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Combination antiretroviral therapy in primary and post-primary HIV infection

University of British Columbia

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in the plasma (to less than 20 copies/mL) could be achieved in patients who had been through double therapy or had withdrawn from treatment.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.

Thesis/Dissertation

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2009-06-29

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http://hdl.handle.net/2429/9821

Experimental Medicine

University of British Columbia

UBCV

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