Viral Immunology Advances Suggest Treatment Strategies
A study published November 21 in Science1 is generating considerable scientific interest, and suggests possible treatment strategies for both early and more advanced HIV infection. While this study itself is one small building block among a number of important advances toward the understanding of how the body first controls HIV infection but later usually fails to do so, its publication seems to mark a time of change toward integration of virological and immunological approaches, away from the relative neglect of immunology and domination of HIV research by virology.The picture emerging from this and other studies is that in most cases of HIV infection, the T-helper cells which respond specifically to HIV (and help to bring down the very high viral load which develops during primary HIV infection) seem to be lost or stop working early in the disease process. The new study examined long-term nonprogressors, and found that in them, this specific T-helper response against HIV remained strong. In other persons with HIV who were tested, this response correlated strongly with low viral load (much more strongly than CD4 count correlated with viral load), suggesting that specific T-helper response to HIV is important in the body's control of the virus. Why the specific anti-HIV activity is lost is unknown; it is possible that the cells which recognize HIV are activated and therefore easily infected at the time of high viral levels during primary infection.
Two practical consequences have been suggested by a number of researchers:
(1) Effective antiretroviral treatment early enough--probably during primary infection with a regimen including protease inhibitors--may allow the specific anti-HIV responses to be preserved, as they seem to be in long-term nonprogressors. Early experience from treatment of patients during primary infection supports this possibility.
(2) Later in HIV disease, antiviral treatment which results in undetectable viral load generally does not lead automatically to the return of these specific anti-HIV T-helper cells. However, there is reason to believe that they still could be induced by vaccination while the infectious virus is suppressed by antiretrovirals. Several approaches--killed-virus vaccine, certain HIV antigens produced by genetic engineering, or DNA vaccines--are feasible to try now.
References
1. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, and Walker BD. Vigorous HIV-1-Specific CD4+ T Cell Responses Associated with Control of Viremia. Science. November 21, 1997, volume 278, pages 1447-1450. Also see commentary in the same issue, "How does HIV overcome the body's T cell bodyguards?," by Michael Balter, pages 1399-1400.
