Written by Jeannie Wraight
March of 2013 at The Conference on Retroviruses and Opportunistic Infections
(CROI 2013), scientists announced a baby girl in Mississippi was found to have
cleared HIV through the use of antiretroviral therapy initiated within 36 hours
after birth. This case drew a great deal of controversy, partially due to the
media dubbing the baby 'cured of HIV'. Most involved in the case, and in HIV
science and medicine, now call this baby a case of 'HIV remission'. Whether or
not the Mississippi baby was indeed 'cured' of HIV, the case did bring
significant attention and momentum to research into the very early initiation
of ARVs in newborns.
Mississippi baby's doctor, Deborah Persaud has continued to examine whether
very early initiation of ARVs could promote HIV remission in other babies
perinatally-infected with HIV.
CROI 2014 Dr. Persuad presented data on a second child, this one from
California, who was also provided ARVs very soon after birth with the same
results as the Mississippi baby. The
child was confirmed HIV positive at 4 hours post-birth and was given
zidovudine/lamivudine (Combivir) and nevirapine (Viramune). Lopinavir/ritonavir
(Kaletra) was then added at 2 weeks and the full combination was given until
3.4 months of age. A viral load of 32 copies/mL was seen at day 6 which dropped
to undetectable at day 11. At 9.5 months, the child was still receiving
zidovudine/lamivudine and nevirapine and continued to have an undetectable
2.2 months, the California baby tested negative for HIV using an HIV DNA test.
She then tested negative using a Western blot test at age 9 months. Despite the
negative HIV results, both children show very low levels of persistent proviral
DNA. The relevance of the detection of the proviral DNA is still unclear.
positive results of both of these children has helped spur the momentum for
further studies. Clinical trials will begin shortly providing ARVs to newborns
of HIV positive women who were not on antiretroviral therapy during their
pregnancy. These infants will be given therapeutic doses of ARVs immediately
following birth, instead of the smaller doses that are normally given during
and after labor and birth.
goal would be to prevent the establishment of HIV proviral reservoirs. During
initial HIV infection, some cells are infected with HIV but become inactive and
do not replicate. This essentially hides them from the immune system and makes
them unreachable to ARVs. It is thought that if ARVs are started immediately
following birth that these reservoirs may be prevented from forming.
Persaud presented an abstract entitled "Virologic Control by 1 Year of Age
Significantly Reduces HIV-1 Reservoirs in Perinatal Infection," in which
she and colleagues tackled the questioned of how much could the proviral
reservoirs be reduced in perinatally-infected children. This study is a step
towards finding some of the answers we seek regarding latent reservoirs and early
and colleagues examined proviral viral load in peripheral mononuclear cells
(PBMCs) in 144 perinatally-infected children (PHIV) enrolled in the Pediatric
HIV/AIDS Cohort Study/Adolescent Master Protocol (PHACS/AMP). The children had
been receiving antiretroviral therapy for a median of ten years. At the time of
Persaud's study, the children were 8 to 20 years of age.
compared proviral burden, HIV serostatus, 2-LTR circles, and immune activation
markers (soluble CD14, CD163, IFN-?, IL-6, and IL-1ß) by age at virologic
control (less than 1 year, verses 1-5 years, verses greater than 5 years of
age). In addition, proviral burden was correlated with HIV serostatus and 2-LTR
circles and immune activation markers and compared in perinatally-HIV-exposed,
uninfected (PHEU) children and perinatally infected children (PHIV).
showed that 46% of the children who suppressed viral load by age 1 compared to
11% of the children who suppressed viral load after age 1, had undetectable
viral loads of less than <4 copies/million PBMC's. In addition, lower
proviral burden was associated with undetectable 2-LTR circles (p<0.001) and
HIV-1 seronegative/indeterminate status (p<0.001).
were similar across all three groups of virological control for plasma
concentrations of soluble CD14, CD163, IFN-?, and IL-1ß, however sCD14 and IL1
ß levels were significantly higher in PHIV+ children than in PHEU (p<0.001
and p=0.004 respectively).
authors concluded that, "Achieving virologic control by one year of age in
perinatal infection leads to significantly smaller proviral reservoirs in those
with HIV-negative or indeterminate serostatus and absent 2-LTR circles. It does
not reverse immune activation. These findings emphasize the benefits of early
therapy in perinatal infection with implications for a viro-immunologic profile
for HIV cure-related clinical trials."
is clear that 'curing' HIV or inducing remission of HIV, similar to what we see
in cancer patients, will involve strategies directed at individual populations
and not an all-in-one 'cure' for all people with HIV. Only time will tell
whether these two children and other immediately treated perinatally-infected
children will remain HIV-positive but it does appear that we are on the right
Control by 1 Year of Age Significantly Reduces HIV-1 Reservoirs in Perinatal
Persaud et al
CROI 2014 Boston,
Massachusetts March 3-6, 2014. Abstract #72 page 146