Seroreversion possible, but rare, after early treatment of acute HIV infection

Early treatment of acute HIV infection resulted in loss of HIV-specific antibodies or ‘seroreversion’ in three of 150 patients treated at two Boston hospitals, according to a study published in the 15^th March edition of Clinical Infectious Diseases.

Although it does not indicate that the three patients were cured of their HIV infection, this finding does demonstrate that early control of HIV can alter the body’s immune response to the virus in a minority of patients. However, the significance of this finding for the patients’ future health and medical care remains uncertain until the results of future studies are available.

Soon after HIV infection, the body usually responds by producing specific HIV antibodies. These antibodies bind to HIV particles in the blood, targeting them for removal by the immune system. This helps to control viral loads during the ‘chronic phase’ of HIV infection.

This observational study was carried out to assess the impact of treating recently infected HIV-positive patients with highly active antiretroviral therapy (HAART) on the production of HIV antibodies.

One hundred and fifty patients were included in the eight-year study. All had symptomatic acute HIV infection or were confirmed to have been infected with HIV for less than a year. Three of these patients, who began treatment between one and 16 days after seeking medical care, did not develop fully evolved HIV antibody responses or exhibited partial or complete seroreversion over 40 to 56 months of follow-up.

All three patients exhibited virologic suppression two to six months after starting treatment, and seroreversion occurred seven to 26 months after starting treatment. All three had an undetectable viral load when seroreversion occurred.

“Early antiretroviral therapy associated with durable virologic suppression in acute HIV-1 infection may abrogate the formation or detection of HIV-1-specific antibodies,” conclude the investigators. “Ongoing antigenic stimulation may be required to maintain HIV-1-specific humoral responses.

“Incomplete evolution of the HIV-1 antibody response and / or presence of seroreversion (although infrequently observed) underscore the potential unique immunologic effect of early antiretroviral therapy in patients with primary HIV-1 infection.”

Previous reports have described seroreversion in uninfected infants who received HIV antibodies from their HIV-infected mothers, and in patients with advanced immunosuppression. In infected patients, loss of HIV antibodies may be associated with more rapid disease progression in the absence of antiretroviral therapy, since the immune system’s controlling effect on the virus is absent.

In an accompanying editorial commentary, Elizabeth Cornick of the University of Colorado Health Sciences Center writes, “it is conceivable that treated HIV-1-infected seroconverters who undergo seroreversion may be more vulnerable to recurrence of acute retroviral syndrome upon cessation, because of low levels of both cellular and humoral immune responses.”

All three seroreverting patients remained on antiretroviral therapy at the end of this study.

Cornick also warns that the loss of HIV antibodies should not be confused with clearance of HIV itself. “It is critical that both physicians and patients understand that seroreversion does not indicate viral eradication in individuals who were treated after onset of primary HIV-1 infection.”

However, she acknowledges that, “the report by Kassutto et al. represents the largest number of cases and the most convincing evidence to date that incomplete antibody evolution or seroreversion following treatment of primary HIV-1 infection occurs, albeit infrequently.”