Mathematical Analysis of the Probability of Spontaneous Mutations in HIV-1 Genome and Their Role in the Emergence of Resistance to Anti-Retroviral Therapy

摘要

High mutability of HIV is the driving force of antiretroviral drug resistance, which represents a medical care challenge. The proposed model represents a mathematical analysis of the mutability of each gene in the HIV-1 genome. It depends on a linear relation wherein the probability of spontaneous mutations emergence is directly proportional to the ratio of the gene length to the whole genome length. The mathematical analysis shows that tat , vpr and vpu are the least mutant genes in HIV-1 genome, and protease PROT gene is the least mutant gene component of polymerases POL . Accordingly, tat , vpr and vpu are the best candidates for HIV-1 recombinant subunit vaccines or as a part of “prime and boost” vaccine combinations. Also, the protease inhibitor-based regime represents a high genetic barrier for HIV to overcome.