Editorial :
Recent
progress in HIV
research has directed global scientific community to search for a cure for HIV infection.
The first evidence emerged from Timothy Brown, a Berlin patient. This
HIV-infected patient received hematopoietic stem cells from an HLA-matched
donor whose genome naturally lacked CCR5, the major receptor of HIV. Mr Brown
appears to be cured of HIV as well as leukaemia
as no infectious virus could be recovered from his blood and other tissues for
over 6 years after the stem
cell transplantation. The case has given direction to scientists to
administer genetically modified stem cells lacking CCR5
receptors to HIV-infected person to provide a defence against HIV. However,
this approach may be difficult to apply to all HIV infected persons globally. The
second clue towards HIV cure came from a Mississippi infant, initiated ART at 31
hour of age for a period of 18 months who subsequently had undetectable plasma viral
load for 27 months without ART. However, unfortunately the baby now at the age
of four years have been detected HIV infected. The case nevertheless has given guidance
to researchers to initiate ART very early in acute
infection to reduce the size of HIV reservoir and achieve a long-lasting
drug-free viral
suppression (functional cure). Trials are in progress in Thailand that
showed remarkable reduction in reservoir size following very early ART. However, the resurgence
of HIV after several years of discontinuation of ART suggests that the
reservoir has been persisting though undetected that need to be tackled by
innovative approaches. TAT is one of the first proteins produced by HIV infected
cells that facilitate amplification of replication of HIV. Without TAT, the HIV-infected
cells only produce new viruses very sluggishly. Didehydro-cortistatin
A(dCA), a potent TAT inhibitor, has been discovered by Scientists at the
Scripps Research Institute in California, which have potential to maintain the
reservoir cells in a lifelong sleep such that no residual HIV replication is
left. However, further research will be needed to understand therapeutic uses
of dCA. While CD4+
cells are the important reservoir and infected CD4+ cells undergo natural
death, several studies have shown the presence of HIV in long-lived monocytes/
macrophages,
follicular dendritic cells, and cells of various organs. These cells can replicate
the virus
at a low level and not undergo any cell death. Hence to advance towards a cure,
such viral reservoirs need to be taken to task by so called “kick and kill”
strategy. Romidepsin, a Histone Deacetylase (HDAC) inhibitor, reactivate latent
virus in the resting cells. Once the virus is “woken up” and starts replicating,
it becomes visible to the immune system and is susceptible to antiretrovirals.
However, HDAC inhibitors have unpredicted immune-suppressant effects. The efforts to find an
effective HIV vaccine have not been fruitful so far and require further
continuous research. Hence the world scientific community has very rightly started
searching for a cure for HIV-infection. Till then it is essential on our part
to consolidate whatever we have gained so far through evidence based HIV
research. The UNAIDS
target of 90-90-90, which aims to diagnose 90% of people with HIV, treat 90% of
people diagnosed with HIV and achieve undetectable viral load in 90% of people
on treatment by 2020 should be given due emphasis and evidence based Option B+
PMTCT, PrEP and TasP approaches should be implemented globally. CD4 cells, HIV transmission, ART, Monocytes, MacrophagesTowards an HIV Cure - a Myth or a Reality
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