title: Variable effect of co-infection on the HIV infectivity: within-host dynamics and epidemiological significance.
abstract: BACKGROUND
  Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals.
  
  
  METHODS
  We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface.
  
  
  RESULTS
  Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased.
  
  
  CONCLUSIONS
  Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.
authors.affiliation: Department of Biology, University of Kentucky, Lexington, KY, USA. dfc2002@qatar-med.cornell.edu
authors.forename: Diego F
authors.initials: DF
authors.lastname: Cuadros
authors.forename: Gisela
authors.initials: G
authors.lastname: García-Ramos
mesh_terms: D060085:Coinfection / Q000453:epidemiology / Q000821:virology*; D015658:HIV Infections / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D006801:Humans; D008288:Malaria / Q000821:virology; D011336:Probability; D019562:Viral Load; D014779:Virus Replication