• Development of virus-specific immune responses in SHIVKU-infected macaques treated with PMPA (MoOrA101)
  Authored by A. Kumar, N. Bischofberger, J. Lifson, O. Narayan

• Initiating a four-week-long oral HAART four hours after intravenous exposure of macaques with SHIV89.6P preserves from acute CD4+ cell decline (MoOrA102)
  Authored by B. Vaslin, O. Neildez, J. Larghero, H. Thiebot, K. Benlhassan, N. Dereuddre-Bosquet, P. Clayette, D. Dormont, R. Le Grand

There were two important presentations in the animal model section (MoOrA101 and 102). The authors of these studies tested the idea of the use of transient HAART during the acute infection period and the long-term impact of that intervention on viral load and prognosis of the disease. In Dr. Kumar's presentation (MoOrA101) four macaques were infected with SHIVKU. One week post-inoculation, two of the four animals were treated with tenofovir for 83 days. The two other macaques served as controls and received no treatment. The placebo macaques died within six months of AIDS. The animals which had received PMPA had a antiretroviral response during therapy, and after stopping it, the virus began to replicate quickly, but then the immune system of both animals controlled the productive replication of virus, and the animals remained free of diseases for more than one year. This was associated with virus-specific neutralizing antibodies, T helper cells, and CTLs.

Dr. Vaslin's presentation (MoOrA102) showed similar effects. Twelve cynomolgus macaques received AZT/3TC/IDV immediately after an intravenous infection, and then experienced lower viral loads and less CD4 declines after therapy was stopped.

I think these papers have profound implications in our approach of acute seroconversion. Current guidelines suggest the use of combination therapy, without a clear determination of the length of time, but with the implicit assumption is that is going to be for life. Perhaps these guidelines are wrong. Perhaps the right thing to do is to treat patients with acute seroconversion for a certain period of time and then stop therapy, let the immune system set a "set-point" lower than what it would have been without the intervention and restart the treatment when clinically indicated. If this is the case, networks would have to be established to identify patients with acute seroconversion and therapy would have to be administered for a short period of time, which obviously would be much cheaper than treatment for life. Obviously, this approach could even be used in the developing world.

This idea will obviously have to be tested in the setting of a clinical trial, comparing this approach to placebo, or continuous therapy as the current guidelines suggest.