IDWeek 2015: Post-Treatment Control of HIV Appears Rare, Biomarkers May Help Predict Rebound

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Only 4 individuals out of nearly 5000 people receiving care at U.S. military health facilities were found to exhibit immune control of HIV after starting antiretroviral therapy (ART), achieving viral suppression, and interrupting treatment, according to a presentation at IDWeek 2015 this month in San Diego. A recently published related study identified several biomarkers that may help predict who will be post-treatment controllers, a useful tool for HIV cure research.

Post-treatment controllers (PTCs) are people with HIV who start antiretroviral therapy -- in some cases during acute or primary infection -- reach a very low or undetectable viral load, and then stop treatment, either as part of structured treatment interruption research or for other reasons such as patient choice or loss to follow-up. The French VISCONTI cohort is the most well known group of post-treatment controllers. Infants treated very early, like the Mississippi Baby, seem to be a different phenomenon, as are so-called "elite controllers" who maintain viral control without ever going on treatment.

Matthew Perkins from Walter Reed National Military Medical Center and colleagues from several other military health facilities around the U.S. aimed to determine how many post-treatment controllers were among participants in the HIV Natural History Study Cohort, which has followed HIV-positive patients since 1986 at 6 major military treatment facilities. Participants are seen about once every 6 months, at which time they undergo a physical exam, blood is collected for viral load testing, and their ART regimens is documented.

The researchers retrospectively analyzed medical records from 4685 cohort participants with Clade B HIV. The analysis was limited to 3480 people who had a pre-treatment viral load of at least 1000 copies/mL, indicating that they were not elite controllers. Within this group, 2115 had been on ART and had suppressed viral load (<400 copies/mL) for at least 2 years. Of these, 85 stopped ART and had an available viral load measurement done at least 30 days after treatment discontinuation.

Results

"The results of our study are consistent with the rarity of post-treatment controllers reported in the literature," the researchers concluded. "While our numbers are too small to suggest any associations between demographic characteristics or medical history and post-treatment control, it is interesting to note that all 4 post-treatment controllers were African American, 1 had previously been treated for lymphoma, and 1 was undergoing treatment for hepatitis C."

They noted that these are the first known reports of post-treatment control in people who started ART during chronic infection -- other post-treatment controllers identified to date, including the VISCONTI cohort and SPARTAC participants (see below), started ART very soon after infection.

"The existence of patients who spontaneously control HIV infection suggests that a functional HIV cure may be possible and investigations into these patient’s immunologic characteristics may yield clues to how this could be achieved," they suggested.

Biomarkers for Post-Treatment Control

In a related study, published in the October 9 edition of Nature Communications, Jacob Hurst and John Frater from the University of Oxford and colleagues looked for biomarkers that could help predict post-treatment control. These findings were previously presented in part at this year's Conference on Retroviruses and Opportunistic Infections.

The researchers analyzed outcomes in the SPARTAC trial, in which people with primary HIV infection either received immediate antiretroviral treatment lasting for 12 or 48 weeks, or else deferred treatment until their CD4 count fell below 350 cells/mm3.

They found that 3 markers of T-cell exhaustion -- PD-1, Tim-3, and Lag-3 -- measured prior to ART initiation strongly predicted the time to viral rebound.

"These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription," the study authors concluded. "Our results may open new avenues for understanding the mechanisms underlying post-treatment control, and eventually HIV-1 eradication.

"Our work has identified that there are certain markers on the immune cells of patients which seem to help predict who can stop therapy and stay well," Frater explained in a University of Oxford press release. "We hope now to find out more about these markers -- and others -- to discover if new strategies for treating or even curing HIV might be possible."

"We want to be able to predict how the virus will behave before we take patients off ART to test drug therapies aimed at eradicating HIV," Anthony Kelleher from the University of New South Wales added in a separate press release.

10/20/15

References

M Perkins, R Deiss, T Lalani, et al. Post-Treatment Control of HIV Infection in an Early Diagnosed Well-characterized Military Cohort of Chronically HIV-1 Infected Subjects. ID Week 2015. San Diego, October 7-10, 2015. Abstract 1072.

J Hurst, M Hoffmann, M Pace, J Frater, et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nature Communications 6:8495. October 9, 2015.

Other Source

University of Oxford. HIV: Researchers Find that "Biomarkers" Can Predict Virus Remission in Patients. Press release. October 9, 2015.

D Wheelahan, University of New South Wales. HIV Discovery: Biomarkers Predict Virus Return When Treatment Is Stopped. Press release. October 9, 2015.