Viral load and viral DNA fall rapidly in infants who begin
antiretroviral therapy (ART) within days of birth, two South African studies have
found, showing the potential for clearing the reservoir of HIV-infected cells –
but infants with such a dramatic response to treatment may be a minority. The
findings were presented on Tuesday at the Conference on Retroviruses and
Opportunistic Infections (CROI 2017) in Seattle.
Clearing the reservoir of HIV-infected cells is considered
to be essential for developing an eventual cure for HIV infection, whether in
the form of complete elimination of the virus or in the form of long-term viral
control without medication, known as a functional cure.
The potential to eliminate HIV infection in infants treated
soon after birth was first reported in 2013, when researchers discovered that a
baby treated with antiretrovirals within days of birth appeared to have cleared
HIV infection. The so-called “Mississippi baby”, identified by doctors in the
US state, after her mother tested positive for HIV at the time of delivery,
showed no traces of HIV when tested 23 months after birth and five months after
But, in this case, HIV eventually reemerged. At
the age of three years and nine months, testing revealed that HIV was
detectable and that it was identical to the virus isolated at the time of
diagnosis, ruling out any possibility of reinfection.
Researchers have subsequently begun to investigate if the
disappearance of HIV in infants treated soon after birth is common, and whether
any infants experience complete disappearance of HIV DNA. In the case of the
Mississippi baby, HIV DNA remained detectable at a very low level. If HIV DNA
became persistently undetectable, it might indicate that HIV treatment has
eliminated the pool of HIV-infected cells and that the risk of viral rebound
after stopping treatment would be low.
HIV DNA is integrated into immune system cells and may
remain inactive, or latent, without producing new virus, for the lifetime of
the cell. If the cell is triggered to respond, HIV DNA will be triggered to
produce new virus.
The reservoir of cells containing HIV DNA becomes
established soon after infection, so to give the best chance of reducing or
clearing HIV DNA in infants, researchers believe that it will be necessary to
identify and treat infants within days of birth.
Kirsten Veldsman of Stellenbosch University reported on changes
in HIV DNA in infants who were treated with ART within eight days of birth at
Tygerberg Children’s Hospital. She described HIV RNA and DNA kinetics in five
infants. In three infants, HIV RNA declined to less than 100 copies/ml within 3.3 months; in the two remaining infants, HIV RNA fell below 100 copies after 6.3 and 6.7 months respectively.
HIV DNA fell very rapidly in the first 15 days of treatment, before entering a more gradual decline. The median rate of decay was -2.3 log per month, indicating that HIV DNA diminished by 200-fold in each month of treatment.
Kirsten Veldsman observed that HIV DNA was cleared much more
quickly in infants than in adults, possibly due to the much faster turnover of
CD4 cells in infants, and that the second, slower phase of decay nevertheless
occurred at a faster pace in those who started treatment within eight days of
birth when compared to those who started treatment later.
But how common is such a rapid response to treatment?
Another South African study reported on changes in viral load after infants
were initiated on treatment in the first month of life.
South African and US research group has been following infants initiated on ART
soon after birth at Rahima Moosa Mother and Child Hospital in
Johannesburg. Infants are tested with point-of-care viral load test (HIV Xpert)
on weekdays if staff capacity permits, or as soon as possible through a laboratory
viral load test, and then start treatment as soon as possible if positive for
To date the clinic has identified HIV infection and
initiated treatment in 75 infants as a result of immediate post-delivery
Just under half
of these infants started ART within the first two days of life (n = 30), and
Louise Kuhn of Columbia University Medical Center reported on early viral load
changes in this group of infants. HIV RNA (viral load) was tested at weeks 1,
2, 4, 8, 12, 16, 20, 24, 32, 40 and 48. HIV qualitative PCR, used to check for
the presence of HIV RNA in the absence of HIV antibodies in recently infected
people, was carried out prior to treatment and at weeks 24 and 48.
The research group found huge variation in viral load responses.
Although one-third of infants did achieve undetectable viral load, this took
anywhere from 90 to 330 days, and in the remaining infants viral load either
rebounded after initial suppression or never fell below the limit of detection.
In three infants, HIV RNA ceased to be detectable by qualitative
PCR. Dr Kuhn explained, “If they presented for HIV diagnosis, they would test
negative for HIV.” Whether this change is also apparent in HIV DNA levels
remains to be determined by further tests still being analysed.