| Summary: | Primary HIV infection is characterized by high levels of plasma viremia and a transient decrease
in CD4+ T-lymphocytes count. The initial peak of viral load would subside on its own in a few
weeks due to the development of the host's specific anti-HIV immune response. A virologic
setpoint would then be established reflecting the balance between the basal level of viral
replication and the host's response to it. Studies have shown that the level of this setpoint is
predictive of long-term HIV disease outcome. By intervening with combination antiretroviral
therapy during primary HIV infection, it is our hope that the virologic setpoint would be lowered
even more resulting in a further delay of HIV disease progression. In this project, it was shown
that double therapy with nucleoside analogs in patients with primary HIV infection could only
induce transient viral suppression and partial immune reconstitution. The average reduction of
viral load in the cohort from baseline to the virologic setpoint was about 1.3 log (95% reduction)
in the presence of double therapy. CD4 cell counts were generally found to decline gradually
once the virologic setpoint was established. This therapy was found to lack the anti-viral
potency needed to treat patients with acute HIV infection most effectively. In contrast, the study
of triple drug therapy in the same setting has shown that suppression of viral replication in the
plasma (to less than 20 copies/mL) could be achieved in patients who had been through double
therapy or had withdrawn from treatment. This antiviral effect of triple drug therapy was
sustained (-100 weeks in one patient), with an associated increase in CD4 cell count. Therefore,
as in established HIV infection, triple drug therapy is highly suggestive to induce long-term
maximal viral suppression and immune reconstitution in patients with early (primary or postprimary)
HIV infection. This may have relevant long-term clinical benefit, slowing down
disease progression and prolonging the period of latency. === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate
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