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.