A recent clinical trial, known as the SETPOINT study, by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health (NIH), found that the immune system of untreated HIV-infected individuals weakened earlier than previously proposed.

Tia Fraizer, M.D., and Larry Fox, M.D., medical officers in the Division of AIDS at NIAID, said, “It is possible that the finding that the immune systems of untreated HIV-infected individuals appear to deteriorate faster than previously thought may lead some clinicians to monitor the immune health of patients with recent HIV infection more closely.”

The study compared the viral setpoint, the point at which the amount of HIV in the blood levels off, in two groups of individuals with recent HIV infection that differed in treatment. The viral setpoint is significant because it is thought to be related to the severity of the HIV disease. Additionally, the researchers wanted to observe whether early treatment in recently infected individuals lowers the viral setpoint.

One group received a 36-week course of antiretroviral therapy (ART), while the other group received no treatment until they met the current immunologic, virologic, or clinical requirements for starting ART.

At the conclusion of the study, the difference in viral setpoint was not successfully evaluated due to an insufficient number of viral setpoints measured. However, the results showed that the CD4 cell (white blood cell) count declined much faster in the group that received no treatment than in the group that did receive treatment.

Currently, it is thought that individuals with untreated HIV infection lose 60 CD4 cells per microliter each year. U.S. guidelines recommend starting ART when CD4 cell count drops below 350 cells per microliter, which suggests that only after 2-3 years would individuals need treatment. Yet, results of the study showed that 20 of the 39 individuals in the no treatment group fit the guideline and needed treatment within one and a half years.

The trial has been stopped ahead of schedule after a review from an independent data and safety monitoring board (DSMB) determined that further findings would no longer change the outcome of the study or add significant information. The DSMB also found that more than half of the untreated group needed to initiate continuous ART before the viral setpoint could be measured at 72 weeks.

Because the SETPOINT study included only a relatively small number of HIV-infected individuals, additional studies may need to be completed to further confirm the results. Fraizer and Fox said, “The finding that the immune systems of untreated HIV-infected individuals appear to deteriorate faster than previously thought needs to be validated through close observation of a much larger population of people with recent HIV infection.”

Currently, the study team is working with the participants who were introduced to ART during the trial to ensure that they can transition to clinical treatment outside of the trial. Also, following DSMB’s recommendation, the team is also offering up to 36 weeks of ART treatment for the participants who had already started treatment during the trial.

“We are currently supporting studies that evaluate the impact of early treatment on HIV infection. In addition, we are planning to analyze existing observational data to determine if other groups of HIV-infected individuals also experienced a similar accelerated progression of disease as found in the SETPOINT study,” said Fraizer and Fox.

For more information, please see the SETPOINT trial at the clinical trials Web site or the NIH press release.