News From Baltimore: 13th IHV Meeting - Part I -
The Annual International Meeting of the Institute of Human Virology started on October 30, 2011.
We have selected for you some important presentations...
More than 350 International scientists are in Baltimore this week to attend the 2011 edition of Pr R. Gallo meeting.
Several presentations are devoted to HIV research, HIV prevention and care.
Among them, on this Sunday afternoon, we noted the lecture given by Robert Siliciano (*).
In his talk Siliciano asked the question whether ART was potent enough to completely block HIV replication and answered by using "pharmacomathematics". He recalled the work of Shen from his lab -published in 2008- on the dose response curve slope after log transformation as the ideal parameter. He argued that this parameter is directly linked to how many new infected cells arise in one viral generation. This is related to viral load and demonstrates that in average a potency of 6 log reduction is needed to block HIV replication. He now has used this parameter to calculate the potency of each available ARV. For some ARVs the response curve was linear, for others not. Protease inhibitors showed the highest inhibitory potential at clinical doses. That means that with increased dosage, the curve sharply increased. This was not observed with NRTIs or Raltegravir. The most effective P.I. was Darunavir/r, with up to 8-10 log reduction. Siliciano then tackled the issue of measuring the combined effect of drugs. With his model, he was able to evaluate the potency of more than 800 possible 3-drug combinations. Some regimens exhibited up to 12 log reduction due to a synergistic effect. He, however, concluded by saying that even the most potent of these regimens is unable, in his view, to influence HIV proviral reservoirs.
Another interesting presentation (**) this afternoon was on IL-7, given by Paolo Lusso (NIH). He first showed data proving that IL-7 decreases apoptosis in HIV infection. Then he moved to the effects of IL-7 administration AT ACUTE INFECTION in SIV-infected macaques. Twelve subjects were treated and no negative effect on SIV replication was observed. Depletion of central memory CD4 T cells and naive T cells were prevented by IL-7 but the effect was not long-lasting. Absolute increased of all CD8 T cell subsets was also observed. The CD4 protection was not due to increased proliferation but rather to a better resistance towards apoptosis (Bcl2 increase). Although the measure of apoptosis itself (Annexin V) was not conclusive in blood, it was significantly reduced in lymph nodes. He concluded that prolonged IL-7 treatment should be tested clinically in acute HIV infection. A participant asked if he had data on SIV reservoirs and he answered they were preliminary and did not show a trend.
This report is under the responsibility of its author. It does not stand as an official report from IHV or the concerned speakers. However, the author asked the 2 speakers if they agreed with it.
(*) Validation by the speaker is pending
(**) Report validated by the speaker
A second report will be published soon as an interview of Pr. Gallo focusing on the meeting main aspects.
Key words: HIV cure, HIV persistence, HIV reservoirs, R. Siliciano