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Post-treatment control of HIV appears rare, biomarkers may help predict viral rebound
Liz Highleyman, 2015-11-04 08:10:00

Only four individuals out of nearly 5000 people receiving care at US 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 last 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 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 of Walter Reed National Military Medical Center and colleagues from several other military health facilities around the US aimed to determine how many post-treatment controllers were among participants in the HIV Natural History Study Cohort, which has followed people living with HIV since 1986 at six major military treatment facilities. Participants are seen about once every six months, at which time they have a physical examination, give a sample of blood for viral load testing and their ART regimen is documented.

The researchers retrospectively analysed 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 two years. Of these, 85 stopped ART and had an available viral load measurement done at least 30 days after treatment discontinuation.

Among the 85 people who stopped treatment, 81 experienced rapid viral rebound (>400 copies/ml) after ART discontinuation. But four individuals maintained viral suppression for six months or more off treatment. Of these, two were classified as ‘transient controllers’, having viral suppression for at least six months but less than two years, while the other two were ‘durable controllers’, having suppressed virus for two years or longer.

Three of the people with post-treatment viral suppression were men, all were black and their ages ranged from 21 to 38 years. All had started taking ART during chronic infection, about one to five years after seroconversion. Their pre-treatment viral loads were low: 1008; 2011; 35,454; and 46,773 copies/ml. All had viral loads <50 copies/ml at six months after treatment discontinuation.

The two transient controllers maintained viral suppression off ART for approximately nine months (267 days) and about a year and a half (575 days). One durable controller had suppressed virus for nearly three years (1058 days). The other restarted ART after more than two years (794 days), having not yet experienced viral rebound, because his partner wanted to become pregnant.

“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 four post-treatment controllers were African American, one had previously been treated for lymphoma, and one 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 patients’ immunologic characteristics may yield clues to how this could be achieved,” they suggested.