Breakthrough Behind the Scenes

Courtesy of Kimberly Powers

Antiretroviral drugs that can slow or stop the progression of HIV infection while limiting HIV transmission could be a game changer in the worldwide HIV epidemic. That's why Science recognized the idea of "treatment as prevention" as its scientific breakthrough of the year, crediting the lab of infectious diseases researcher Myron Cohen, a physician-scientist at the University of North Carolina School (UNC) of Medicine in Chapel Hill, with discovering and investigating one of the most promising antiretroviral drugs, HPTN 052.

In a recent paper in The New England Journal of Medicine, Cohen and colleagues argue that HPTN 052 is effective in preventing transmission between sexual partners. But, Cohen says, scaling up the intervention to impact populations requires a more thorough understanding of how HIV spreads.

"Kim walked into my office all those many years ago, and here was this very smart woman from Los Alamos, very well educated, and it was like, whoa, she can do things we normally wouldn't be able to do so long as we train her properly." -- Myron Cohen

Read more about HIV treatment as prevention, as well as other important breakthroughs from the past year, in this week's issue of Science.

Enter Kimberly Powers, who started her Ph.D. in epidemiology at UNC in 2003 and joined Cohen's lab a year later, contributing epidemiology research and mathematical models that have helped scale up the HPTN studies. Now a postdoc in the Cohen lab, she's trying to clear one of treatment-as-prevention's major hurdles: understanding how HIV is transmitted during its so-called acute stage, which occurs before the infection is recognized. Her most recent findings suggest that targeting those early infections with drugs like HPTN 052 could deliver a serious blow to the HIV epidemic.

A quantitative background

Powers started off as a math major and physics minor at Hamilton College in Clinton, New York, but she knew then that she wanted to help people. "I had tentative aspirations of becoming a physician, but I wasn't sure. I wanted to try my hand at a few different things before really settling on a career path," she says.

The first thing she tried after college was a job at a health care consulting company, where she first encountered public health and epidemiology issues. Next, she spent a year researching tobacco use prevention and control at the University of New Mexico, Albuquerque, where it occurred to her that she could use her mathematics background to help people. "It started to become quite evident to me that a research career in infectious disease epidemiology and mathematical modeling would be a fairly perfect combination of my longstanding interests in math and biology and medicine, as well as my emerging interest in infectious disease transmission and public health more generally," she says.

Kimberly Powers

Courtesy of Kimberly Powers

Her chance to combine those interests came during her next job, at Los Alamos National Laboratory. There, she studied mathematical models that could explain the behavior of viruses within a host and helped scientists develop new models. Then she applied to and was accepted at UNC.

Powers started at UNC and, during her second year, heard Cohen give a talk about using antiretroviral drugs as a population-level preventative measure against HIV transmission. "I'd always been intrigued by the type of work he was doing and I basically cold called him and asked if I could work with him, and the rest is history," she says.

From Cohen's perspective, Kim's appearance wasn't history, it was the future. "Kim walked into my office all those many years ago, and here was this very smart woman from Los Alamos, very well educated, and it was like, whoa, she can do things we normally wouldn't be able to do so long as we train her properly," he says.

Cohen welcomed her into his lab, his expectations high. Together, they developed her dissertation plan. Powers would study how large of a role acute- and early-stage HIV infection plays in transmission within a population in Lilongwe, Malawi.

But first she would need a proper education in epidemiology. Cohen asked his colleagues at the London School of Hygiene and Tropical Medicine and Imperial College London if they would accept her as a student for a year. They did, so she spent the next year with "world-class epidemic modelers," learning how to account for variables such as drug efficacy and behavior and how to build models that could accurately capture the dynamics of viral transmission. She stayed on for a second year, continuing to learn and serving as a teaching assistant.

Once back in North Carolina, she began to take frequent trips to an STD clinic in Lilongwe. She spent weeks at a time at the clinic, helping to improve patient care, tracking trends in HIV and other STD patterns, and observing the behaviors of infected and uninfected people. She developed a new database against which to test models of HIV transmission.

Beyond plausibility

Between visits to Lilongwe, she and Cohen analyzed the data. Over the course of 7 years of graduate work, Powers published 10 papers on the treatment as prevention of acute STD infection. Cohen incorporated her findings into his own work on HPTN 052. "The kinds of things she pursued were in sort of a parallel universe to 052," he says. "For 052, we spent about 10 years working on the biological plausibility. … We were interested in [the question], 'Was it really feasible to treat yourself out of the epidemic?' And we were doing all kinds of studies with antiviral drugs and pharmacology, and all of it led us to believe the idea was plausible."

To move from "plausible" to convincing policymakers, Cohen says, they had to address one big unanswered question: How much infection goes on before people begin treatment?

Powers finished her Ph.D. in 2010, became a postdoc in Cohen's lab, and set out to seek a definitive answer. Poring over data from Lilongwe, she mapped out who infected whom and at what point in the course of their infection. She found that approximately 38% of the transmission occurred before infected people or their physicians knew about it. "We always felt that it was an important factor driving transmission," she says, but when the number turned out to be that high, "We were really quite surprised." Powers, Cohen, and colleagues, published their results in The Lancet.

Is HPTN 052 efficacious for population-level prevention? Powers and Cohen think it might be -- but only if they can find a way to detect the virus in its early stages. "Without Kim, we never would have known that. … It was her God-given skills that allowed us to do this work," Cohen says.

How will they detect the virus early? They don't yet know. It could be through more advanced blood screening, or perhaps through symptom and behavior detection. Powers is working on that problem now. If that problem can be solved, antiretroviral drugs like HPTN 052 could help stop the HIV epidemic in sub-Saharan Africa, if not more broadly, they say.

Powers is also beginning to look at HIV transmission in other populations. She's starting a new study looking at HIV in U.S. prisons. "The proportion of Americans with HIV who cycle through the criminal justice system is really quite huge," she says. "The thinking is that improving testing and treatment in that population could have important secondary benefits on transmission."

Eventually, she'd like to strike out on her own and become an independent investigator, continuing to study HIV transmission while helping mathematical modelers and epidemiologists cooperate better. "I'm interested in bridging gaps between traditional epidemiology and mathematical modeling, hopefully developing improved methods for studying infectious diseases," she says.

Before she can take those big leaps, though, she has a few smaller steps to take. "One thing I haven't done at all yet is write my own grant," she says. "So that's kind of the next big thing for me."

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