The annual Conference on Retroviruses & Opportunistic Infections (CROI) was held last week in Montreal. Although CROI has taken flak over the years for having strict registration policies, it also deserves credit for offering the most comprehensive web coverage of any conference. In addition to webcasts of every session except poster discussions, pdf files of poster abstracts are also rapidly placed online on the conference website.
Among the highlights this year were results from a phase 2B study of the microbicide PRO2000/5 gel which offered encouraging evidence that the product might prove efficacious in a large ongoing phase III efficacy trial. The phase 2B results showed around 30% efficacy and just failed to reach significance, but multiple analyses appeared consistent with the product having some protective effect. Results from the phase III trial are expected before the end of 2009. The presentation of the data was by Salim Karim and his talk is the fourth presentation in the webcast of the “HIV Transmission: Characteristics and Prevention” session.
In vaccines, Phil Johnson described experiments designed to establish whether AAV vectors could be used essentially as gene therapies. Johnson has produced AAV constructs that encode and persistently express monoclonal antibodies capable of neutralizing SIV, and he showed at CROI that this approach protected three animals from SIV infection in preliminary challenge experiments. David Watkins also presented results from a study in which macaques that received a multi-antigen SIV vaccine were challenged with a heterologous virus, SIVsmE660. The degree of control of both peak and set point viral loads was unusually robust. Both of these talks can be viewed in the webcast of the Wednesday vaccine symposium.
One area of concern highlighted by CROI is the accumulation of data showing that a significant subset of individuals receiving HIV treatment remain at risk for clinical illness due to suboptimal immune reconstitution (despite effective viral suppression). A low nadir CD4 count prior to starting treatment appears to be the single largest risk factor, but other variables such as age and thymic function also appear to be involved. Many studies have now reported that both the extent of immunodeficiency and the duration of time spent with low CD4 levels is linked to an increased risk of both AIDS and non-AIDS events compared individuals with good CD4 recovery on treatment. These findings should spur renewed efforts to find immune-based therapies that might be able to boost immune reconstitution and thereby reduce risk of illness in this population, but there was little sign of that at CROI. The only significant IBT results that were presented described the sad denouement to the protracted tale of interleukin-2, which failed to show any clinical efficacy in two very large randomized trials, ESPRIT and SILCAAT. Those presentations and the other limited oral abstract offerings on immune-based therapies can be viewed in the webcast of the Tuesday morning session.
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