Researchers in the United States say that they have
identified a case of a 'functional' HIV cure in a child infected with HIV who
began antiretroviral treatment within days of birth. The child has now been off
treatment for a year, and although HIV DNA has been detected at very low levels
in the child’s cells, the virus is not reproducing.
Further follow-up will be required to determine whether this
state persists, or whether viral replication resumes, but researchers involved
in the case are optimistic that what they have found represents a functional
cure – a state in which HIV remains in the body, but no longer replicates. One
functional cure in an adult has been reported previously – the so-called 'Berlin patient' (see below and related
The findings were presented at a press conference on the
opening day of the 20th Conference on Retroviruses and Opportunistic
Infections (CROI) in Atlanta, and further details were released on Monday 4 March in a
conference session on 'HIV Eradication'.
"We believe this is our Timothy Brown moment." Deborah Persaud, Johns Hopkins University School of Medicine
Dr Deborah Persaud of Johns Hopkins University School of
Medicine, Baltimore, reported on the case of a child treated with
antiretroviral therapy from 30 hours after birth, almost immediately after testing
for HIV DNA and RNA on the second day of life. The child was born to a mother with detectable viral load
at the time of delivery.
The child was delivered prematurely, at 35 weeks of
gestation, and the mother underwent rapid antibody testing for HIV at the time
of delivery. She had not been in HIV care previously. The child was tested for
HIV at around 30 hours of life, and tests revealed detectable HIV DNA and HIV
RNA of just under 20,000 copies/ml. RNA tests continued to be positive up until
20 days of life, indicating that this was not an isolated false positive result
and that viral replication was taking place.
In line with recommended practice in cases where mothers
have detectable viral load at the time of delivery, the infant was initiated on
a regimen of AZT/3TC and nevirapine as prophylaxis against infection. In cases
of prophylactic treatment to prevent infection in HIV-exposed infants, this
regimen would be given for 4 weeks. In this case, because virus was detected
and the infant had confirmed HIV infection, treatment continued until the age
of 18 months (although lopinavir/ritonavir (Kaletra)
was substituted for nevirapine at day 7). At 18 months of age, the child’s
caregiver withdrew the child from treatment and the child was lost to follow-up
for nearly six months.
Viral load tests were carried out at 7, 12 and 20 days of
age that showed detectable virus after the initiation of treatment, before the
virus became undetectable on a test with a lower limit of detection of 20
copies/ml at day 29. Subsequent testing until month 26 showed that viral load
remained persistently undetectable after this point, despite the fact that
treatment was stopped after 18 months.
When the child returned to care at 23 months of age and it
became apparent that viral load was not detectable in the absence of treatment,
clinicians at the University of Mississippi Medical Center sought advice from
research groups outside the state, including Dr Katherine Luzuriaga at the
University of Massachusetts.
Collaborating laboratories at the National Institutes of
Allergy and Infectious Diseases and the University of California San Diego
carried out ultrasensitive tests to determine whether HIV had been eliminated,
or whether any traces of the virus persisted in any cell types. They found that
viral RNA of 1 copy/ml could be detected in tests carried out when the child
was two years of age and 2 copies/ml at 26 months. Co-culture of 22 million resting CD4 cells
failed to identify any replication-competent HIV at 24 months.
However, testing at 24 and 26 months of age found a
reservoir of presumably latently infected cells: HIV DNA was detected in
peripheral blood mononuclear cells at a frequency of 37 and 4 copies per
million cells. The investigators also looked for 2-LTR circles, fragments of
unintegrated HIV DNA that might have the potential either to influence the way
in which the infected cell evades immune surveillance, or to establish a
prolonged state of latency. They found no 2-LTR circles within the cells
containing HIV DNA, suggesting that HIV is completely quiescent, and not
replicating – a functional cure of HIV infection.
Speaking at the press conference, Deborah Persaud rejected
suggestions that the case might represent an episode of successful
post-exposure prophylaxis, noting that several blood samples taken during the
first week of life had tested positive for viral RNA, indicating that infection
had already become established. However, further testing of these samples is
not possible because the samples had not been stored, their future significance
not being appreciated at the time the child was diagnosed.
Dr Persaud said that the findings represented a “proof of
concept”. Referring to the case of a Berlin man who was declared cured of HIV
infection following a bone marrow transplant from a donor with genetically
conferred resistance to HIV infection, she said: “We believe this is our
Timothy Brown moment.”
She said that trials to investigate whether a functional
cure is possible for larger numbers of infants are now in design, and that, if
successful, the challenge will be to replicate the results through the existing
platform of services for prevention of mother-to-child transmission.
Note: this is an
updated version of a report published on Sunday 3 March, and contains further
details of the case as presented at the conference on 4 March.