BOSTON—Early administration of highly active antiretroviral therapy (HAART) greatly enhances immune control of viral load in patients infected with the human immunodeficiency virus (HIV). By stimulating immune responses with increased exposure to the virus, drug therapy interruption may further enhance immunity. However, a case study shows that even patients who respond well to this regimen may remain vulnerable to subsequent reinfection with a second strain of the virus.[1] Superinfection in the presence of apparently strong immunity suggests that the virus’ extensive variability must be considered in developing a universal HIV vaccine.

A sudden weakening of viral control in a patient who had previously exhibited a robust immune response after receiving early HAART prompted Bruce Walker, MD, Director of the Partners AIDS Research Center at Massachusetts General Hospital, and colleagues to investigate. Careful immunological analysis and exploration of the patient’s history suggested infection with a new strain of the virus.

HIV’s preference for activated T cells impairs development of an HIV-specific helper–T-cell response. “As the particular subset of CD4+ cells is mobilizing to try and fight HIV, … those very cells are making themselves available to become infected,” explained Dr. Walker, who is also a Professor of Medicine at Harvard Medical School. A current strategy, therefore, is to administer HAART at the earliest stages of infection to attenuate viral attacks on immune cell populations recognizing HIV, dramatically altering the course of the disease.

Early treatment usually yields strong immune responses. But by lowering HIV titers, continued HAART also limits stimulation of virus-specific cells. Would control persist even if HAART were interrupted? “When we stopped therapy, some of [the patients] went on to control the virus on their own,” said Dr. Walker. “That brief reexposure to the virus resulted in a dramatic increase in immunity to HIV.” In some patients, viral titers were controlled for more than a year without HAART.

In one such patient, however, viral titers suddenly climbed. Careful blood work and viral genetic analysis revealed a new infection. “Even though we had a very strong immune response against the initial infecting strain of virus, [the patient] had had unprotected sex, and he got infected with a second strain,” Dr. Walker clarified. “What was surprising,” he pointed out, “was that it was superinfection with a very similar strain of virus.” The patient, he stressed, “was completely controlling one virus, and yet that amount of immunity was not enough to protect him.” Thus, control of viral titers does not signal invulnerability to reinfection. Said Dr. Walker, “Partners who are both HIV infected should still practice safe sex.”

“Vaccine strategies right now are targeted toward developing strong CD8+ responses that will … attenuate the disease course,” explained Dr. Walker. But, he emphasized, “Every infected person has a virus that is distinct from the next person’s—like fingerprints. What we’re trying to do is to create a vaccine to all of those strains, and it’s possible, but the challenge is going to be great.”

—Mimi Zucker, PhD

Reference
1. Altfeld M, Allen TM, Yu XG, et al. HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature. 2002;420:434-439.

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