Photo by Todd McNaught
When it comes to HIV infection, lightning really can strike twice. According to a recent Human Biology Division study, having HIV and getting reinfected with a different strain of the virus — once thought a rare occurrence — may actually be quite common.
Bhavna Chohan and colleagues have found that reinfection may occur almost as often as first infections in women with continued exposure to HIV-1. In the first long-term study of the incidence and timing of HIV-1 reinfection in individuals infected through heterosexual contact — the population most typical of the global HIV pandemic — Chohan found the risk of reinfection was about half the predicted risk of initial infection. Additional cases of reinfection may have been missed because only 10 percent of the HIV-1 genome was studied in the samples.
The findings, which appear in the August issue of the Journal of Virology, have major implications for the development of an AIDS vaccine. The possibility of reinfection indicates that an immune response triggered by a vaccine to prevent infection by one strain of HIV may not protect against all other strains. A vaccine's effectiveness is likely to vary in different populations unless a method is developed that guards against many virus strains.
"It's critical to better understand the immune responses that are lacking in people who become reinfected so that improving these responses can be the focus of vaccine-development efforts," Chohan said.
Chohan, a graduate student in Dr. Julie Overbaugh's lab, found HIV reinfection occurred in three of 21 women who were followed for an average of three years after their first HIV-1 infection. Because this group of women had been monitored closely for many years, the authors could compare the risk of first infection to the risk of reinfection with HIV-1.
A parallel study by scientists at the University of California, San Diego, found similar HIV reinfection rates in high-risk men who have sex with men.
"In our previous studies, some of the molecular analyses showed HIV-1 sequences that look like hybrids or mosaics of different strains, so the question really was, 'Why were two strains present in the same patient?'" said co-author Dr. Julie Overbaugh, of their hypothesis that reinfection was occurring. For the subsample, the researchers followed women who were initially infected with a subtype of the virus less common in that area of Kenya and looked for evidence of reinfection with the most prevalent subtype.
Although HIV reinfection — often called superinfection — was first seen in a chimpanzee in 1987, the first such clear cases weren't reported in humans until 2002. Until that point, it was generally thought that individuals could not become infected with multiple, distinct HIV-1 strains.
The assumption has sometimes been that cases of reinfection are the result of exposure to different HIV strains more or less simultaneously, before the person's immune system has a chance to react. However, in Chohan's cases, the second virus strain emerged about a year after the first infection when viral levels were high, suggesting that well-established HIV-1 infection provided little benefit in immunizing against reinfection.
Reinfection poses additional treatment challenges, too. Now that antiretroviral treatment is starting to become available in Africa, there is concern that people may get treated with medications for a specific HIV strain and get superinfected with a strain that is not sensitive to treatment, said Chohan, referring to other documented cases. Such cases also showed the patients' disease progressed more rapidly than those infected with a single strain.
"Reinfection makes it much more complicated to treat a person because now you potentially have to treat the new resistant strain," Overbaugh said, adding that the "mixing" of different drug-resistant strains within individuals could render current medications less potent.
Overbaugh presented the study results at two international AIDS conferences. "We started presenting the data way before we published it because we thought it was so important," she said. "Some people didn't think it was important for vaccines, and others thought it was critical. The reality is that vaccines have been so challenging and difficult, it is a bit disheartening to think about one more problem to be considered. But I think there is a lot to learn from these cases that could lead to new vaccine concepts."
Chohan and Overbaugh, along with graduate student Anne Piantadosi, are now researching whether individuals can be reinfected with more closely related viral strains of the same subtype. "It's an important question, as this will tell us whether we can make vaccines that are more strain-specific," Overbaugh said. "If more related strains are less likely to reinfect a person than more distantly related viruses, then we may need to make 'regional' vaccines."
Overbaugh's lab is also trying to develop a rapid screening test to determine if reinfection has taken place. In addition, they hope to determine risk factors for reinfection, such as the presence of other sexually transmitted diseases. They will also examine if there is a window of time when HIV reinfection is more likely as this may provide clues as to which immune responses are critical for protecting against reinfection.
Stephanie Rainwater, a research technician in Overbaugh's lab, and Ludo Lavreys, a UW instructor and field director for the study, contributed to the National Institutes of Health-funded project.
Chohan's full-circle journey: From Africa to America and back again
A lab worker collecting study samples in a remote corner of the globe is unlikely to ever cross paths with the scientist receiving and working with those specimens in a faraway, developed country. But for Bhavna Chohan's research, the collector and receiver are one in the same.
Life has come full circle for Chohan, who headed a lab at the Coast Provincial General Hospital in Mombasa, Kenya, in the mid-1990s and spent her time screening high-risk groups for HIV/AIDS studies. Today, as a graduate research assistant in Dr. Julie Overbaugh's lab, she conducts research utilizing the archive blood samples she had played a role in collecting a decade ago.
"Whenever I pick up a sample, I see my own writing," she said. "In Mombasa, I saw all of the studies that were being published, and it was very exciting. I could see the implications and applicability of the research. I got very interested and decided I wanted to further my education." Chohan and Overbaugh first met in 1993 when Overbaugh went to Kenya to help set up a lab for her HIV/AIDS research. Chohan began work at the Hutchinson Center in 2001 while beginning doctoral studies at the University of Washington as part of the International AIDS Research and Training Program.
Today, Chohan's sister runs the lab in Mombasa. In another year, Chohan plans to move back to Kenya with her newly minted doctorate degree and establish a molecular virology lab and further collaborate with the Center and UW. "With this training, now I have the expertise to set up the lab," she said.
"Bhavna will set up a diagnostic-type clinical lab there to complement our research and molecular lab here," said Overbaugh.
From her former role on the front lines of the pandemic to her quest for knowledge and education today, Chohan's future work in Africa is likely to make a difference in the lives of more than 1 million Kenyans now living with HIV/AIDS.