergent findings published and the resulting confusion that patients and researchers have been grappling with for a year? Thus, in these XMRV studies, shouldn’t patients meet the 1994 Fukuda definition and/or the Canadian definition of CFS, while weeding out the Empirical patients used in the Henrich study? Why or why not?