Some HIV subtypes may progress faster than others, according to a new study by UW researchers.

The study tracked more than 3,000 women over 14 years in Mombasa, Kenya. Those infected with HIV subtype D were twice as likely to die from their disease as women infected with subtype A. Subtype is a way of grouping viruses with similar genetic sequences, with HIV having a range of A-K subtypes.

This difference between these A and D subtypes remained even when the viral load, or amount of virus circulating in the bloodstream was the same, said Julie Overbaugh, an associate professor of microbiology and author on the study.

“The current number of women who require therapy has reached 120. Of that number, about 20 percent is made up of subtype D,” said Scott McClelland, field director of the study.

Of all the women in the study, 78 percent are infected with subtype A and 14 percent are infected with subtype D, according to the report.

No one is sure exactly why one subtype may progress to mortality faster than another, Overbaugh said.

“We know from older studies, where we looked at the simian immunodeficiency virus (SIV), that changes in glycosylation, or the sugars on the outside of the virus, can affect progression,” she said.

SIV is a virus similar to HIV found in monkeys. The sugars that disguise this virus make it harder for the body’s antibodies to recognize virus particles, she said.

“That’s one mechanism, but there are certainly others, and we don’t know what they are,” Overbaugh said.

Bhavna Chohan, a molecular virology doctoral student and one of the lead authors on the paper, said the difference may be caused by the way different HIV subtypes enter immune cells. Past research has shown that another subtype (subtype B) uses the CCR5 receptor on immune cells to enter immune cells early in the infection process, but then switches to using another receptor (CXCR4) later on in the infection, once a person’s disease progresses, she said.

A recently published study in Uganda showed that some of subtype D uses the CXCR4 receptor for entering the immune cell.

“Therefore, we hypothesize that subtype D viruses may be using CXCR4 for cell entry, as subjects infected with subtype D progress to disease rapidly,” Chohan said. “We don’t have data to show that they do [use CXCR4] early in infection, and our lab is currently investigating that possibility.”

These results may lead to different treatment regimes depending on subtype, said Jared Baeten, one of the lead authors and a fellow in allergy and infectious diseases.

“That would be a great thing, if we could figure out if you have a relatively benign version of HIV just from genetic sequencing of type,” Overbaugh said.

People with more aggressive subtypes might get earlier treatment.

“If we can subtype people and start treatment sooner, that might prolong their life,” Chohan said.

Using subtype to tailor treatment has not been shown to be useful yet, and more research is needed to untangle the relationship between subtype, disease progression, and treatment response.

Subtype-tailored treatment would not be as useful in the United States, where almost all HIV cases are subtype B, Baeten said.

“Clearly it’s very challenging to do widespread sequencing and not at all clinically indicated,” Baeten said. “If it’s shown routinely that there is a change of outcome when you start treatment sooner, then maybe it would become useful. But you’d have to wait for easier methods of subtyping. Right now that should not be Kenya’s priority.”

Reach reporter Tia Ghose at news@thedaily.washington.edu.

As of 2003, approximately 7 percent of the Kenyan population was estimated to be HIV positive. Of those, two-thirds are estimated to be women.

In Kenya:

Percentage of young men aged 15 - 24 who had sex with a casual partner in the past 12 months: 84 percent

Percentage of young women aged 15 - 24 who had sex with a casual partner in the past 12 months: 30 percent

In the United States:

As of 2003, approximately .6 percent of the U.S. population was HIV positive. Of those, about 73 percent are estimated to be men.

- UNaids.org

More than 90 percent of the women in the cohort were bar workers. They used sex work to supplement their income, but did not use sex work as their primary form of income.

Women in the study receive HIV screening, counseling about STD risk, free condoms, STD treatment and standard of care (antiretroviral therapy) if they test positive for HIV.

- Chohan and McLelland