HSV for tumour lysis

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This house believes that virus shedding is a surrogate marker for genital herpes transmission: The case for

Presented by P Griffiths
Royal Free and University College Medical School, London, UK.

Measurements of viral load have become clinically important over the past decade. I will cite an example where viral load measurements of a herpesvirus have informed our understanding of the pathogenesis of disease within the individual. In 1975, investigators in Birmingham, Alabama showed that neonates with congenital cytomegalovirus (CMV) disease had a significantly higher viral load than those without disease. We confirmed these results in the modern era using polymerase chain reaction (PCR) in renal transplant patients, and demonstrated that the plot of probability of disease against virus load is not linear but sigmoidal; a concept we call the ‘threshold concept’ of CMV disease. The implication of these findings is that a relatively small reduction in viral load may translate into a disproportionately positive clinical outcome.

When applied to the transmission of virus from person to person following needlestick injury, the risk of transmitting hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV is related linearly to the viral load found in the donor blood. In contrast, there is evidence from perinatal HCV and heterosexual HIV that transmission of virus may follow a threshold-shaped sigmoidal curve. While additional factors can influence transmission, such as the age of the individual and the number of sexual acts that are performed in the case of HIV, it is clear that measurements of viral load have a major contribution to make in understanding transmission of HIV.

Turning to genital herpes, it is clear that transmission often occurs in individuals who are asymptomatic and that transmission can be decreased by treatment. Shedding from the genital tract is common when detected by culture and even more common when detected by PCR. Shedding also decreases with aciclovir, famciclovir or valaciclovir treatment, as shown in a series of randomised, controlled clinical trials. Thus we have to ask whether the reduction of both shedding and transmission of genital herpes through antiviral treatment are directly linked, i.e. is reduced shedding the mechanism by which valaciclovir reduces transmission?

In deciding how to vote in this debate, I suggest that the audience draws upon its medical knowledge and experience of infectious diseases in general, together with the specific data generated from a large number of natural history studies of genital herpes, to determine if it is plausible that HSV shedding from the genital tract could explain the treatment benefit observed. If you believe this is the case then you should vote for the proposition.

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Last Updated : 08/04/2004 15:14:12