Another case of prolonged control of HIV
replication after stopping treatment was reported on Tuesday at the 7th
International AIDS Society conference (IAS 2013), indicating that cases of post-treatment
control of HIV are not confined to the French VISCONTI cohort.
The report is likely to be joined by others
in months to come after the organisers of the VISCONTI cohort appealed today
for researchers worldwide to join them in identifying people with HIV who are
able to control viral replication at undetectable levels after stopping
treatment – so-called 'functional cures'. The cases are described as 'functional' cures because although HIV is not eliminated from the body, it is failing to replicate, a condition also described as 'remission' by many researchers.
...although HIV is not eliminated from the body, it is failing to replicate, a condition also described as 'remission'.
The case involves a 67-year-old German man
who probably acquired HIV in the summer of 1999 through sexual
transmission. At the time of diagnosis he tested positive for HIV antibodies on
an ELISA test and tested positive for several HIV protein bands on a Western
blot test, an indication of very recent infection.
At the time of diagnosis he had a viral
load above 1 million copies/ml and a CD4 cell count just below 500 cells/mm3.
He initiated antiretroviral therapy with
AZT, 3TC and efavirenz just under three months after exposure to HIV and within
one month of confirmed seroconversion, after an acute viral illness.
His viral load was suppressed below the
limit of detection very quickly and he experienced only two small rebounds in
viral load above 10 copies/ml, around two years after starting treatment and
140 weeks into his course of treatment. Throughout this period his CD4 cell count remained stable in the range
900 to 1000 cells/mm3.
the patient chose to undergo a treatment interruption, at which time he
experienced a small viral rebound (above 10 copies/ml but below 100 copies/ml)
before regaining viral control within three months of stopping treatment. HIV
has remained undetectable ever since and he shows no evidence of HIV
DNA in peripheral blood mononuclear cells (PBMCs), nor any evidence of HIV RNA
(indicating viral replication) in cerebrospinal fluid.
Use of an ultra-sensitive assay capable of
detecting viral load as low as 1 copy/ml failed to detect any HIV RNA. A viral
co-culture DNA-PCR was similarly unable to detect any HIV DNA.
The patient’s immunological and virological
characteristics were examined in detail. These were compared to HIV-negative
patients and nine so-called “elite controllers” – people with HIV who
maintain a normal CD4 cell count and low viral load without the need for
In contrast to some other reported cases of
HIV control after stopping treatment – described as 'remission' by some
researchers, and as a functional cure by others – the case study reported today
shows evidence of strong and broad CD8 T-cell responses and strong
proliferative CD4 T-cell responses.
Analysis of the CCR5 co-receptor showed
that the homozygous CCR5 promoter A59029G was present but no delta 32 deletion
was present – a characteristic
associated with slower HIV disease progression. The HLA-I subtype was A 01, 02
Neither HIV RNA nor p-24 antigen was
detected in gut tissue.
ELISPOT showed a strong polyfunctional CD8 cell
response against both gag and nef epitopes as well as polyfunctional
HIV-specific response and a normal distribution of effector memory T-cells and
central memory T-cells. These were comparable to elite controllers.
The frequency of peripheral Treg and Th17
cells was similar to those observed in HIV-negative individuals and elite
Nevertheless, HIV was recovered in the
laboratory using a humanised mouse model after transplantation of the patient’s
purified CD4 T-cells and anti-CD3/CD28 stimulation. This indicated the presence
of HIV capable of replication.