title: Exploring the impact of target cell heterogeneity on HIV loads in a within-host model.
abstract: HIV can be transmitted from blood plasma or semen of an infected male. Viral loads in blood plasma are routinely measured, but the same is not true of semen. Even before drug treatment, viral loads have been shown to be different in the two body compartments (blood and genital tract), and this heterogeneity may be exacerbated by treatments using those antiretroviral drugs which have different efficacies in the two compartments. In addition to this heterogeneity, and despite highly effective drugs (in the blood) low-level viral replication is commonly reported for HIV patients as are differences in drug resistant mutation patterns in the two compartments. In this paper we investigate the effect of target cell heterogeneity between compartments on HIV viral loads using a within-host model that includes wildtype and drug resistant strains of HIV. We find that modelling target cell heterogeneity in the blood and male genital tract gives different viral loads in the two compartments prior to treatment and allows low-level viral loads to persist during therapy even if drug penetration is good. The model also allows coexistence of the two viral strains (in the absence of a mutation mechanism) with different dominance patterns in each body compartment. Our results suggest that monitoring of blood plasma viral strains may not give an accurate picture of the strains of HIV being transmitted between individuals and that continued research into the nature of HIV target cells in the male genital tract would be beneficial.
authors.affiliation: Centre for Mathematical Biology, University of Bath, Claverton Down, Bath, UK. Z.D.Ward@bath.ac.uk
authors.forename: Zoë D
authors.initials: ZD
authors.lastname: Ward
authors.forename: K A Jane
authors.initials: KA
authors.lastname: White
authors.forename: George A K
authors.initials: GA
authors.lastname: van Voorn
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000592:standards; D024882:Drug Resistance, Viral; D005837:Genitalia, Male / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000635:transmission; D006801:Humans; D008297:Male; D008954:Models, Biological; D012661:Semen / Q000821:virology; D019562:Viral Load / Q000187:drug effects*
chemical_list: D044966:Anti-Retroviral Agents