title: Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains.
abstract: One of the serious threats facing the administration of antiretroviral therapy to human immunodeficiency virus (HIV-1) infected patients is the reported increasing prevalence of transmitted drug resistance. However, given that HIV-1 drug-resistant strains are often less fit than the wild-type strains, it is expected that drug-resistant strains that are present during the primary phase of the HIV-1 infection are replaced by the fitter wild-type strains. This replacement of HIV-1 resistant mutations involves the emergence of wild-type strains by a process of backward mutation. How quickly the replacement happens is dependent on the class of HIV-1 mutation group. We estimate the backward mutation rates and relative fitness of various mutational groups known to confer HIV-1 drug resistance. We do this by fitting a stochastic model to data for individuals who were originally infected by an HIV-1 strain carrying any one of the known drug resistance-conferring mutations and observed over a period of time to see whether the resistant strain is replaced. To do this, we seek a distribution, generated from simulations of the stochastic model, that best describes the observed (clinical data) replacement times of a given mutation. We found that Lamivudine/Emtricitabine-associated mutations have a distinctly higher, backward mutation rate and low relative fitness compared to the other classes (as has been reported before) while protease inhibitors-associated mutations have a slower backward mutation rate and high relative fitness. For the other mutation classes, we found more uncertainty in their estimates.
authors.affiliation: Department of Mathematics, Makerere University, P.O. Box 7062, Kampala, Uganda; Department of Computing and Technology, Uganda Christian University, P.O. Box 4, Mukono, Uganda. Electronic address: kitz@cns.mak.ac.ug.
authors.forename: J M
authors.initials: JM
authors.lastname: Kitayimbwa
authors.affiliation: Department of Mathematics, Makerere University, P.O. Box 7062, Kampala, Uganda. Electronic address: jytmugisha@cns.mak.ac.ug.
authors.forename: J Y T
authors.initials: JYT
authors.lastname: Mugisha
authors.affiliation: Facultad de Ciencias, Universidad de Colima, Bernal Díaz del Castillo 340, Colima, COL, C.P. 28045, Mexico. Electronic address: rsaenz@ucol.mx.
authors.forename: R A
authors.initials: RA
authors.lastname: Saenz
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate
chemical_list: D019380:Anti-HIV Agents
keywords: Backward mutation rate; HIV-1; Kaplan–Meier estimates; Virus mutations; Within-host model