HIV subtyping may be useful for management

April 2006

DENVER — HIV subtype may be a better predictor than viral load for determining if a patient will have a rapid progression to death from AIDS, according to research presented at the 13th Conference on Retroviruses and Opportunistic Infections.

Researchers from the Johns Hopkins University School of Medicine evaluated viral subtype as a predictor of AIDS death, considering patients’ viral load, and found that patients with HIV viral subtype D were likely to die more rapidly compared with those with subtype A: 8% of those with subtype D died within three years, while none with subtype A died, according to findings from a retrospective study conducted in Uganda.

Those with the recombinant viral subtype of both A and D were most at risk for death — 11% died within three years.

“Subtype D and recombinant strains incorporating subtype D are more pathogenic than subtype A as indicated by more rapid progression to disease or death,” said lead researcher Oliver Laeyendecker, MS, MBA, senior research associate at Hopkins and senior research assistant at the National Institute of Allergy and Infectious Disease.

Traditional testing standards help monitor the progression of HIV to AIDS by tracking viral load; less than 50 viral copies/mL of blood is considered suppressed disease and more than 75,000 copies/mL means that the disease will progress more rapidly.

Viral load was not found to be an accurate predictor of death within the first three years, although participant’s viral load did have a significant effect on disease progression over longer follow-up times, according to the study. Viral load ranged from 20,000 to 100,000 copies/mL of blood in those with both subtypes.

“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,” he added.

Studying HIV subtype

Laeyendecker and colleagues recruited participants through the Rakai cohort study, an annual population survey of 12,000 individuals from 50 communities in the rural Rakai district of southwestern Uganda who are being monitored to determine how HIV spreads. About 300 adults with newly acquired HIV between 1995 and 2001 were identified in this retrospective study.

Through annual blood tests, the researchers knew when each person acquired the virus. Laeyendecker and colleagues defined AIDS as a CD4 cell count less than 250, at which patients were then eligible for antiretroviral therapy. Once they confirmed diagnosis, they used DNA tests to determine the HIV subtype, A and D being the most common in Uganda.

The researchers determined subtype data with use of the MHAacd (Multiregion Hybridization Assay for subtypes A, C and D) and determined viral load with use of Roche Amplicore v1.5.

Findings indicated that 16% (53) of the participants had HIV subtype A, of which 38% were men between 23 and 35 years old; 60% (203) had HIV subtype D, of which 36% were men and between 25 and 26 years old; and 20% (70) had a recombinant version of both subtypes, of which 47% were men and between 24 and 38 years old.

Source: Oliver Laeyendecker, MS, MBA

Laeyendecker and colleagues conducted follow-up on AIDS progression and potential death between 1½ years to five years later. Five participants with subtype A developed AIDS and none died, and 40 participants with subtype D developed AIDS and 12 died. Ten participants with the recombinant virus developed AIDS, but 11 died.

Even though the quantity of virus in these individuals was roughly the same for each subtype, average years of survival for each subtype differed widely: 8.8 years for subtype A, 6.9 years for subtype D and 5.8 years for the recombinant. 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 among participants with subtype A, the virus bound only to one receptor, CCR5, to infect the cell. But 25% of subtype D virus bound to both CCR5 and another receptor, CXCR4. Two-thirds of the participants with the CXCR4-binding virus died within three years.

“Vaccine trials or trials of [highly active antiretroviral therapy] which assess disease progression as an endpoint must consider subtype differences,” he concluded.

For more information:

• Laeyendecker O, Li X, Arroyo M, et al. The effect of HIV subtype on rapid disease progression in Rakai, Uganda. Oral Abstract 44LB. Presented at: 13th Conference on Retroviruses and Opportunistic Infections; Feb. 5-8, 2006; Denver.