In this article, we present a novel approach under the Fibonacci wavelet and collocation technique which is computationally efficient to obtain the solution of the model of CD4 + T cells of HIV infection. A system of nonlinear ordinary differential equations represents this mathematical model. We have approximated unknown functions and their derivatives using the operational matrix of integration of Fibonacci wavelets to transform this model into a set of algebraic equations and then simplified using a suitable method. It is anticipated that the proposed approach would be more efficient and suitable for solving a variety of nonlinear ordinary and partial differential equations representing the model of medical, radiation, and surgical oncology, and drug targeting systems that occur in medical science and engineering. Tables and graphs are included to show how the suggested wavelet method provides enhanced accuracy for a wide range of problems. Relative data and computations are performed over MATLAB software.