AIDS TREATMENT NEWS Issue #372, October 19, 2001
John S. James
Two independent studies published September 6, 2001, in the NEW ENGLAND JOURNAL OF MEDICINE(1,2) found that persons with HIV who were also infected with a virus not known to cause disease had a much lower death rate than those who were not infected -- with the risk of death being reduced about two to four times, depending on how the comparisons were done. The mechanism of this effect is not known, although there are some hints from laboratory studies. An accompanying editorial includes a warning against attempts to infect people deliberately, at least until more is known3.
The finding is not new; five early studies had reported a similar result, and one had failed to find it (that study was done differently); for references, see the Discussion section of the September 6 Tillmann paper2.
The virus, called GB virus C, is fairly common; it is found in about 1.8% of healthy blood donors, 15% of persons positive for hepatitis C, and up to 35% of persons with HIV3. This virus was first found in 1995, and is sometimes called hepatitis G virus, but that name is used infrequently since the virus does not appear to cause hepatitis or any other disease. Most people infected with GB virus C clear the infection normally; then they have antibodies, but no live virus can be found. Persons who have cleared the infection seem to have a somewhat reduced death rate from HIV, but not as much protection as those whose GB virus C infection is still active.
The importance of this finding is that it offers a window to a possible new understanding of HIV and a new way of controlling it.
HIV not only develops resistance to most drugs fairly rapidly; it also seems to evolve similarly to get around the patient's immune system. But GB virus C infection is associated with lower viral loads and improved survival even years later (although it is probably not associated with higher T-cell counts). If this virus is causing these effects, it is doing so in some way that HIV cannot easily evolve around.
Perhaps there is no causal relationship, and GB virus C infection gives no benefit but is only a marker for something already in the patient that is responsible for the better outcome. Even in this case there would still be an unknown mechanism in the patient that is not easy for HIV to evolve around, and that might be exploited to develop a new kind of drug treatment -- one probably closer to immune-based therapy than to traditional antiretrovirals.
The hardest kind of clinical trial to conduct is one that shows a survival benefit. Here we already have a clear survival benefit -- and thousands of patients who could be studied with nothing more intrusive than a blood draw.
1. Xiang J, Wunschmann W, Diekema DJ, and others. Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med 2001 Sep 6;345(10):707-14.
2. Tillmann HL, Heiken H, Knapik-Botor A, and others. Infection with GB virus C and reduced mortality among HIV- infected patients. N Engl J Med 2001 Sep 6;345(10):715-24.
3. Stosor V. and Wolinsky S. GB virus C and mortality from HIV infection. N Engl J Med 2001 Sep 6;345(10):761-2.
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