Statisticians lend critical expertise to infectious disease research

CBAR researchers
CBAR researchers Michael Hughes, Scott Evans, and David Shapiro

April 27, 2017 — A positive HIV test result was once a near-certain death sentence, with more than 75% of people infected with the virus in the 1980s dying from AIDS. Today, HIV can be managed with antiretroviral medication, and a cure doesn’t seem quite so out of reach—thanks in part to a group of statisticians and epidemiologists at Harvard T.H. Chan School of Public Health.

These researchers, based at the Center for Biostatistics in AIDS Research (CBAR), are part of an international network of researchers—the AIDS Clinical Trials Group (ACTG)—whose work evaluating antiretroviral drugs and testing multi-drug regimens helped establish current treatment guidelines for HIV patients. Findings from the group’s studies have contributed significantly to the dramatic reductions in AIDS mortality in the U.S. and globally.

CBAR researchers have a hand in the design, monitoring, and interpretation of more than 50 clinical trials (testing treatments on human volunteers) and laboratory studies each year through ACTG. They also work on more than 150 additional studies through the three other major National Institutes of Health-funded research networks for which they serve as statistical center, and collaborate with colleagues at the Harvard T.H. Chan School of Public Health AIDS Initiative.

CBAR’s ongoing work on HIV includes studying the heightened risk of end-organ disease in the infected population as they age, and exploring new approaches for controlling HIV in infected patients with the ultimate goal of curing the disease. The group has also broadened its scope to include studies related to the prevention and treatment of tuberculosis, influenza, and antibiotic resistant bacterial infections.

Two decades of innovation

The Center was founded within the Department of Biostatistics in 1995 by the late Steve Lagakos, a faculty member and former department chair, expanding on a previous center established by a NIH grant in 1989. His efforts to bring innovative statistical techniques to infectious disease research are now being continued under the leadership of Michael Hughes, professor of biostatistics.

Teasing out the possible risks and benefits of a drug requires a high level of statistical expertise both in identifying optimal designs for studies and in addressing challenges such as extraneous factors that may distort data analysis, Hughes said. That’s where CBAR comes in. “These are statisticians who get the underlying basic science and clinical science behind infectious diseases research. They really understand the disease processes and how best to design and analyze research studies in that setting,” said Hughes.

Research by CBAR statisticians, led by Principal Research Scientist David Shapiro, and colleagues with the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, has shown that it is possible to virtually eliminate mother-to-child HIV transmission among women with access to treatment. Complementing this effort is work led in CBAR by Paige Williams, senior lecturer in biostatistics, in the Pediatric HIV/AIDS Cohort Study (PHACS) to find out whether the mothers’ use of antiretroviral drugs during pregnancy affects birth outcomes or has any long-term consequences for their children’s health and development.

Tackling antibacterial resistance and tuberculosis

CBAR researchers, led by Senior Research Scientist Scott Evans, are bringing new thinking to the evaluation of drugs to fight antibacterial resistance, including developing more effective strategies for designing and analyzing studies of antibiotics. They are also working on evaluations of new diagnostic tests that can quickly determine whether a patient is susceptible or resistant to a particular antibiotic.

Another relatively new research area for CBAR is tuberculosis (TB) research with statisticians involved in several clinical trials of treatments for adults, children, and pregnant women. Hughes is leading the statistical team involved in a large international trial testing a drug to prevent development of active TB in individuals living with people who have been diagnosed with multi-drug-resistant TB. This is an area identified by the World Health Organization as needing evidence to guide treatment recommendations.

New challenges in HIV treatment

The CBAR team is still working to understand the virus that it has been studying since the beginning—HIV. Efforts include understanding the long-term health consequences of HIV as the infected population ages. Compared to the general population, HIV-infected individuals are at higher risk for diseases associated with the aging process, including cardiovascular disease (CVD), osteoporosis, and neurocognitive dysfunction.

In collaboration with researchers at Massachusetts General Hospital, Principal Research Scientist Heather Ribaudo is leading work at CBAR on a major international trial to test the efficacy of statins to reduce the risk of CVD in HIV-infected people. What is novel about this trial, Hughes said, is that it is targeting people with a range of cholesterol levels. Those who are on the low side would not typically be treated with statins, but the researchers believe that the drugs may also help reduce chronic inflammation, a risk factor for CVD that is common in HIV patients.

Although the consequences of an HIV diagnosis have changed since those first terrifying and uncertain years, Hughes said that there is no less of a sense of urgency for the researchers. “Every success brings a new challenge, and we’re now engaged in research on what was perhaps unthinkable early in epidemic: the possibility of curing HIV,” he said.

Amy Roeder

photo: Sarah Sholes