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Researchers Examine Immune Cells Where HIV Can Lie Dormant, Possible Treatments

February 4, 2008

Researchers have determined how HIV is able to lie dormant in certain immune system cells and prevent the cells from self-destructing, according to a study published Thursday online in the journal Retrovirology, the AP/ reports. HIV often resides in CD4+ T cells because the cells can survive for "years" or "even decades," according to the AP/ HIV also can lie dormant in macrophages, another immune system cell that attacks invading viruses or bacteria. Although macrophages are supposed to self-destruct if they are harmed, HIV is able to keep the cells alive past their typical lifespan, the AP/ reports.

For the study, Baek Kim from the University of Rochester and colleagues discovered that HIV produces a protein that initiates a specific cell-survival pathway. The researchers found that the protein ultimately triggers an enzyme, called Akt, that prevents macrophages from self-destructing and allows HIV to remain dormant. According to the researchers, it might be fairly straightforward to block the enzyme from hindering the cells' destruction, thereby eliminating the macrophage "hideout," the AP/ reports. The study also found that miltefosine, a drug currently used for leishmaniasis, can block the Akt pathway. Perifosine, a drug being studied as a possible cancer treatment, also blocked the enzyme's pathway, the study found.

Kuan-Teh Jeang -- an HIV specialist at NIH and editor-in-chief of Retrovirology who was not part of the study -- said, "Up to now, nobody has really thought about how to eliminate the macrophage reservoir," adding that the "imagination now has turned toward, 'How do we eliminate reservoirs?' ... The best way to address our problem is to simply kill those cells." Jeang noted that the evidence the researchers "show is in fact pretty good," adding that the next step should be to test miltefosine in monkeys infected with SIV. Kim said that he next plans to study the use of miltefosine in animals to determine if the drugs targets HIV-infected macrophages. "It's a very smart virus," Kim said, adding, "They have to have a very good fence to protect their house for a long time. ... Get rid of the fence, and now their house is gone" (Neergaard, AP/, 1/31).

Andrew Dayton of FDA's Center for Biologic Evaluation and Research in an accompanying commentary said the study's findings are "welcome news as delineating a possible novel therapeutic approach" to HIV. He added that the findings make "therapeutically attacking" the HIV macrophage reservoir a "tantalizing possibility" (Dayton, Retrovirology, 2/1).

Online The study is available online.

Online The accompanying commentary also is available online (.pdf).

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