HIV subtype predicts likelihood of early death from AIDS

Johns Hopkins scientists say an infected person's HIV subtype is a better predictor than viral load for determining rapid death from AIDS. Traditional testing standards help monitor the progression of an HIV infection to AIDS by keeping track of viral load, using a scale in which less than 50 viral particles per cubic milliliter of blood is considered suppressed disease and a viral load of more than 75,000 particles per cubic milliliter of blood means that the disease will progress more rapidly.

In what is believed to be the first analysis of viral subtype as a predictor of death from AIDS, which also takes into account viral load, the Hopkins team found that having viral subtype D made a person with HIV likely to die more rapidly compared to a person with subtype A. Ten percent of those infected with subtype D died within three years, while none with subtype A died. However, viral load ranged from 20,000 particles per cubic milliliter of blood to 100,000 particles per cubic milliliter of blood in those with both subtypes, and was not found to be an accurate predictor of rapid death within the same timeframe.

Participants in the study came from the Rakai cohort, a population of 12,000 people in Uganda who are being monitored to determine how HIV spreads throughout the country. More than 300 newly infected men and women participated in the study, conducted between 1995 and 2001, with 53 becoming infected with subtype A and 203 infected with subtype D. Another 70 were infected with a recombinant version of both subtypes. Even though the quantity of virus infecting these individuals was roughly the same for each subtype, average years of survival for each subtype differed widely: 8.8 years for A, 6.9 years for D and 5.8 years for AD.

Through annual blood tests, which were part of the study, the researcher knew when each person became infected. Once the diagnosis was confirmed, researchers used DNA tests to determine the HIV subtype, A and D being the most common in Uganda.

Researchers believe that subtype D is more virulent than subtype A because D has the ability to bind to key receptors on immune cells, allowing subtype D to kill more quickly. Additional blood analysis showed that with subtype A, the virus bound only to one kind of receptor, CCR5, to infect the cell. But 25 percent of subtype D virus bound to both CCR5 and another receptor, CXCR4. Indeed, two-thirds of those infected with CXCR4-binding virus died within three years.

According to the study's lead researcher, Oliver Laeyendecker, M.S., M.B.A., a senior research associate at The Johns Hopkins University School of Medicine and senior research assistant at the National Institute of Allergy and Infectious Disease, "Knowing a person's HIV subtype is important for the management of the infection because the disease can progress more rapidly in those infected with subtype D and recombinant virus incorporating subtype D than in those with other subtypes."

The Effect of HIV Subtype on Rapid Disease Progression in Rakai, Uganda. Oliver Laeyendecker, Xianbin Li, Miguel Arroyo, Francine McCutchan, Ron Gray, Maria Wawer, David Serwadda, Fred Nalugoda, Godfrey Kigozi, and Thomas Quinn.

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2006 Conference on Retroviruses and Opportunistic Infections, Feb. 5 - Feb. 9, Denver, Colo.

(Embargoed for release at 12:15 p.m. MT/2:15 p.m. ET, Monday, Feb. 6; oral presentation #44LB, Session 9, Ballrooms 5 and 6, Colorado Convention Center)


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