Discovery of ‘Reservoir’ that Helps HIV Hide Dims Hope of AIDS Cure

Research by Dr. Robert Siliciano of Johns Hopkins University showing that HIV invades and hides in "resting memory T cells" -- long-living immune cells that record the germs the body encounters and then go latent -- has "shifted the ultimate goal" of HIV/AIDS treatment from annihilation to control of the virus, the AP/Richmond Times-Dispatch reports. HIV's "primary target" is CD4+ T cells, white blood cells that the virus "hijacks" in order to replicate itself. While these cells usually die after replication, a few survive and become memory T cells. The memory cells are not targeted by the antiretroviral drugs because they appear "perfectly normal," with the only difference between latent HIV-infected cells and regular memory cells being "a little bit of HIV DNA," Siliciano said. In 1997, Siliciano and two other research teams discovered HIV in the memory cells of patients who had been "seemingly free of the virus for two years." Despite undergoing antiretroviral therapy, the patients in the studies had "fully potent copies of [HIV] inside their memory cells" (Haney, AP/Richmond Times-Dispatch, 4/29). Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said that the discovery was a "sobering realization about the recalcitrant nature of this reservoir."

The Life of a Memory Cell
The discovery was "disturbing" because little is known about memory cells' lifespan and whether they can be eradicated. Memory cells are "programmed to do nothing but sit and wait" for viruses to attack, their "only job" being to keep a record of the germs that the body has previously encountered so that the immune system will be ready the next time it is confronted with the antigens. "What HIV has done is tap into the most fundamental aspect of the immune system, and that is [a person's] immunological memory. It's the perfect mechanism for the virus to ensure its survival," Siliciano said (AP/San Diego Union-Tribune, 4/28). Because the cells are the immune system's memory, they must survive for a long time, creating a "latently infected reservoir" of HIV in the body. This reservoir is the "single biggest obstacle to getting rid of AIDS," scientists say. "It's the thing that keeps us from curing this," Dr. Roger Pomerantz of Thomas Jefferson University in Philadelphia, said (AP/Arizona Daily Star, 4/29). "We are not going to be eliminating this reservoir. Whether you can measure it or not doesn't seem to have a significant impact on the clinically relevant phenomenon of what happens when you stop the drug," Fauci said (AP/Charlotte Observer, 4/29).

Testing New Attack Plans
Scientists have tried to destroy the latent T cells, first by "flush[ing]" the body with the immune modulator interleukin-2, which they hoped would "awaken" and then kill the dormant cells. Biopsies of patients' lymph nodes taken during this research originally found no trace of the virus, but within three to four weeks after ceasing treatment, the virus reappeared in every patient. Scientists have developed two competing theories as to why the memory cells persist. The first, favored by Siliciano, says that the "basic biology" of the cells programs them to last for a lifetime, which explains why childhood diseases do not resurface in adulthood (AP/Akron Beacon Journal, 4/29). Although memory cells die, the rate at which they die is very slow. Siliciano estimates that even with the drugs available today, it would take 73 years for the memory cells to completely die off (AP/Arizona Daily Star, 4/29). A second theory postulates that the supply of memory cells is "constantly replenished." Dr. David Ho of the Aaron Diamond AIDS Research Center in New York says that the cells are much "shorter-lived" and renew their supply through cell division due to a "continuing cycle of low-level infection." Ho's team is conducting a study that attempts to shrink or destroy the reservoir by stopping the "residual replication" of the memory cells through a four-drug combination therapy. Thirty patients are currently taking the drugs in hopes of halting the "low-level circulation" of HIV, thereby "shut[ting] off the supply of newly infected memory cells." If the approach proves successful, Ho thinks it could eradicate the HIV-infected memory cells within three to four years (AP/Akron Beacon Journal, 4/29). Researchers are also concerned that HIV may reside in other "long-lived reservoir[s]" in places like the brain, bone marrow and testes. "It will be a daunting task to eliminate those unknown viral reservoirs, even with much more potent drugs that might come out in the near future," Dr. Tae-Wook Chun of NIAID said (AP/Detroit News, 4/29).