To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: HIV Conquers Immune System Faster Than Previously Realised URL: http://www.pslgroup.com/dg/225FFE.htm Doctor's Guide July 18, 2008
DURHAM, NC -- July 18, 2008 -- New research into the earliest events occurring immediately upon infection with HIV-1 shows that the virus deals a stunning blow to the immune system earlier than was previously understood, according to a study in the August issue of Journal of Virology. According to researchers, this suggests the window of opportunity for successful intervention may be only a matter of days -- not weeks -- after transmission, as researchers had previously believed. This finding may make the challenge of designing an effective HIV/AIDS vaccine appear daunting. The study has also yielded a blueprint for what a successful vaccine should look like and, moreover, when such a vaccine would need to work. "This new study shows that HIV-1 does a lot of damage to the immune system very early in that time frame, and now we feel that the opportunity to intervene most effectively may range from about 5 to 7 days after infection," said senior author Barton Haynes, MD, Center for HIV/AIDS Vaccine Immunology, Duke University Medical Center, Durham, North Carolina. The findings suggest that an optimal vaccine strategy would have to pack a double punch by first establishing as much immunity as possible before infection and then by following a few days later with a mechanism to provoke a strong, secondary, broad-based antibody response, the authors wrote. "Vaccine candidates to date have pretty much followed a single strategy. Now we know that we need to activate multiple arms of the immune system, and we have a better idea of when to do it," said Dr. Haynes. The study included 30 people who were newly infected with HIV-1. Plasma from these individuals was sampled every 3 days for several months before, during, and after the "ramp-up" phase of infection. In measuring the levels of 4 products of CD4 T-cell death during this period in these samples, researchers were able to track and establish a timetable of the virus's destructive path. The 4 byproducts of CD4 T-cell death include tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), fas ligand, TNF receptor type 2, and plasma microparticles. The researchers found that TRAIL levels increased significantly a full week (7.2 days) before peak viral load, which is approximately 17 days after HIV-1 transmission. This suggests that during the eclipse phase, TRAIL may actually initiate or hasten HIV-1's destruction of CD4 T-cells. In contrast, investigators found that the levels of the other 3 cell death products were most significantly elevated during peak viral load. "What this demonstrates is that significant T-cell death is occurring much earlier during this period than we previously believed and that TRAIL itself may be a co-conspirator in enhancing cell death," Dr. Haynes said. "This leads us to believe that the time frame for successful intervention has to move even closer to the point of infection." Researchers also examined the effects of cell death products upon B cells through a series of in vitro laboratory experiments with peripheral blood cells and found that microparticles suppressed levels of immunoglobulin (Ig) G and IgA. "This is important because many scientists believe that a fast-acting memory B-cell response as well as a T-cell response will be necessary to fight HIV-1," said lead author Nancy Gasper-Smith, PhD, Duke University Medical Center. Daniel Douek, MD, Human Immunology Section, National Institutes of Health, Bethesda, Maryland, said the study sheds new light on key events in the earliest phase of infection. "The cohort is a gem. It is clear from the raised levels of TRAIL that the body senses the virus before plasma viral loads have peaked. This suggests that the virus begins to cause damage in ways that may be unrelated to the well-described massive depletion of gut CD4 T-cells that becomes apparent around peak viral load," said Dr. Douek. "For clinical practice, this means the window of opportunity in which antiviral therapies and vaccines must act is becoming ever narrower." "These and other studies … have given us valuable information that is helping us move closer to establishing a basic science foundation that can lead to novel technologies for vaccine design," said Dr. Haynes. "It is becoming clearer why we have failed in our efforts to date and what we need to confront to succeed in the future." SOURCE: Duke University Medical Center --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. 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