Hôpital Bichat Claude Bernard - Paris and the French National HIV-2 Cohort
HIV-2 : 6 subtypes designated A to F •
2 major HIV-2 subtypes : A and B A endemic in West Africa B mainly in Côte d’Ivoire and Mali Inter-subtype A and B recombinants
•
4 minor HIV-2 subtypes : C to F Liberia and Sierra-Leone, highly divergent from subtypes A and B (>25% Gag and Env)
HIV-2 genetic diversity in France Objectives : - to study the prevalence of HIV-2 subtypes in France - to study the clinical and biological consequences of this diversity - to investigate the relation between HIV-2 diversity and serological reactivity
Patients and Methods 40 HIV-2-infected patients living in France : - 39 from the French ‘HIV-2 prospective cohort’ - 1 patient falsely negative by a third-generation EIA
-DNA extracted from fresh uncultured lymphocytes - Integrase-LTR XL PCR - followed by env nested PCR using different set of prime LTR
Integrase
ENV
POL EB0
EB2
EB4
EB6
EB7
EB5 Env A
Env C Env E
Env F Env D Env B Env G
V3 LOOP
TM
DNA- HIV-2 amplification - 40 patients Age 41 ± 11 19 M and 17 F CD4+ = 304 ± 239/ml - 36 strains PCR-positive between C2-V3 and gp 41 were sequenced.
- 4 patients with CD4 > 500 : amplification failed
HIV-2 diversity in France HIV-2 subtype Patients’ origin Bissau Burkina-Faso Cape-Verde Congo Côte d’Ivoire France Ghana Mali Morocco Martinique Poland Senegal
. . . KN. . AA. EQ. . QM. K. . I . . V. . . N. . . . L. . . . E. . . . . . I . . . . WK. . . .
SIVmnd
. . K. - . . KLI EQ. S. L. K. . I . . V. . . . T. L. SL. N. I K. . . L. SQ. . . SWA. . . . V. . . N. . RAI EA. . HL. Q. . . . . I . Q. . . . . L. V. R. . K. . L. GI . . . SGKKI . -
HIV-2 sensitivity to antiretroviral drugs in vitro
nevirapine S
indinavir 9
ritonavir 4
saquinavir 9
A R
9
5
subtype S
6
3
6
1
4
1
B R
7
Phenotyic susceptibility of 9 subtype A and 7 subtype B strains IC50 determination R : IC50 at least 4 times higher than HIV-1 subtype B IC50
HIV-2 genetic diversity in France Conclusions
•Both subtypes A and B are cocirculating in France •Both subtypes A and B are pathogenic in vivo •HIV-2 subtype B has been present in Côte d’Ivoire since at least 1982 •One sample corresponding to a ‘distant’ subtype B was falsely negative by a third-generation HIV-1/2 screening EIA
HIV-2 genetic diversity in France Conclusions
• subtypes A et B have a phylogenic double-star configuration • Phylogenetic positions correlated with the geographical origin of the strains, in accordance with phenetic analysis (B.Korber)
• Sera from subtype B-infected patients are strongly cross-reactive on the HIV-1 immunodominant domain, even by Western-Blot
• HIV-1/HIV-2 dual reactivity in West-African patients could be explained at least in part by HIV-2 subtype B infection
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