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Characterization of HIV Drug Resistance in Malian Cohort in West Africa Mali

Characterization of HIV Drug Resistance in Malian Cohort in West Africa Mali. Maiga AI , Diallo F, Fofana DB, Maiga IA, Cissé M, Daou F, Traore HA, Maiga MY, Dao S, Minta DK, Sylla A, Murphy R, Tounkara A, Katlama C, Calvez V, Marcelin AG. Laboratory in Gabriel Teaching Hospital

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Characterization of HIV Drug Resistance in Malian Cohort in West Africa Mali

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  1. Characterization of HIV Drug Resistance in MalianCohort in West Africa Mali Maiga AI, Diallo F, Fofana DB, Maiga IA, Cissé M, Daou F, Traore HA, Maiga MY, Dao S, Minta DK, Sylla A, Murphy R, Tounkara A, Katlama C, Calvez V, Marcelin AG Laboratory in Gabriel Teaching Hospital Molecular and Epidemiology of HIV Drug Resistance – SEREFO University of Bamako Bamako - MALI

  2. République du Mali Un peuple - Un but - Une foi Prevalence (VIH1 et VIH2)in des différentes régions Prévalence en 2001 1,7% EDS III 14 millions people 1 241 238 km2 182 000 personnes infectés par le VIH

  3. Scaling up ART Mali Dec 2010: 33 500

  4. Early First Line failure of Triomune in Mali Possibility to use the others NRTIs for second line treatment Marcelin et al, AIDS 2007

  5. Late First line failure in Mali and Burkina Faso 40% of TAMs, the others NRTIs use is not possible most of theses patients Sylla and al, Antivir Ther 2008

  6. Hosseinipour MC, AIDS 2009

  7. Objectives • To determine the prevalence of drug resistance mutations among patients failing to second-line ART • To characterize the resistance genetic profiles • To evaluate the susceptibility to ARVs and especially those that can be used as part as third line therapy in RLS.

  8. Methods • 2nd line HIV-1 infected patient were selected with • VL > 1000 copies/mL recently done • Received 3 classes of ARVs avalaible in Mali • Sequencing and sequence analysis was done with the method VIROSEQ • Resistance mutation interpretation was performed with the Stanford algorithm.

  9. RESULTS

  10. Characteristics of study population with sequences (n=93) • Age, year median (IQR) 35 (24 -46) • Females, % 67% • Viral load, copies/ml median (IQR) 72 000 • HIV-RNA copies/ml% • < 1000 3% • 1000 – 5000 12% • > 5000 74% • CD4 count, cells/µl median (IQR) 146 (19 -273) • HIV Subtype 02_AG % 67%

  11. Previous exposure to antiretrovirals • Number of drug exposure, median (IQR) including current treatment • ARVs 6 (5 - 7) • NRTIs 4 (3 - 5) • NNRTIs 1 (0 - 1) • PIs 1 (0 - 1) • Duration of prior antiretroviral therapy, year median (IQR) • NRTIs 4 (2 - 6) • NNRTIs 2 (1 - 3) • PIs 2 (0 – 4) • ARVs 4 (2 - 6)

  12. Drugs to which the patients wereexposed % Antiretroviral Drugs

  13. Prevalence of IAS NRTI Mutations % IAS NRTI Mutations

  14. Prevalence of IAS NNRTI Mutations Minor Major % IAS NNRTI Mutations

  15. Prevalence of IAS PI resistance mutations Minor Major % IAS PI Mutations

  16. Prevalence of resistance to each drug according to Stanford algorithm % Antiretroviral Drugs

  17. Resistance or possible resistance to all ARV in one family % Antiretroviral Families (8/93) 8,6% des virus sont résistants à tous les ARV des 3 familles

  18. Factors associated to resistance of drug which can be use in second line • PIs time exposure is associated to the resistance to : • LPV/r p< 0,0001 • DRV/r p= 0,006 • NRTIs time exposure is associated to the resistance to : • ABC p< 0,0001 • TDF p= 0,0001 • NNRTIs time exposure is associated to the resistance to • ETR p< 0,0001

  19. Factors associated to resistance of drug which can be use in second line • DRV resistance is associated to : • Pis time exposure (p = 0.006) • VL level at failure (p = 0.007) • LPV exposure (p = 0.045) • The presence of L76V mutation (p = 0.0001) • In multivaried analyze: only the VL at failure and the L76V mutation

  20. Conclusions • Exposure time to ARVs is associated to the resistance (ETR 38%, DRV 12%) • Need of viral load testing to detect the early virological failure • Change the treatment at failure, not lately • Need of resistance testing for 3rd line initiation for best use of new drug (ETR+++) • 8% of multiresistant viruses • What is the therapeutic option?

  21. HIV Resistance Team at University Djeneba FOFANA, Almoustapha MAIGA Anatole TOUNKARA

  22. Thank! Malians Actor for HIV/AIDS Pitié-Salpêtrière France Anne-Geneviève MARCELIN Zaina AIT-ARKOUB Roland TUBIANA Guislaine CARCELAIN Christine KATLAMA Vincent CALVEZ Anatole Tounkara Almoustapha MAIGA Djeneba Fofana, Fatoumata DAOU Aboubacar A OUMAR Aicha Chehy MAIGA Aliou BALDE Equipe SEREFO Hamar A TRAORE, Mamadou DEMBELE, Daouda MINTA, Ibrahim I MAIGA Sounkalo DAO Moussa MAIGA Mohamed HAIDARA, Yaya BALLAIRA, Aboubacrine MAIGA Mariam SYLLA Anta SISSOKO Hadizatou COULIBALY Clementine N’Diaye Mamadou CISSE Fodié DIALLO Tiefing KONATE Naye BAH Brehima SANGARE Aboubacre TEKETE Etienne ALGIMAN Issouf MAIGA Dionké FOFANA Pierre MENDIARAT Gilles BRUCKER Gilles RAGUIN Northwester University Chicago Robert MURPHY Babafemi TAIWO National AIDS Program – Mali Aliou SYLLA Aminata TRAORE Fatoumata MAIGA Abdoulkarim BERTHE

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