Le VIH en 2014

Filip Moerman
Infectiologie CHR C Liège
Le 18 mars 2014
HIV-2 reservoir: Sooty mangabey (Cercocebus atys)
HIV-1 reservoir: Chimpanzee (Pan troglodytes troglodytes)
HIV-N (new)
HIV-O (outlier) <1%
HIV-M (main)
<1%
>98%
Subtype A: 23%
Subtype B: 8%
Subtype C: 56%
Subtype D: 5%
Subtype E: 5%
Subtypes F-K: 3%
I
HIV-1 (N)
J
HIV uses CD4 to attach to T cells
17
Acute retroviral
Toxoplasmosis
syndrome
KS Oral hairy leuco PCP
Cryptoccocosi
Vaginal
plakia
s
candidaRecurrent
Oes
Pneumonia
500
candida
Pulm TB
HZV Thrush
200
50
Spectrum of OI,s
CMV
MAI
24/03/2014



Increases survival
Increases quality of life
Decreases mother-to-child
transmission of HIV
Medical
services
Nursing
Care
People living
with HIV/AIDS
Social
support
Counselling
30000
25000
Number of AIDS cases
HAART
20000
15000
10000
5000
19
86
19
87
19
88
19
89
19
90
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
0
European Centre for the Epidemiological Monitoring of AIDS, France, 2001
Le traitement antirétroviral en résumé..
Traitement des infections opportunistes
Prophylaxie des infections opportunistes
Traitement antirétroviral
“HAART”
Immunothérapie
1980
1990
*En Europe & Amérique du Nord
2000
Futur
Available antiretroviral medication over time
ENF
ATV
FTC
FPV
Number of Approved Agents
25
20
TDF
EFV
ABC
15
LPV/r
APV
NFV
RTV DLV
IDV
NVP
10
5
ddC
ddI
3TC
SQV
d4T
AZT
0
1987
1989
1991
1993
1995
1997
1999
2001
2003
Available antiretroviral medication 2006
NRTI
NNRTI
PI
Fusion inhibitor
3TC
nevirapine
ritonavir
AZT
efavirenz
nelfinavir
ABC
delavirdine
saquinavir
enfuvirtide
ddI
amprenavir
d4T
fosamprenavir
ddC
indinavir
FTC
atazanavir
TDF
lopinavir
tipranavir
NRTIs (nucleoside analogues)
 Nucleotide analogues
 NNRTIs (non-nucleoside analogues)
 PIs (protease inhibitors)
 Fusion / Entry inhibitors
 [CCR5 - en CXCR4 inhibitors (blockers) =
co-receptor entry inhibitors.]
 [Integrase inhibitors]

NRTIs (nucleoside analogues)
 Nucleotide analogues
 NNRTIs (non-nucleoside analogues)
 PIs (protease inhibitors) – two generations (!)
 Fusion inhibitors (+/- no longer used)
 CCR5 (CAVE CXCR4) inhibitors (blockers) = coreceptor entry inhibitors. Determine Tropism!
 Attachment inhibitors (very recent) (attachment – Co
receptor CCR5 – fusion)
Integrase inhibitors (!)
 Maturation inhibitors (very recent) (just before exocytosis;

inhibition of the final step in the processing of HIV-1-gag-protein, just after PI)
Entry
RNA
Viral protease
RNA
Proteins
Reverse
transcriptase
RT
RNA
RNA
DNA
RT
DNA
DNA
Provirus
Integrase
CD4
Binding
Coreceptor
Binding
Virus-Cell
Fusion
Enfuvirtide
gp41
gp120
V3 loop
CD4
CCR5/CXCR4
Cell membrane
The same AND
 Int Inh: Raltegravir, Dolutegravir, Elvitegravir
(Isentress, Tivicay, Stribild (!)/Cobicistat-RTV);
Dolutegravir + ABC/3TC = Trii
 PI’s: Darunavir (TMC-114 = Prezista)
 CCR5-inh: Maraviroc (celsentri), Cenicriviroc
 NNUC: Rilpivirine (Edurant – Eviplera),
Etravirine (Intelence)

Clinical Category
CD4+ Cell
Count
Plasma
HIV-1 RNA
General Guidelines
AIDS-defining
illness
or severe
symptoms*
Any value
Any value
Treat
Asymptomatic
< 200
Any value
Treat
Asymptomatic
200-350
Any value
Treatment should be offered
following full discussion of
pros and cons of treatment.
Asymptomatic
> 350
≥ 100,000
Most clinicians recommend
deferring therapy, but some
clinicians will treat.
Asymptomatic
350
Defer
therapyweight loss.
* Severe symptoms = unexplained>fever
or diarrhea<> 100,000
2-4 wks, oral candidiasis, or >
10% unexplained
DHHS guidelines. http://AIDSinfo.nih.gov. Accessed November 11, 2004.


In essence no change, i.e. CD4+ T-cell count based:
between 200-350/µl (Andrew Philips AIDS 2003) OR ‘AIDS def illness
BUT: in case of persistent high or moderate viral load,
even in case CD4 count remains relatively stable and
above 350, tendency to start! Deeks Steven BMJ 2006. Differs
from Mussini’s view:

“What role does the viral load still play?” Mussini C. AIDS
2006.

Seroconversion: no evidence yet to start, although…
Streeck et al JID 2006

STI further controversial Bongiovanni et al. J Antimicrob Chemother
2006
In general the threshold has come (reimbursement) to 500 CD4, OR
 OI / Clinical AIDS-definition, OR
 Pregnancy
 Consider if pt in Seroconversion (and
ready!), lives with partner and has high viral
load
 For every HIV-1+ person in the future…? (not

re-imb if > 500 CD4)
Lipodystrofie
Stevens-Johnson Sy
No HBV/HCV
No Primary Resistance
No Superinfection
Excellent Compliance
•Choice of therapy in HIV + Hep B
coinfection:
•If HAART indicated:
•include 3TC/FTC and/or TDF in HAART
•for hepB treatment
•or at least to prevent hepB immune reaction
•If HAART not indicated:
•3TC/FTC/TDF not recommended
•PEG-IF, ADF, …? Use non HIV guidelines
•Considerations in HIV + Hep C coinfection:
•ddI contraindicated with ribavirine therapy
Care and prevention
should always go
hand in hand.
Condom rules have
changed: Swiss
guidelines
Condoms
Révéler le diagnostic, le stigmatisme
 Prendre un traitement pour la vie
 Commencer une vie familiale
 Et mes parents docteur….?
 Et mon travail docteur…?
 Et acheter une maison docteur…?


Beaucoup de problèmes sexuelle…: « sexual
dysfunction is underestimated! »
Ora quick: oral HIV Ab test
 This cheek swab has been promoted in Toronto
 Reflections on its use should carefully include:

 Use
by paranoid people
 False Positives
 Window period
 Stigma
 Evaluation
 Is HIV testing to be done exclusively in a Health
Care setting? YES.


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In hiv+gay men: preval rate of HSV-1: 75% and HSV2: 23%.
In the general Dutch population seroprevalence of
HSV-1 is 59,5% and 8.4% for HSV-2.
In Africa: HSV-1 & 2- preval=40% in male
Zimbabweans Mc Farland et al. JID 1999..
90% is unaware of their HSV-2 inf Wald et al. JID 2006.
New transmission patterns of HSV Kim N et al; JID 2006.

Circumcision could prevent many infections Kühn et al. JAMA 2006;
Auvert et al. PLoS Med 2005. Mechanism doubtful (Langerhanscell?).
Implications for future research.

Microbicides: phase III results , Incl TFV, TMC-120: doubtful
(prostitutes to be protected by female condom use)

PrEP = PRE-exposure prophylaxis: the currently available
information has become sufficient to recommend PrEP use “in
theory”
Survival
 Morbidity ↑ (bone, liver, kidney, neo)
 Cardiovascular disease: Glass, et al HIV Med 2011+.
 Vaccine, preventive; Vaccine, therapeutic; Cure
 Confrontation with features of a ‘CHRONIC
DISEASE’: treatment fatigue, depression, MD
approach, disclosure again and again,...
 Treatment as soon as diagnosed: reduction of
Incidence, but what about the “don’t knows”?
Different arguments pro/contra.
 Dolutegra-deriv chez SIV-macaques: 3 mois
actif! Potentiellement: Rilpi (IM poss) +
Dolutegra-deriv IM

Environ 40 millions personnes touchées
(PLUS 1/3 à ¼ ne le sait pas encore)
 Le fardeau encore plus grand en Afrique
 Là: 50% est sur HAART (seuil pas à 500
CD4)
 Par jour encore 4400 morts…..
 Per ex: RSA: 750 morts par jour!
