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HIV's Confounding Superpowers

By Jackie Powder

As a founder of the Rakai Health Sciences Program in Uganda, Maria Wawer, MD, MHSc, has led some of the most influential HIV/AIDS research in the past two decades.  Still, the cunning of the HIV virus sometimes astonishes even her.

New research from Rakai upends conventional thinking about the virus’s powers of superinfection, a condition in which an HIV-infected person later acquires a second, new viral strain.

The first study of superinfection in a general population, published online June 5 in the Journal of Infectious Diseases, suggests that it is more common than initially thought and is not limited to groups at high risk for HIV, such as sex workers and intravenous drug users.

“The study shows that superinfection … is not rare, and the implications for vaccine and other prevention research may be quite substantial,” says Wawer, a senior author of the study and professor in Epidemiology. “This is one clever virus.”

Although the first cases of HIV superinfection were identified more than 10 years ago, there has been ongoing debate about how frequently it occurs.

Earlier superinfection studies focused primarily on high-risk populations—Kenyan sex workers, intravenous drug users in Thailand and men in the U.S. who have sex with men.

The big question for Andrew Redd, PhD, staff scientist at the National Institute of Allergy and Infectious Diseases and lead author of the new study: How common is superinfection in a broader heterosexual population?

For answers, he turned to the Rakai Program, which follows the health of a 14,000-member cohort and has a massive data repository of blood samples and interviews to better understand HIV transmission and prevention.

“The monitoring of this population for 18 years gave us the statistical power and samples to take a look at this question in a general population,” says Redd. “It’s an ideal place to compare rates of diseases because people aren’t selected on risk factors or certain characteristics. If you live in this village, you’re asked to join the study.”

Researchers tested HIV-positive blood specimens collected between 1998 and 2004 from 149 randomly selected members of the Rakai cohort. They looked at two samples: one taken at the time of initial HIV diagnosis and the second up to eight years later, but prior to when the patients began antiretro-viral (ARV) therapy.

Using a highly sensitive ultra-deep virus sequencing technology, scientists captured “snapshots” of the entire virus population and identified seven cases of superinfection. The observed superinfection rate in this study was 1.4 per 100 person years.

The finding raises important questions about the immune system response of the initial HIV virus and may have implications for future vaccine design, Redd says.

Says Wawer: “We need to do a lot more work with our immunology colleagues to try to understand why the initial infection does not protect persons from superinfection.”

From a clinical standpoint, based on existing research, a diagnosis of superinfection doesn’t appear to diminish the effectiveness of ARV therapy, the standard treatment for HIV. However, scientists have voiced other concerns, says Redd. It’s unclear whether superinfection leads to an accelerated progression of HIV to AIDS or whether superinfection increases the transmissibility of the virus. And the potential for superinfection with an ARV-resistant strain is another unknown.

In the meantime, Redd says that it makes sense for clinicians to discuss superinfection with patients newly diagnosed as HIV positive.

“You don’t have to be high risk to be at risk for superinfection,” he says.