New Model Makes It Possible To Predict Emergence Of Antiviral Drug Resistance

June 01, 1998

Researchers led by a UC San Francisco scientist have developed a model for predicting the emergence of antiviral drug resistance and for identifying the key factors that generate drug resistance.

The model, reported in the June 1 issue of Nature Medicine and lauded in an accompanying review by a Yale School of Management professor of management sciences and medicine, looked specifically at the likelihood of drug resistance occurring with increased use of a drug to treat genital herpes. The findings predicted that while increased use would lead to elevated levels of drug resistant strains, the number of cases of the disease would significantly decrease.

However, the greater significance of the study, said the principal investigator, Sally Blower, PhD, an associate professor of microbiology, immunology and medicine at UCSF, is the potential use of the new methodology for predicting drug resistance in many infectious diseases prone to antibiotic or antiviral resistance, including HIV.

"The methodology we've developed and applied to genital herpes can be used as a health policy tool to predict the likelihood of future levels of antibiotic or antiviral resistance for numerous infectious diseases, including HIV," said Blower.

A tool to predict future drug resistance is sorely needed, according to Edward H. Kaplan, PhD, of Yale in his review of the study. "This new model," he said, "provides a way to challenge the inertia often seen in public health decisions in which the overwhelming cost and timing required by empirical studies renders such analyses unfeasible, leading by default to decisions not to promote drug treatment when there is a risk of drug resistance developing."

The UCSF mathematical model, which traced the dynamics of drug-sensitive and drug-resistant herpes simplex virus in the general population, was designed to predict how much drug resistance could be expected to emerge over the next 50 years if treatment rates increased, and to identify the key factors that would determine the emergence of drug resistance.

Using two forms of statistical analyses, known as uncertainty and sensitivity analyses, the researchers examined a wide range of numerical values considered plausible for every parameter in the model, ranging from the best, most likely, to worst case values. These numbers were approved by a panel of infectious disease experts.

"The results of the uncertainty and sensitivity analyses demonstrated," said Blower, "that increasing treatment rates would be extremely beneficial if there is a low probability that acquired drug-resistance will develop and/or if the drug-resistant strains that emerge are of low transmissibility. Currently many infectious disease experts believe that these conditions appear plausible but the precise values of these two parameters must be determined by future empirical studies."

Genital herpes is only treated in 10 percent of cases in the United States and often goes untreated altogether in Third World countries. The apparent reason, at least in the United States, is that most people who contract the condition don't find it bothersome enough to warrant the effort.

However, "the overwhelming finding of the study was that treating herpes epidemics would always be beneficial, in terms of the number of cases prevented in relation to the number of drug resistant cases that developed," said Blower.

The study found that, even in the worst case, at least five drug-sensitive infections could be prevented on average for each case of drug-resistant genetic herpes.

And since genital herpes is a risk factor for developing HIV, increasing treatment rates of genital herpes could potentially also have an important indirect and rapid effect on decreasing the incidence of HIV, she said. The study also found, however, that increasing treatment over a 50-year period correlated with a significant increase in drug resistant strains of the virus, which can be spread through sexual transmission or evolve naturally during treatment. In fact, after 50 years of increased treatment with the drug acyclovir, drug resistant strains accounted for 29 percent of infectious cases. Importantly, the model also identified the most influential factors in the emergence of strains of genital herpes resistant to drugs, which could lead to preventive measures, said Blower. They included the average number of infectious episodes per year, the transmission probability of drug-resistant strains and the average number of new sex partners.

The next step, however, she said, must be biological studies to determine the transmissibility of drug resistant strains and the likelihood of acquiring permanent drug resistance during episodic treatment.

As far as evaluating drug resistance in other infectious diseases, says Blower, "we suggest that the novel health policy analyses that we have presented and applied to genital herpes should now be applied to other infectious diseases."

The co-authors of the study were Travis Porco, formally a postdoctoral fellow in Blower's research group at UCSF and now a research scientist in the AIDS office at the San Francisco Department of Public Health, and Graham Darby, PhD, the international director for viral diseases research at Glaxo Wellcome Research & Development, which markets the drug acyclovir, used to treat genital herpes.

University of California - San Francisco

Related Public Health Articles from Brightsurf:

COVID-19 and the decolonization of Indigenous public health
Indigenous self-determination, leadership and knowledge have helped protect Indigenous communities in Canada during the coronavirus disease 2019 (COVID-19) pandemic, and these principles should be incorporated into public health in future, argue the authors of a commentary in CMAJ (Canadian Medical Association Journal)

Public health consequences of policing homelessness
In a new study examining homelessness, researchers find that policy such a lifestyle has massive public health implications, making sleeping on the street even MORE unhealthy.

Electronic health information exchange improves public health disease reporting
Disease tracking is an important area of focus for health departments in the midst of the COVID-19 pandemic.

Pandemic likely to cause long-term health problems, Yale School of Public Health finds
The coronavirus pandemic's life-altering effects are likely to result in lasting physical and mental health consequences for many people--particularly those from vulnerable populations--a new study led by the Yale School of Public Health finds.

The Lancet Public Health: US modelling study estimates impact of school closures for COVID-19 on US health-care workforce and associated mortality
US policymakers considering physical distancing measures to slow the spread of COVID-19 face a difficult trade-off between closing schools to reduce transmission and new cases, and potential health-care worker absenteeism due to additional childcare needs that could ultimately increase mortality from COVID-19, according to new modelling research published in The Lancet Public Health journal.

The Lancet Public Health: Access to identification documents reflecting gender identity may improve trans mental health
Results from a survey of over 20,000 American trans adults suggest that having access to identification documents which reflect their identified gender helps to improve their mental health and may reduce suicidal thoughts, according to a study published in The Lancet Public Health journal.

The Lancet Public Health: Study estimates mental health impact of welfare reform, Universal Credit, in Great Britain
The 2013 Universal Credit welfare reform appears to have led to an increase in the prevalence of psychological distress among unemployed recipients, according to a nationally representative study following more than 52,000 working-age individuals from England, Wales, and Scotland over nine years between 2009-2018, published as part of an issue of The Lancet Public Health journal on income and health.

BU researchers: Pornography is not a 'public health crisis'
Researchers from the Boston University School of Public Health (BUSPH) have written an editorial in the American Journal of Public Health special February issue arguing against the claim that pornography is a public health crisis, and explaining why such a claim actually endangers the health of the public.

The Lancet Public Health: Ageism linked to poorer health in older people in England
Ageism may be linked with poorer health in older people in England, according to an observational study of over 7,500 people aged over 50 published in The Lancet Public Health journal.

Study: Public transportation use linked to better public health
Promoting robust public transportation systems may come with a bonus for public health -- lower obesity rates.

Read More: Public Health News and Public Health Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to