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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
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
“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.