Elite suppressors of HIV to change how scientists monitor spread of disease

Aug 15 2006

Scientists at Johns Hopkins have found that 1 percent to 2 percent of those infected with HIV in Baltimore apparently suppress the virus to nearly undetectable levels on their own, confounding public health efforts to accurately monitor the pandemic's spread, now in its 20th year.

The city's health department estimated in 2004 that nearly 14,000 residents are infected.

These so-called elite suppressors of the virus are scientifically almost indistinguishable from new cases of the disease, researchers say, because they have low blood concentrations of antibodies to HIV. The scientists note that these low viral blood levels could result from use of antiretroviral therapy or because of genetic variations that give some people especially strong immune systems, which result in lower concentrations of antibody to HIV when the virus is suppressed. Those with weaker immune systems are also more likely to have already died, leaving behind a greater proportion of those with stronger immunity.

The Hopkins study tested blood in 1,549 patients who came to The Johns Hopkins Hospital emergency room between June and August 2001. All were screened for HIV using the current gold standard, serological testing algorithm for recent HIV seroconversion, or STARHS for short. STARHS is widely recommended by the U.S. Centers for Disease Control and Prevention, and the test relies on differentiating newly infected from chronically infected people based on the amount of HIV antibodies present. Normally, the antibody concentration to HIV increases over time during the first six months of infection.

Some 183 tested positive (12 percent), including 35 who did not know they were infected. Of those who tested positive, 11 were identified by STARHS as newly infected because they had low levels of antibodies to HIV. However, when researchers added a second test to measure the strength of antibody-antigen binding in the immune system's response to HIV infection, they found only six new infections. In the second test, called Affinity/Avidity, an immature response from a new infection produces weak binding, whereas a mature infection involves strong binding.

Additional blood testing for the presence of antiretroviral drugs revealed that two samples were from patients who had already begun treatment, explaining why they had suppressed the virus. This left researchers with three inexplicable cases of strong viral suppression and the likely conclusion that they were elite suppressors. Additional evidence came from comparing the remaining blood samples to eight others from previously known elite suppressors in Baltimore. Tests showed similar results - low antibody levels, strong antibody binding to virus, less than 50 copies of the virus per cubic milliliter of blood, and no antiretrovirals present - affirming their original suspicion of elite suppression.

Lead researcher Oliver Laeyendecker, M.S., M.B.A., a senior research associate at The Johns Hopkins University School of Medicine, says the emergence of elite suppressors creates confusion for those responsible for monitoring new infections and spread of HIV. He adds that new testing algorithms, in addition to STARHS and Affinity/Avidity, will have to be developed to accurately discount any artificially "new" cases of the disease, especially as the disease enters its mature phase on a global scale and as the developing world gains increased access to antiretroviral therapies.

The Effect of Viral Suppression on Cross-Sectional Incidence Testing, the 2001 Johns Hopkins Hospital Emergency Department Sero-Survey as an Example. Oliver Laeyendecker, Charlamine Henson, S. Michele Owen, Bobbi Jo Horne, Richard Rothman, Gabor Kelen, Kerrunne Ketlogetswe, Judy Shahan, Renu Lal, and Thomas Quinn.