Infection by closely related HIV strains possible

A report of an individual infected with a second strain of HIV despite effective drug treatment following the first infection has researchers concerned.

“For the first time, we’ve shown it is possible for an individual to become infected with two closely related strains of HIV,” says Bruce D. Walker, M.D., a grantee of the National Institute of Allergy and Infectious Diseases (NIAID) and a researcher at Massachusetts General Hospital and Harvard Medical School.

Published in this week’s issue of Nature, these findings underscore the challenges vaccine developers face in creating a broadly effective vaccine against HIV. The first HIV vaccines may not prevent infection altogether, but rather may prevent HIV from causing disease by limiting the virus’ ability to reproduce, explains Dr. Walker. This case shows that a hypothetical vaccine against one strain of HIV may not necessarily protect the vaccinee against other, closely related strains.

“The implications of superinfection for an individual with HIV/AIDS are not yet clear,” says Anthony S. Fauci, M.D., NIAID’s director. “However, there is little doubt what these new data mean in terms of public health: It is imperative that safer sex be practiced during each encounter, even when both partners are HIV-infected,” he adds.

The new case involves a person whose HIV infection was kept in check for many months during structured treatment interruption (STI). In STI, antiviral therapies are frequently given during the early, acute stage of infection, but halted after the immune system has had time to adapt to the virus. Often, as in this case, a patient’s immune system rebounds enough to keep HIV suppressed. “This patient’s immune response against HIV was really quite robust,” says Dr. Walker. Thus, the researchers were perplexed when, after successfully suppressing HIV for close to one year, the patient’s viral load suddenly shot upwards. Despite several more attempts to interrupt therapy, the patient was unable to hold the virus to previously attained low levels.

To understand why STI stopped working for this individual, “We dissected the immune system in very fine detail,” says Dr. Walker. First, he and his co-investigators examined HIV-made proteins taken from the patient at several points in time. They detected a difference between the amino acid sequence of the original infecting virus and the virus isolated after STI failed. Additional studies confirmed that the change resulted from infection by a second HIV strain well after the first infection.

The two strains differed in overall amino acid sequence by about 12 percent, “about what we’d expect for two strains in North America,” notes Dr. Walker. In comparison, the sequence difference between strains of various major subtypes, or clades, of HIV is about 30 percent. Although superinfection by strains from different clades has been reported previously, this is the first published report of infection by two strains from the same clade.

The picture became still more sobering when the researchers compared only those HIV amino acid sequences targeted by the immune system. Here, the strains differed by 50 percent. Consequently, a large fraction of the immune cells that had been produced previously and that had successfully tamped down the first virus were unable to recognize and react to the second strain. “We were stunned,” says Dr. Walker. “Essentially, the immune system was encountering two markedly different viruses.”

The research did uncover a few bright spots, however. For instance, immune system cells called CD8+ T cells, appeared in new, strain-specific forms after the individual became infected with the second strain. This indicates an ability on the part of the CD8+ T cells to react appropriately to newly arrived HIV strains, even in conditions of chronic infection. Thus, researchers can remain cautiously optimistic that therapeutic immunization to create broader and more potent immune responses in persons with chronic HIV infection may one day be possible.

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: M Altfeld et al. HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature 240:434-39 (2002).