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welcome back to health awareness today
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we're diving into a crucial topic the
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ongoing fight against HIV one and the
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role of toll-like receptors tlr in this
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battle HIV one is classified as a viral
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species within the family retrovir A
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subfam oror retrovir A and genus
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lentivirus this category also includes
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HIV 2 and the Simeon imuno deficiency
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virus SIV which infects non-human
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primates and serves as an essential EXP
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experimental model for HIV Immunology
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Vivo according to the Joint United
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Nations program on HIV AIDS unad data
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for 2021 there were 37.7 million 45.1
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million 45.1 million 45.1 million people
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living with HIV AIDS at the end of 2020
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the majority of these individuals live
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in eastern and southern Africa with an
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estimated 20.6 million ranging from 16.8
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ion despite a significant reduction in
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the number of new hiv1 infections over
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the last decade 1.5 million 1.0 million
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2.0 million 2.0 million new infections
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occurred during 2020 including 150,000
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infections in children under 15 years of
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age despite effective anti-retroviral
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therapies infection with this virus led
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to an estimated 680,000 480,000 480,000
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1.0 million deaths in 2020 emphasizing
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the need for continuous efforts to
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develop feasible strategies to treat
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these infections and to create an
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vacine although 40 years have passed
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since the isolation of HIV one by Bar
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ci8 L in 1983 and despite significant
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achievements in basic and clinical
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science innate and specific immunity to
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HIV one remains an exceptionally
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research currently HIV treatment is
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based on a combination of
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anti-retroviral drugs from several
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classes designed to Target various
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stages of the virus replication cycle
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these include reverse transcriptase
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Inhibitors protees Inhibitors Integra
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strand transfer Inhibitors capsid
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Inhibitors entry Inhibitors such as the
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fusion Inhibitors such as the fusion
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inhibitor infu tide and ccr5 inhibitor
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marok attachment Inhibitors and a CD4
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directed post attachment inhibitor
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anti-retroviral therapy art is
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exceptionally successful in reducing the
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intensity of viral replication but fails
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to eradicate the virus and is unable to
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cure infected individuals to date only
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some individuals have been cured of HIV
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one infection using stem cell
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transplantation from CCR 5 Delta 32
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donors even in successfully treated
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patients HIV establishes latent
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reservoirs most frequently in memory CD4
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plus t- cells where it remains in a
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dormant State invisible to the immune
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system the presence of a latent viral
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Reservoir is the key obstacle to curing
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HIV several therapeutic strategies
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including the a shock and kill approach
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aim to activate hiv1 replication in
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latently infected cells allowing their
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recognition and elimination by the
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immune system these strategies involve
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latency reversing agents laras such as
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protein KES C histone DS
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histone dylus Inhibitors and toll like
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agonists toll like receptors tlr a
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family of pattern recognition receptors
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play a critical role in recognizing HIV
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one molecular structures by various
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cells of the innate immune system they
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also provide a functional association
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with subsequent adaptive immune
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mechanisms tlr7 and tlr8 are
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particularly important in the innate
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immune response to RNA viruses as they
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can recognize guur single stranded RNA
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molecules and subsequently activate
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intracellular signaling Pathways
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resulting in the expression of genes
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coating for various biological response
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modifiers such as interference
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pro-inflammatory cyto kindes and
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chemokines sengupta recently reported
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results from a randomized double blind
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Placebo controlled phase Oni clinical
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trial on an lt7 Agonist Vitaly mod in
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successfully treated HIV V infected
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persons an oral too7 Agonist induced
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immune activation of DCs and NK cells
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leading to a decreased quantity of
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intact proviral DNA in the patients
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lower quantities of intact proviral DNA
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13 days after the final dose of the tlr
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7 Agonist also predicted a delayed viral
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Rebound in the patients these results
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showed that tlr7 agonists might
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represent an option in treatment
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regimens aimed at long-term control of
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HIV one the most recent study by Riddler
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at Al 2022 reported results on the use
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of atlr 7 Agonist in a double blind
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multicenter Placebo controlled clinical
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trial that included 36 successfully
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treated patients with undetectable
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plasma Vira these results showed that
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tlr s agonists represent a promising
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candidate drug aimed at achieving immune
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stimulation in future clinical trials
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assessing the Effy of HIV candidate
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the future of tlr agonists in clinical
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trials involving therapeutic vaccination
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and in Research into the development of
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a functional cure for hiv1 infection
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looks promising with several studies
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that are currently recruiting patients
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or have been announced currently there
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are two clinical trials that will
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evaluate the role of tlr7 and tlr9
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agonists combined with bonab agonists
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combined with bonobas potential tools to
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achieve long-term virological control in
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HIV in infected patients an
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Interventional Gilead phase to a
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5,281 510 will evaluate a sequential
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regimen of HIV andv specific monoclonal
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antibodies vrcs 7 523 LS and capap 256
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vono the trial will include 25 women
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infected with HIV subtype C that started
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anti- retroviral therapy at the acute
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stage of infection the trial will
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monitor time to virological rebound viia
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at the end of analytical treatment
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Interruption ATI as well as the time to
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resumption this trial is specifically
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designed to address the issue of HIV one
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subtype C infection in women the focus
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on women is particularly important due
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to a well-established fact that gender
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inequality and harmful gender Norms
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restrict women's access to Healthcare
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Services related and non-related to HIV
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and results in a disproportional risk
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infection according to the unad
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epidemiological estimates there were
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150,000 390,000 new HIV infections
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globally among adolescent girls and
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young women with 83 of these infections
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occurring in subsaharan Africa were
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adolescent girls and young women at edin
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24 years account for 25 of Nick
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infections despite representing only 10
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population therefore clinical trials
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addressing specific vulnerable groups
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such as women infected with subtype C
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are of outmost importance in hive
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medicine also the University of aus has
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announced a phase 2 investigator
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initiated randomized Placebo controlled
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clinical trial evaluating the effect of
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The tlr9 Agonist lafido modee in
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combination with broadly neutralizing
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EnV specific anti-v EnV specific anti-v
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117 1074 in height individuals on Art
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and during ATI as an intervention to
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Reservoir the study is designed to
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enroll 47 HIV infected adults aged 1865
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years that have been treated with
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anti-retroviral drugs for a minimum of
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18 months and had undetectable Veria as
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well as 400 cd4t cells at enrollment the
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study will evaluate the sensitiv ity of
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the viral Reservoir to neutralization
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using a standardized phenosense HIV mab
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assay or HIV 1 DNA envelope sequencing
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in combination with an appropriate
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algorithm the aim of this video is to
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summarize the current knowledge on the
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role of tlr in recognizing HIV one
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molecular patterns and activating innate
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immune responses to the virus in our
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subsequent videos we'll explore the role
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of tlr agonists in current and and
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future clinical trials aimed at
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developing HIV one vaccines and novel
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therapeutic strategies for a potential
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cure and that is it in today's video
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thank you for joining us on this
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informative Journey Don't forget to like
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