Clinical case of transmitted resistance to HIV Integrase...
Transcript of Clinical case of transmitted resistance to HIV Integrase...
Clinical case of transmitted resistance to HIV Integrase
Inhibitors
González-Domenech CM1, Viciana I1,2, Jarilla F3, Palacios R1,2,
Roldán J3, Santos J1,2
1Biomedical Research Institute of Malaga (IBIMA), Málaga, Spain; 2Infectious Diseases and Clinical
Microbiology Unit, Virgen de la Victoria Hospital, Málaga, Spain; 3Service of Internal Medicine,
Antequera Local Hospital, Málaga, Spain
2nd Global HIV Clinical Forum on Integrase Inhibitors. 22nd July, 2017. Paris (France)
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Background
Recommendations about resistance of HIV-1 to antiretroviral drugs
Assessment of baseline integrase resistance mutations is only recommended when there is a highsuspicion of transmission of resistance to integrase strand transfer inhibitors (INSTI).Multiple resistance in PR and/or RT or index patient treated with INSTI
Resistance should be studied by genotyping in all patients in whom virological failure has beenconfirmed. The study should include integrase resistance mutations if the patient's regimenincludes an INSTI
The Spanish Aids Research Network (RIS) study during period
2007-2012 Overall prevalence for protease and reverse
transcriptase resistances ~7.6%; rare integrase resistances
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Objective
To report a clinical case of INSTI resistance evident transmission from a long
treatment experienced HIV patient to his partner
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Patients and methods
Partner infection timeline
Initial
resistance
test
Genotypic tests & phylogenetic analysis
Phylogeny
of transmitted
HIV-1 strain
2004 2016 Present
Viral load evolution
Medical & treatment history of primary case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
• Male (58 yrs)
• HIV-1 diagnosed in 2004
• HCV coinfected, genotype 1a
• Severe hypertension, associated
with cerebrovascular, kidney and
myocardial disease
Index case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Clinical follow-up
3TC + ddI + d4T Discontinuation
(CD4 count=123 cells/µL;
Viral Load=24,600 copies/mL)
AZT + ABC + EFV Viral suppression
HCV treatment beginning
3TC + ABC + EFV Virological failure
Index case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Clinical follow-up (cont.)
AZT + d4T + ATV/r
Virological failure
(HIV-1 VL=2,860 copies/mL)
GENOTYPE RESISTANCE TEST
74V, 184V, 100I, 103N
ABC, ddI, 3TC, NVP & EFV
Viral suppression
Index case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Clinical follow-up (cont.)
AZT + d4T + RAL
Occasional blips
Virological failure
Viral suppressionFrom 2008:
HCV treatment beginning
with Harvoni®
HCV cureGENOTYPE RESISTANCE
TEST
SVR
Index case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Clinical follow-up (cont.)
Virological failure
(HIV-1 VL=9,627 copies/mL)
GENOTYPE RESISTANCE TEST
98S (RT mutation)
G140S, Q148H (integrase mutations)
DRV/r + d4T + AZT
Rescue therapy
Index case
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Partner of index case
• Female (52 yrs)
• HIV-1 diagnosis in May of 2016
• Baseline genotype resistance test
performed
- Initial CD4 count=476 cells/µL
- Initial Viral Load=48,412 copies/mL
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
98S (RT mutation)
G140S, Q148H (integrase mutations)
Baseline genotype resistance test
Partner of index case
Index case
Idem mutations pattern
Viral suppressionCD4=630 cells/µL
FTC + TDF+ RPV
Initial antiretroviral therapy
VL=142 copies/mLCD4=426 cells/µL
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
Phylogenetic relationship index case and partner
Identity
pol gene (PR+RT+IN) from index case in VF and his wife (naïve)
VF= Virological failure
pol gene 98.93%
IN region 98.95%
Aminoacids identity
96.83%
97.91%
Divergence
Integrase
PR+RT+IN
0.005%
0.011%
Protein divergence
Integrase
PR+RT+IN
pol gene 0.008%
IN region 0.004%
DNAstarsuite
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Results
VF= Virological failure
PR+RT+IN from the 2 patients(index case in VF and his wife)
pol gene from 150 patients epidemiologicallynon-related and randomly retrieved fromLANL database
Determination of nucleotidic sustitution model(in that case GTR+G+I, by Findmodel, MEGAv6.0)
Phylogenetic inference by ML (FastTreeprogram)
ML= Maximum Likelihood
Phylogenetic relationship index case and partner
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Phylogenetic relationship index case and partner FastTree
2004
B U
S.9
9.P
RB
959
03.A
Y33
1296
2004 B GB.x.MANC.U23487
90
0.01
99%
Phylogenetic relationship with HIV epidemic
Clinical case of transmitted resistance to HIV Integrase Inhibitors2nd Global HIV Clinical Forum
Conclusions
Both cases reported are epidemiological and phylogenetically related to eachother, also sharing the same integrase mutation pattern
Both strains are highly similar to each other and phylogenetic study confirms theirevolutive closeness
In summary, we can conclude the transmission of a HIV-1 strain showing InSTI
resistance mutations from the index case to his common partner.
Thanks for your attention!