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MOAB0104

Reinforcement of adherence and switch to third-line in HIV-infected adults who fail second-line ART Thilao study (ANRS 12269), West Africa. MOAB0104.

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MOAB0104

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  1. Reinforcement of adherence and switch to third-line in HIV-infected adults who fail second-line ARTThilao study (ANRS 12269), West Africa MOAB0104 Raoul Moh, A. Benalycherif, D. Gabillard, ML. Chaix, C. Danel, L.Slama, C. Michon, PM. Girard, C. Toure-Kane, T. Toni, E. Bissagnéné, J. Drabo, M. Seydi, D. Minta, A. Sawadogo, X. Anglaret, S. Eholié, R. Landman 1 ANRS research site in Côte d’Ivoire

  2. Conflict of Interest “No conflicts of interest to declare”. 2

  3. Background In sub-Saharan Africa: • ART regimen sequencing is based on WHO guidelines: • NNRTI-based (1st line), PI (LPVr or ATVr)-based (2nd line), DRVr + INSTI-based (3rd line). • Increasing access to: • Second-line antiretroviral drugs • Viral load testing • Very low access to: • Third-line antiretroviral drugs • Genotypic resistance testing  Need for strategies that help physicians to decide when to stwich to third-line ART • « Not too early » (unjustified switch, patients with high GSS) • « Not too late » (risk of resistance accumulation) 3

  4. Thilao ANRS 12269 : Methods • Design: Pilot study. First inclusion: March 2013. Last visit: Aug 2016 • Settings: Burkina-Faso, Côte d’Ivoire, Mali, Senegal • Inclusion criteria: • Adults >18 years • History of: • 1st-line NNRTI-based regimen • Switch to 2nd-line PI-based ART for virological failure • More than 6 months on 2nd-line PI-based ART (LPV/r or ATV/r) • Confirmed plasma HIV-RNA >1000 copies/ml • Signed informed consent 4

  5. Thilao ANRS 12269 : Design Month-4 Decision Month-16 Outcomes Day-0 Inclusion Continue 2nd-line Continue 2nd-line Adherence reinforcement Switch to 3rd-line (2NRTI+darunavir 600 BID/r+raltegravir 400 BID) Inclusion criteria: VL >1000 copies/ml Month-4 Decision criteria: VL <400 copies/ml or >2 log decrease : Continue VL ≥ 400 copies/ml or < 2 log decrease : Switch Month-16 Outcomes: 1ary: Virol. success: <50 copies/ml 2ary: - Mortality • Resistance • Tolerance 5

  6. Thilao ANRS 12269 : Design Day-0 Inclusion Month-4 Decision Month-16 Outcomes Continue 2nd-line Continue 2nd-line Adherence reinforcement Switch to 3rd-line (2NRTI+darunavir 600 BID/r+raltegravir 400 BID) Adherencereinforcement = • Therapeuticeducation sessions (all patients) • + measureschosen by each patient among the followingones : Involvement of a relative, pillorganizer, weekly phone calls, alarmreminders, SMS, home visits, extra visits to the study center, support group, adjustment of ART drug doses, adjustment of non-ART drugs 6

  7. Viral load and genotypic testing Viral load monitoring : • Every 3-months • PROSPECTIVE, RESULTS PROVIDED IN REAL-TIME TO CLINICIANS • Month-3 resultused to inform Month-4 decision • Month-7, 10, 13 results : switch to 3rd-line at any time duringfollow-up if confirmed VL >1000 copies/ml Genotypicresistancetesting: • Plasma samplefrozen at Day-0 and Month-16 • Genotypictesting for all D-0 and M-16 sampleswith VL > 400 copies/ml • RETROSPECTIVE, RESULTS NOT AVAILABLE IN REAL-TIME TO CLINICIANS • Genotypictesting for all sampleswith VL > 400 copies/ml 7

  8. Definitions - Genotypic Sensitivity Score (GSS) • Number of drugs in ongoing regimen to which the patient’s virus has genotypic sensitivity - Month-4 decision appropriateness • Decision taken at Month-4 retrospectively judged on the basis of genotypes at Day-0 : - Inappropriate absence of switch: resistance to PI or GSS<2 - Inappropriate switch: sensitivity to PI and GSS=3 - Resistance accumulations • New resistance mutations occuring between Day-0 and Month-16 in patients with viral load >400 copies at Day-0 and Month-16 8

  9. Baseline characteristics, N=198 * The NRTIs were TDF-XTC in 52% of patients 9

  10. Month-4 decision Inclusion Month-4 decision Continue 2nd-line: N=130 (66%) 2nd-line • Death, 5 (2.5%) Switch to 3rd-line: N=63 (32%) 10

  11. Month-16 outcomes Inclusion Month-4 decision Month-16 outcomes Continue 2nd-line: N=130 (66%) • Overall, n (%) • Death: 15 (8%) • LTFU: 4 (2%) • VL <50 cp/ml: 101 (51%) • 50-400 cp/ml: 46 (23%) • >400 cp/ml:31 (17%) 2nd-line Switch to 3rd-line: N=63 (32%) 11

  12. Month-16 outcomes, by Month-4 decision Inclusion Month-4 decision Month-16 outcomes Continue 2nd-line: N=130 • Death: 6 (5%) • LTFU: 4 (3%) • VL <50 cp/ml:64 (49%) 50-400 cp/ml: 39 (30%) >400 cp/ml:17 (13%) 2nd-line • Death, 5 (2.5%) • Death: 4 (6%) • LTFU: 0 (0%) • VL <50 cp/ml:37 (59%) 50-400 cp/ml: 7 (11%) >400 cp/ml:14 (22%) Switch to 3rd-line: N=63 12

  13. Probability of first VL<50 over time, by Month-4 decision 82% 77% 13

  14. Other secondary endpoints, by Month-4 decision * 11 NRTI, 12 NNRTI, 8 PI ** 3 NRTI, 8 NNRTI, 5 PI, 0 RAL 14

  15. Discussion • In settings where viral load is routinely used for monitoring but routine genotypic testing is not available for real time use : • An intense adherence reinforcement phase, used as a tool to distinguish between patients who can still benefit from their current regimen and those who truly need third-line ART allowed to take appropriate decision of switching/ not switching in most patients • Resistance accumulation was rare • Third-line ART was well tolerated • Accessibility to viral load monitoring, to adherence reinforcement measures, and to third-line drugs should be reinforced 15

  16. Acknowlegments ANRS research site in Côte d’Ivoire • All patients who accepted to participate in the study Coordinating Investigators: R. Landman, Paris, France; SP. Eholié, Abidjan, Cote d’ivoire • ANRS: JF . Delfraissy, B. Bazin, G. Colin, P. Garcia • IMEA: PM. Girard, A. Benalycherif, B. Gadaleta • INSERM 1219/PACCI: X. Anglaret, J. Lecarrou, D. Gabillard, S. Karcher, L. N’Guessan, C. Nchot, E. Amani, A. Kouakou, R. Konan • GIP ESTHER: G. Raguin, C. Michon, A. Laurent, JM. Masumboko, A. Beugny • Trainer Forma Santé : C. Pinosa, N. Bernard, AM. Ane • Adherence group: C. Danel, C. Michon, L. Slama, A. Sawadago, R. Tubiana • SMIT Abidjan: E. Bissagnéné, F. Ello, F. Eboumou, Z. Diallo, Y. Siloué, F. Kouakou, J. Dano , M. Abanou • CePreF Abidjan: E. Messou, A. Anzian, P. Gouessé, J. Goli, A. Tchéhy, MC. Kassi • Day care Unit Bobo-Dioulasso: A. Sawadogo, L. Slama , J. Zoungrana, I. Soré, J.R. Traoré, G. Bado • CRCF Dakar and SMIT Dakar: M. Seydi, G. Laborde, M. Maynart, N. Gaye, M. Diallo, M. Basty • Cedres Abidjan: H. Menan, A. Emieme • Virology Unit (Necker et St Louis, Paris, Dakar): ML. Chaix, C. Rouzioux, C. Toure-Cane • Mali team: D. Minta, L. Tubiana, M. Fomba, A. Maiga, O. Dogoni, K. Kassogué, M. Cissé • Ouagadougou team: J. Drabo, I. Diallo, M. Congo • Scientific Advisory Board: PM. Girard (Chairman), E. Bissagnéné, B. Bazin, X. Anglaret, A. Desclaux, G. Raguin, C. Michon, C. Katlama, Y. Yazdapanah, E. Bissagnéné, R. Tubiana, E. Ouattara, ML. Chaix, AG. Marcellin, C. Touré-Kane, D. Minta, M. Seydi, AM. Maiga, G. Peytavin, Y. Coulibaly, A. Kambou-Sawadogo, I. Ba, A. Sangho, L. Slama 16

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