Treatment of Respiratory Viral Coinfections

Abstract

With the advent of rapid multiplex PCR, physicians have been able to test for multiple viral pathogens when a patient presents with influenza-like illness. This has led to the discovery that many respiratory infections are caused by more than one virus. Antiviral treatment of viral coinfections can be complex because treatment of one virus will affect the time course of the other virus. Since effective antivirals are only available for some respiratory viruses, careful consideration needs to be given on the effect treating one virus will have on the dynamics of the other virus, which might not have available antiviral treatment. In this study, we use mathematical models of viral coinfections to assess the effect of antiviral treatment on coinfections. We examine the effect of the mechanism of action, relative growth rates of the viruses, and the assumptions underlying the interaction of the viruses. We find that high antiviral efficacy is needed to suppress both infections. If high doses of both antivirals are not achieved, then we run the risk of lengthening the duration of coinfection or even of allowing a suppressed virus to replicate to higher viral titers.

Keywords: antiviral; coinfection; drug efficacy; mathematical modeling.

Figure 1

Viral titer time courses for coinfections involving IAV/RSV (left) and hRV/PIV (right). Infections begin simultaneously with equal amounts of virus. The horizontal dashed line indicates the threshold used for determining infection durations.

Figure 2

Coinfection durations and outcomes for treated influenza and RSV coinfections. (Left column): Figures show the coinfection duration relative to an untreated coinfection where a value of 1 indicates that treatment has not changed the coinfection duration. (Right column): Figures show regions of different treatment outcomes: Dark blue indicates that both infections are detectable; light blue indicates that only IAV is detectable; yellow indicates that only RSV is detectable; and red indicates that both infections are suppressed. Figures show treatment with both antivirals reducing the infection rate (top row); the influenza antiviral reducing infection rate and the RSV antiviral reducing viral production (second row); the influenza antiviral reducing viral production and the RSV antiviral reducing infection rate (third row); and both antivirals reducing viral production (bottom row).

Figure 3

Coinfection durations and outcomes for treated rhinovirus and PIV coinfections. (Left column): Figures show the coinfection duration relative to an untreated coinfection where a value of 1 indicates that treatment has not changed the coinfection duration. (Right column): Figures show regions of different treatment outcomes: Dark blue indicates that both infections are detectable; light blue indicates that only hRV is detectable; yellow indicates that only PIV is detectable; and red indicates that both infections are suppressed. Figures show treatment with both antivirals reducing infection rate (top row); the rhinovirus antiviral reducing infection rate, and the PIV antiviral reducing viral production (second row); the rhinovirus antiviral reducing viral production and the PIV antiviral reducing infection rate (third row); and both antivirals reducing viral production (bottom row).

Figure 4

Viral titer time courses for coinfections with superinfection involving IAV/RSV (left) and hRV/PIV (right). Infections are started simultaneously with equal amounts of virus. The horizontal dashed line indicates the threshold used for determining infection durations.

Figure 5

Coinfection durations and outcomes for treated influenza and RSV coinfections. (Left column): Figures show the coinfection duration relative to an untreated coinfection where a value of 1 indicates that treatment has not changed the coinfection duration. (Right column): Figures show regions of different treatment outcomes: Dark blue indicates that both infections are detectable; light blue indicates that only IAV is detectable; yellow indicates that only RSV is detectable; and red indicates that both infections are suppressed. Figures show treatment with both antivirals reducing infection rate (top row); the influenza antiviral reducing infection rate, and the RSV antiviral reducing viral production (second row); the influenza antiviral reducing viral production and the RSV antiviral reducing infection rate (third row); and both antivirals reducing viral production (bottom row).

Figure 6

Coinfection durations and outcomes for treated rhinovirus and PIV coinfections. (Left column): Figures show the coinfection duration relative to an untreated coinfection where a value of 1 indicates that treatment has not changed the coinfection duration. (Right column): Figures show regions of different treatment outcomes: Dark blue indicates that both infections are detectable; light blue indicates that only hRV is detectable; yellow indicates that only PIV is detectable; and red indicates that both infections are suppressed. Figures show treatment with both antivirals reducing infection rate (top row); the rhinovirus antiviral reducing infection rate and the PIV antiviral reducing viral production (second row); the rhinovirus antiviral reducing viral production and the PIV antiviral reducing infection rate (third row); and both antivirals reducing viral production (bottom row).