Modeling the HIV-1 Antiretroviral Therapeutic Drug Interaction.

To model the ART (antiretroviral therapeutic) drug interaction with the HIV-1 virus, a two-domain model is proposed that separates HIV-1 into a stable non-proliferating domain where the virus is integrated into the host resting memory CD4+ t cells; and, a second domain where the virus is in the blood in a rapidly reproductive state. ART inhibits blood HIV-1 reproduction levels sufficient to prevent progression to the AIDS end-stage, the principal goal of ART. There are 25 FDA approved antiretroviral drugs toward this goal grouped into 6 classes: NRTIs (nucleoside/nucleotide inhibitors), NNRTIs (non-nucleoside/nucleotide inhibitors), PIs (protease inhibitors), FIs (fusion inhibitors), CCR5s (chemokine cell receptor 5 antagonists), and INSTIs (integrase inhibitors).2 However as the memory CD4+ t cell host-integrated HIV-1 is in a stable state, it is unaffected by ART. Consequently, proliferation in the blood will continue, if unchecked by drugs.1 Against this dual function capability of HIV-1, no cure is possible; and, control levels of HIV-1 sufficient to prevent the AIDS end stage must be maintained. Adherence by patient to treatment regimen, thus, becomes crucial. In place of extant indirect measures of HIV-1 inhibition by ART (e.g., number of weeks to achieve control levels), rate of inhibition is proposed as a direct measure expressed by the differential equation formula: r =HIVJ -HIVk/HIVJ-HIVN where j and k refer to HIV-1cps/ml in the initial and subsequent observations; while, N refers to the total overall count of cps/ml. In a retrospective case history research study with 14 Syracuse VA HIV-1 outpatients, the rate measure was found to provide a quantitative basis for the HAART characterization, showing a stable high rate of inhibition, rs = .9 - 1.0 of the total available virus cps/ml with almost no variability among patients.