Investigators Uncover Details About A Rare Group of HIV Patients

SEPTEMBER 21, 2018
Jared Kaltwasser
Jonathan Li, HIV, antiretroviral therapyJonathan Z. Li, MD
A pair of new studies is shedding light on a rare, but scientifically important, group of people with HIV who are able to maintain viral control even after stopping antiretroviral therapy. Clues about this ability may help improve antiretroviral therapy, which currently most patients with HIV must receive for life.

These patients are known as post-treatment controllers (PTCs). They are defined as people who have viral loads of 400 or fewer copies per milliliter of blood plasma at least 24 weeks after cessation of therapy.

A recent study looked at 67 post-treatment controllers in an attempt to locate any similarities or correlations that might suggest which patients are likely to become PTCs. The researchers found that in the majority (n = 38) of cases in which a patient became a PTC, the patient started ART soon after infection. Of the 67 patients, just over half—55%—maintained viral control at 2 years. About 1 in 5 still had viral suppression at 5 years.

Lead author Jonathan Z. Li, MD, of Brigham and Women's Hospital's Infectious Disease Clinic, told MD Magazine® that early treatment appears to be an important factor in determining the odds that a patient will be a post-treatment controller.

“[I]n addition to the individual and public health benefits of early antiretroviral therapy initiation, we’ve now found that it increases the chances of sustained HIV remission,” he said. “Waiting to start ART will decrease their chances of becoming a post-treatment controller.”

In a second study, on which Li was also the lead author, researchers sought to gain a better understanding of the biological mechanisms at play in post-treatment controllers. To do so, they sequenced viral DNA from 10 PTCs and 16 post-treatment non-controllers (NCs).

The sequencing showed that PTCs had smaller viral reservoirs, meaning they had less intact viral DNA prior to treatment interruption.

“Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups,” Li and colleagues wrote. “Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells.”

The research could prove important as it suggests strategies by which scientists can work to improve viral suppression, potentially ending the current paradigm where the vast majority of patients must continue taking ART for the rest of their lives.

Notably, this research represents the largest study to date of PTCs, a group that is difficult to quantify and identify. PTCs are believed to be rare, and thus Li and colleagues had to search for PTCs among patients who had participated in 14 earlier studies that involved treatment interruption.

Just how many PTCs—or potential PTCs—are out there remains an open question, Li said. “While we do not generally recommend stopping ART for our patients outside of a clinical trial, it’s definitely possible that there are other post-treatment controllers who stopped ART on their own and are not engaged in care,” he said.

The first study, which identified the correlation between early treatment and PTC status, “The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies,” was published in The Journal of Infectious Diseases. The second study, on the biological mechanisms underlying post-treatment control, “HIV-1 proviral landscapes distinguish post-treatment controllers from non-controllers,” was published in The Journal of Clinical Investigation.

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