Understanding drug resistance for monotherapy treatment of HIV infection (Q1364700)

A deterministic mathematical model is developed to investigate monotherapy treatment strategies of HIV patients in the presence of drug-resistant mutant HIV strains. The model is a nonlinear system of differential equations for the following five variables: the infected \(\text{CD}4^+\) \(T\) cells \(T(t)\), the wild-type virus and the mutant virus infected \(T\) cells \(T^s(t)\) and \(T^r(t)\), and the wild-type and the mutant viral load \(V_s(t)\) and \(V_r(t)\), respectively. Model features allow infection of \(T\) cells by both sensitive and resistant strains, release of newly produced virion, growth, mutation, clearance of virion, and \(T\) cell proliferation. Monotherapy is modeled for a variable time window by reduction of viral infectivity. This is implemented by multiplying the infection rate of \(T\) cells by free virus \(V_s\) and by multiplying with a treatment effectiveness parameter \(P_1\). A similar parameter \(P_2\) is applied to the external lymphoid system. A total of 27 model parameters -- 9 time dependent - are specified from clinical data. A numerical simulation study is performed to model the above described five variables for different treatment schedules on an individual basis. The results are compared qualitatively with clinical \(\text{CD4}^+T\) cell courses from 6 key AIDS studies performed between 1990 and 1995. Treatment benefit is based on increase or retention of \(\text{CD4}^+T\) cell counts and on low viral titer. Best monotherapy treatment effect is suggested by this model when the treatment starts in a middle region of \(250/\text{mm}^3\) to \(400/\text{mm}^3\) of \(\text{CD}4^+\) cell count and when a careful balance beteen mutant and wild-type HIV strains is achieved.