December 18, 2012
During ICAAC 2012, researchers in France presented data that provided a potential explanation for why some patients have a persistently low CD4+ cell count despite being virally suppressed.
The researchers used a qPCR assay to look for HIV DNA in the CD4+ cell cytoplasm, which has a short half-life and could be a reliable marker of recent CD4+ cell infection. Of the 35 study participants, 10 were found to have HIV DNA in the CD4+ cell cytoplasm. Average CD4+ cell counts for these 10 individuals were lower than the rest of the group, suggesting that ongoing HIV infection could be responsible.
This simple assay could help assess how well antiretroviral drugs are working for patients, and may help clinicians determine which patients may need stronger regimens.
In the wake of CROI 2012, Jeff Berry reported on the HIV drugs that were at the front of the antiretroviral pipeline. In a phase-3 study, the once-daily regimen elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild), also known as the "Quad," was found to be non-inferior to efavirenz/tenofovir/emtricitabine (Atripla) after 48 weeks. (It was approved by the U.S. Food and Drug Administration later in 2012.)
Berry covered other drug developments in the article, including phase-2b study results of the new integrase inhibitor doultegravir, which was shown to be superior to efavirenz (Sustiva), with no emergent resistance mutations after 96 weeks.
During the XIX International AIDS Conference, a study published in Nature highlighted the apparent ability of a histone deacetylase (HDAC) inhibitor known as vorinostat to disrupt the HIV reservoir. The results showed that when eight patients, all of whom were already on antiretroviral therapy, received vorinostat, HIV was flushed out of the hidden reservoir -- at least for a moment.
Co-author David Margolis, M.D., stated during an interview at the International AIDS Conference, "This is proof of the concept, of the idea that the virus can be specifically targeted in a patient by a drug, and essentially opens up the way for this class of drugs to be studied for use in this way."
At the first-ever IDWeek, Joseph Eron, M.D., director of the University of North Carolina Center for AIDS Research, provided an overview of current HIV cure research. He highlighted the three "functionally" cured patients of which we are currently aware (more on two of those patients in a moment), all of whom serve as proof of concept.
While Eron pointed out the barriers that block us from a practical cure, he also discussed the potential cure strategies being developed. These include targeting the HIV reservoir with HDAC inhibitors such as vorinostat, artificially disrupting the CCR5 receptor on CD4+ cells using zinc finger nucleases, and other areas currently under investigation.
During the XIX International AIDS Conference, case results were presented that suggested two more individuals had potentially been cured of HIV. Daniel Kuritzkes, M.D., from Brigham and Women's Hospital in Boston discussed the promising method that led to the results, which targeted the elusive HIV reservoir.
Two patients had undergone allogeneic stem cell transplantation for the treatment of lymphoma. Unlike "Berlin patient" Timothy Brown, their donor cells did not lack the CCR5 receptor and were fully susceptible to HIV. But because they remained on antiretroviral therapy during the transplant period, the donor cells were not infected with HIV.
Although both men are still on HIV treatment, neither shows traces of HIV in his blood. They are also showing a significant decline in HIV antibodies, suggesting a lack of HIV replication.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
Follow Warren on Twitter: @WarrenAtTheBody.
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