HIV Dynamics and Integrase Inhibitors

The integrase inhibitor (INI) raltegravir has shown promising results in clinical trials to date, reducing second phase HIV RNA levels by 70% in comparison with standard regimens. These trial results have been limited by the 50 copies/ml detection limit of the HIV RNA assay and have not investigated the effect of an INI regimen on levels of latently infected cells. Mathematical models that duplicated previous raltegravir results were extended to estimate effects of an INI regimen on HIV RNA beyond second phase and on HIV DNA levels. Depending on assumptions underlying later phase HIV RNA generation and its interaction with latently infected cells, HIV RNA in later phases can be lower or show no difference with an INI, and similarly for HIV DNA. If latent infection is maintained by differentiation of stem cells with integrated HIV DNA, then an INI regimen will eventually have no added benefit. Other hypotheses that allow ongoing replication predict continually lower HIV RNA levels with an INI regimen, but this differential effect need not translate to a reduction in latent infection. Investigation of HIV RNA and HIV DNA levels with an INI will provide better understanding of how these components are generated and maintained under antiretroviral therapy.