Inégalités en santé et VIH - PowerPoint Presentation

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Inégalités en santé et VIH

Tous égaux ? Et les virus…Grenoble; 01 Octobre 2021; JC Tardy

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Liens d’intérêts

Interaction 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

Are All HIV Type 1 Strains Created

Equal?T.P Campbell ; JID 2005

M.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

B 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

Does 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

HIV-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

Effets 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

A.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

For 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

SEROLOGICAL 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

En 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

G.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

Surveillance 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)

A

(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

Zhang 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

Fernandez 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%)

Prevalence 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

Gut 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

Patrick

O'Connell

(1953-2021) Visual AIDS