Increased risky behavior always will cause infection and death rates to rise but, contrary to what some in the field have predicted, the new model projects a consistently better future if advanced anti-retroviral therapy is extended to more HIV-infected gay men.
"It's a complex interaction, but a simple outcome, really," says Sally Blower, PhD, associate professor of medicine, microbiology and immunology at UC San Francisco and lead author of a report on the study. "The more you treat, the better you will do, even if risk behavior and drug resistance go way up."
In the model's worst-case projection -- with risk behavior doubling and drug resistance severely diluting the therapy's effectiveness -- infection rates and deaths would still be lower after ten years than if treatment were not expanded.
The report, by a team of UCSF virologists and mathematical biologists, is published in the January 28 issue of the journal Science.
About half of the HIV-infected men in San Francisco are taking a combination of anti-retroviral drugs, in a treatment regime known as Anti Retroviral Therapy (ART) or Highly Active Anti Retroviral Therapy (HAART), the authors note. Since treated men are likely to retain some degree of infectivity, some AIDS experts have warned that expanding ART treatment could lead to an increased infection rate. In addition, drug-resistant HIV strains have already emerged and risky sexual behavior has begun to increase in San Francisco. These trends have led some to conclude that expanding use of the advanced ART or HAART therapy - particularly to those less prone to practice safe sex or to follow the difficult drug regimen carefully - would lead to increases in drug resistance, higher HIV infection rates and soaring AIDS deaths.
The new model shows otherwise. "Our model found that over ten years, expanding ART treatment in San Francisco will reduce HIV incidence rates and AIDS death rates below what they would be without expanded treatment," Blower stresses.
Although the model finds a beneficial effect of expanded drug treatment, it starkly reveals that increased risk behavior always leads to more infections and more AIDS deaths.
"Our predictions clearly show that expanding use of viral suppressing drugs to more gay men will always reduce HIV incidence and save lives compared to not expanding treatment, no matter what the rate of drug resistance or risk behavior is," Blower says. "But even small changes in risk behavior will reduce the benefits in the short run. Doubling of risky sexual behavior will negate benefits in the short run and limit them in the long term."
"Our results indicate it is imperative that bath houses not be re-opened and that people practice protected sex, particularly those who are on treatment," she added.
Co-author on the paper is Robert Grant, MD, assistant professor of medicine at UCSF and an AIDS specialist at the Gladstone Institute of Virology and Immunology. Hayley Gershengorn, a former research assistant in Blower's lab and now a Harvard medical student, is also a co-author.
Blower and colleagues developed the model to help AIDS experts assess drug treatment strategies given the high degree of uncertainty in future rates of drug resistance and risky sexual behavior as well as the effectiveness of treatment on both rates of infectivity and long-term survival. It is the first such model to project long-term drug effectiveness while incorporating so many types of uncertainty.
"We used the model to predict the unpredictable," Blower says. The model includes the potential effects of ART on the transmission dynamics of both drug-sensitive and drug-resistant HIV strains. It examines both a "best-case condition" (10 percent annual rate of emergence of resistance; no increase in risky behavior) and a "worst-case condition" (up to 60 percent of cases become drug resistant per year; risky sexual behavior doubles).
Reflecting the range of possible outcomes provided by the model, the Science paper is titled "A Tale of Two Futures: HIV and Anti-Retroviral Therapy in San Francisco."
The model identifies which factors affect how well anti-retroviral therapy works, and uses these factors to suggest how to ensure that the outcome is "the best of times," rather than "the worst of times," Blower points out. The key factor is the rate of risky sexual behavior.
Blower, Gershengorn and Grant have applied what is currently known about HIV biology and infectivity to knowledge of viral transmission and survival generally to develop the new mathematical model.
"We must move the study of epidemics beyond description to make it a predictive science," says Blower. "This is the only certain way to improve strategies to fight infectious diseases."
Grant cautions that although the researchers have used all available information, at this point there are only three years of data on the use of ART and the possibility of viruses becoming resistant to it.
In addition, he says, "the model indicates that relative virulence and transmissibility of HIV are critical determinants in predicting the epidemic behavior of a drug-resistant virus. More information on these two factors will be crucial in the coming years."
The research is funded by the National Institute of Allergies and Infectious Diseases, part of the National Institutes of Health.
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