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Slide1
Inégalités en santé et VIH
Tous égaux ? Et les virus…Grenoble; 01 Octobre 2021; JC Tardy
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Slide3Interaction of the
Host and Viral Genome and Their Influence on HIV Disease
Host genomics of HIV infection hasbeen studied predominantly in Caucasian populations consistently identifying human leukocyte antigen (HLA) genes and C-C motif chemokine receptor 5 as key factors of HIV susceptibility
and progression
R.H Tough et al ; Front.Genet. 2019
It has been clearly demonstrated that both
host and viral genetics
play a vital role in determining HIV acquisition and disease progression Current evidence supports the role that viral subtype has an effect on disease progression, however, there is also evidence against this claim
Slide4Are All HIV Type 1 Strains Created
Equal?T.P Campbell ; JID 2005
Slide5M.Giovanetti
et al ;
Pathogens 2020
Gag Pol
Env
Gag Pol
Env
November 2020 :
106 CRFs have been registered by the Los Alamos2010-15 : subtype C is responsible for 46.6% of infections, B for 12.1%,A for 10.3%, G for 4.6%,D for 2.7%CRF02-AG for 7.7%, CRF01-AE for 5.3%
VIRAL SEX The nature of AIDSJaap Goudsmit 1997
Slide6B is the most prevalent in the Americas, Europe
C in Southern Africa and India, A in the Soviet Union and parts of East Africa, CRF01_AE in Asia, CRF02_AG in Western and Central Africa
J.Hemelaar
et al ; Lancet
Inf.Dis. 2019
Slide7Does Genetic Diversity of HIV-1 Non-B Subtypes Differentially Impact
Disease Progression in Treatment-Naive HIV-1–Infected Individuals? A Systematic Review of Evidence: 1996–2010
N.Pant Pai
et al ; J.AIDS 2012
Subtypes C and D were more aggressive, followed by G, AE, and AG, and A being the least aggressive of all HIV-1 subtypesInfecting HIV-1 Subtype Predicts
Disease Progression
in Women of
Sub-Saharan AfricaC.M Venner et al ; EBioMedicine 2016HIV-1 subtype C was less virulent than either A or D in humans; longer periods of asymptomatic HIV-1 subtype C could explain the dominance of subtype C
Understanding the mechanisms driving the spread of subtype C HIV-1M.J Gartner et al ;
EBioMedicine 2020Does subtype C HIV-1 have a replication advantage?Subtype C undergo coreceptorswitching less frequently than other subtypesStudies of T/F viruses do not suggestC-HIV is more fit for transmission than other subtypesThe rapid expansion of C-HIV was not a result of viral evolutionary factors but could be the result of the introduction into high-risk populations during a time of complex socio-political changes
Slide8HIV-1 subtypes and
differences in heterosexual HIV transmission among HIV-discordant couples in Rakai, UgandaSubtype A viruses have a significantly higher rate of heterosexual transmission than subtype D viruses
N.Kiwanuka et al ; AIDS 2009
HIV-1 Tropism and Survival in
Vertically
Infected
Ugandan
Infants
J.D Church et al ; JID 2008Does HIV-1 Subtype D
Have a Higher Risk of Vertical Transmission than Other HIV Subtypes?
…we propose that pregnant women infected with HIV-1 subtype D should be considered as having a high
risk of vertical transmission
A.Krivine et al ; JID 2009
Slide9Effets of HIV‑1
genotype on baseline CD4+ cell count and mortality before and after
antiretroviral therapyZ.Cao et al ;
Scient.Rep
. 2020In the ‘after ART’ cohort, our analyses revealed no significant difference
in mortality among HIV patients with
different
genotypesIn the ART-naïve cohort, there were significant associations between HIV patients with CRF01_AE and lower baseline CD4+ cell count at diagnosis, as well as higher mortality, compared with CRF07_BC, CRF08_BC, and other genotypes… comparisons of virulence and transmissibility are hampered by potential confounders, such as ethnic, socioeconomic, and other
epidemiological factorsHIV-1 Genetic Variability and Clinical ImplicationsM.M Santoro et al; ISRN Microbiol. 2013
Slide10A.J Mc Mickael et al ;
Nat.Immunol
. 2012
Global and Regional Estimates for
Subtype-Specific
Therapeutic
and Prophylactic HIV-1 Vaccines: A
Modeling Study
R.Elangovan et al : Front.Microbiol. 2021Genetic divergence between HIV-1 subtypes is substantial, with Env displaying a median difference of 25%The large
genetic divergence between HIV-1 subtypes makes it difficult to elicit immune responses that are sufficiently cross-reactive between HIV-1 subtypesWe modeled different scenarios according to whethercountries would employ subtype-specific HIV-1 vaccines against (1) the most common subtype; (2) subtypes contributing more than 5% of HIV infections; or (3) all circulating subtypesIf all 10–49-year-old people would be vaccinated against the most common subtype circulating in each country, an estimated 4.1 billion doses of vaccines would be required globally, of which 1.9 billion were subtype A, 1.1 billion subtype C, and 1.0 billion subtype B
Slide11For all HIV-1
vaccine approaches, it is crucial to have up-to-date knowledge of
HIV-1 genetic diversity to allow prioritization and development of vaccine concepts that are likely to provide the greatest benefitto specific countries, regions, and the world
R.Elangovan
et al :
Front.Microbiol
. 2021
Slide12SEROLOGICAL EVIDENCE FOR
VIRUS RELATED TO SIMIAN T-LYMPHOTROPIC RETROVIRUS III IN RESIDENTS OF WEST AFRICAF.Barin et al ; Lancet 1985
These results suggest that certain healthySenegalese people have been exposed to a virus that is more closely related to STLV-III than to HTLV-III. The existence and study of such virus variants potentially with differential pathogenicity…
Isolation of a
New Human Retrovirus from West African Patients with AIDS
F.Clavel
et al ; Science 1986
We report here the isolation, from these two patients, of a new human retrovirus that is related to but distinct from both LAV/HTLV-IIIHIV-2 is generally less pathogenic than HIV-1; HIV-2 infection typically involves a longer asymptomatic stage,slower decline in CD4 count, lower mortality from AIDS, lower mother-to-child transmission, and less genitalshedding and sexual transmission than HIV-1
Slide13En cas de résultat positif, une analyse de
confirmation par western blot ou immunoblot est réalisée à l’initiative du biologiste médical sur le même échantillon sanguin et permet de
différencier une infection à VIH 1 ou à VIH
2
Extraits de l’arrêté du 28 mai 2010
Y.T Lai et al ;
Viruses
2021
Chaines latérales plusvolumineuses présentes sur des acides amines tels que le tryptophane (mutation S375W) ou l’histidine (mutation S375H) empêchent probablement l’entrée et/ou la liaison du temsavir qui n’inhibe pas l’entree du VIH-2, qui a un résidu W a la position 375
HIV-2 OK NRTI, PI, INSTI HIV-2 : Naturally resistant to : all NNRTI ENFUVIRTIDEFOSTEMSAVIRV.H Wu et al ; AAC 2017MK-8591 is highly active against a broad range of
HIV-2 isolates from ART-naive individuals
Slide14G.S Gottlieb et al ; Lancet HIV 2018
90-90-90 for HIV-2? Ending the HIV-2 epidemic by enhancing care and clinical management of patients infected with HIV-2Globally, the status of UNAIDS/WHO 90-90-90 targets for HIV-2 infection is
unknown because of the scarcity ofrobust data and accurate metrics. For the first 90 target (90% of all people living with HIV-2 will know theirHIV-2 status), data regarding both the numerator (ie, the number of individuals infected with HIV-2 whoknow their status) and the denominator (
ie, countrywide
HIV-2 prevalence) are absentRough estimates on the
second and third 90 targets
can be extrapolated with
caution in west AfricaA study from the network found that 54% of 1021 adults with HIV-2 were on ART, and a second study estimated that 58% of 351 adults with HIV-2 were virally suppressed on ART or had naturally undetectable viral loadThese sparse data suggest that much work
needs to be done to first assess and ultimately achieve 90-90-90 for HIV-2
Slide15Surveillance of HIV-1
primary infections in France from 2014 to 2016:toward stable resistance, but higher diversity, clustering
and virulence ?
B.Visseaux
et al ; JAC 2020
Since 2007, the proportion of
TDRAMs
has been stable among French PHI patients. Non-B lineagesare increasing and may be associated with more virulent CRF02_AG strains
Regarding HIV diversity, subtype B and CRF02_AG were the two main lineages (56% and 20%, respectively)
Slide16A
(2163)
B(10295)C
(4427)D
(701)F(352)G(273)AE(2405)
AG
(1334)
L74I (%)373,86,34,03,4122,516L74M (%)1,3
3,01,03,36,2
Stanford HIV db 9.0
D64 L74
T97
D116 E152 E157
Positions conservées (D64,D116,E152)
Positions polymorphes (L74, T97, E157)
L74I
T97A
E157Q
Slide17Zhang JID 2018;
K.Anstett
JAC 2016)
NL4.3:
1
E157Q :
0,01
R263K :
2
E157Q R263K :
19,9
T97A
Q148H
G140S
E157Q
R263K
L74I/M
DTG FC
BIC FC
CAB FC
345
67
586
28
9
74
3,02,53,7
FC DTG
bictegravir
(BIC)
Susceptible
cabotegravir
(CAB)
Susceptible
dolutegravir (DTG)
Susceptible
Slide18Fernandez C et al; HIV AIDS (
Auckl). 2019
Jul 31
Genetic Features of HIV-1 Integrase
Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to
INSTIs
Additionally, we confirmed that the
L74I mutation was selected at the early stage of the epidemic and subsequently spread as a founder effect in Russia
A.Kirichenko et al ; Viruses 2020HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia
M.Schlosser et al ; Viruses 2020Online genotyping and subsequent phylogenetic analysis showed that the most frequent clade was
sub-subtype A6 (350 sequences; 85.8%)
Slide19Prevalence of genotypic baseline risk factors for
Cabotegravir+rilpivirine failure among ARV-naive patients
C.Charpentier
et al ; JAC 2021
Among 4212 ARV-naive patients, 38.6% were infected with subtype B, 32.4% with CRF02_AG (32.4%)
and 5.1% with subtype A (85.5% being A6/A1 subtype)
The overall prevalence of L74I in integrase and E138A in RT was 13.0% and 3.2%, respectively, and stable over the decade
Among large sequence databases, when adding prevalence of
rilpivirine
-resistant viruses and HIV-
1 subtype A6/A1 sequences, 10.1% of patients would not be eligible for cabotegravir!rilpivirine dual therapyConsidering genotypic resistance interpretation, using the ANRS
algorithm
Slide20Gut Microbiome
Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients
W.M do
Nascimento
et al ;
Viruses
2020
Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such asSuccinivibrio, which were more abundant in patients infected by HIV subtype B, and Streptococcusenrichment in patients infected by subtype C
Slide21Patrick
O'Connell
(1953-2021) Visual AIDS