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Access to ARV …a vision for the next 10 years perspectives…

Access to ARV …a vision for the next 10 years perspectives…. Pedro Cahn.Isabelle Andrieux-Meyer Washington IAC 2012.MSF Satellite Putting our Best foot forward. Tuesday 24 th July. Disclosures. PC served as advisor for: Avexa Gilead J & J - Tibotec Merck/Schering Plough

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Access to ARV …a vision for the next 10 years perspectives…

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  1. Access to ARV …a vision for the next 10 yearsperspectives… Pedro Cahn.Isabelle Andrieux-Meyer Washington IAC 2012.MSF Satellite Putting our Best foot forward. Tuesday 24th July.

  2. Disclosures PC served as advisor for: • Avexa • Gilead • J & J - Tibotec • Merck/Schering Plough • ViiV (GSK & Pfizer)

  3. PUTTING OUR BEST FOOT FORWARD: Getting the best treatment to the most people possible at an affordable price • The impossible task…. • Future treatment options: WHAT, WHEN, HOW Cahn, Pedro Buenos Aires, Argentina 10 minutes

  4. Dream ART regimen • “Ideally this regimen would be so safe, simple, tolerable and durable that the need for switching to a new regimen would be very rare.” • The characteristics requested from HIV drugs are high level: in the future, due to scaling up and early treatment induction, HIV treatment will be given by community care providers, in decentralised health facilities or in the community. • Drugs have to be efficient and simple, tolerable, durable, compatible with pregnancy and with anti-tuberculosis regimen, affordable, potentially different from PrEP, and compatible for paediatric use. MSF Esther Solthis antiretroviral sequencing meeting report http://www.msfaccess.org/content/antiretroviral-sequencing-meeting-report

  5. FIRST LINE ART WORKS WELL:Registrational Treatment-Naive Clinical Trials: Cross-Study Comparison* HIV RNA <50 c/mL at Week 48 GS-103 QUAD (n=353)12 GS-102 QUAD (n=348)11 GS-103 ATV+RTV (n=355)12 STARTMRK RAL (n=281)8 GS-102 Atripla (n=352)11 ARTEMIS DRV+RTV (n=343)7 ECHO/THRIVE RPV (n=550)10 ECHO/THRIVE EFV (n=546)10 STARTMRK EFV (n=282)8 GS 934 EFV (n=244)4 ARTEMIS LPV/r (n=346)7 CASTLE ATV+RTV (n=440)6 ABT 730 LPV/r qd (n=333)5 NRTI backbone FTC/TDF3TC/ABC qd3TC+ABC bid3TC/ZDV3TC+TDF CASTLE LPV/r (n=443)6 ABT 730 LPV/r bid (n=331)5 GS-903 EFV (n=299)9 KLEAN FPV/r (n=434)14 KLEAN LPV/r (n=444)14 GS 934 EFV (n=243)4 CNA 30024 EFV (n=324)13 CNA 30024 EFV (n=325)13 SOLO FPV/r (n=322)2 MERIT ES MVC (n=311)3 MERIT ES EFV (n=303)3 SOLO NFV (n=327)2 CNA 30021 EFV (n=386)1 CNA 30021 EFV (n=384)1 5 % of Patients with HIV-1 RNA <50 copies/mL at Week 48 *This slide depicts data from multiple studies published from 2004-2012. Not all regimens have been compared head-to-head in a clinical trial

  6. Criteria for Prioritization • Safety/Efficacy • Tolerability • Durability • Stability • Convenience • Special populations • Cost Short-Term Priorities for ARV Drug Optimization WHO Meeting Report, London, 2011

  7. New drugs in the pipeline: Approval expected shortly • Elvitegravir* • Cobicistat • Quad • Dolutegravir. • FDC ABC-3TC – DTG in progress • FDC Maraviroc - ABC- 3TC or TDF-FTC • FDC LPV/r -3TC Approval expected in 2012 Approval expected in 2013 In progress * Needs boosting

  8. New drugs, early phases RTIs • TDF prodrug • Elvucitabine • Festinavir • Amdoxovir • Apricitabine • Lersivirine (NNRTI) – Phase II Entryinhibitors • BMS 068 (Attachmentinhibitor) • Cenicriviroc (CCR5 inhibitor) • Ibalizumab (CD4 monoclal Ab) • Pro-140 (CCR5 monoclonal Ab) Other: • CTP-518 (Unboosted PI) • S/GSK 744 (Integrase inhibitor) • SPI-452 (Pharmacokineticenhancer) • On hold: • Racivir • Fozivudine • RDEA 806 (NNRTI)

  9. ART Sequencing treatment naïve adults NOW &MEDIUM TERM PRIORITIES (3-6 years) for resource limited settings • Today the best first line is TDF/3TC/ EFV. • Most probably TDF/3TC /EFV will still be first line in the medium term , considering the time still needed to fully implement this regimen. • The added value of the following drugs and formulations for resource limited settings will have to be carefully assessed: • new combinations: • QUAD ( EVG-COB-TDF/ pro-TDF-FTC)*, • Dolutegravir-abacavir-lamivudine**, • rilpivirine based combination***. • PI first line ( ATV/r, DRV/r) how to overcome their interaction with rifampicine, strategic decision will have to be made/ DRV as first or second line component. • TDF pro-drugs ( GS 7340) • Integrase inhibitors first line • Availability of rifabutine-TB co-formulations. • Take the best of pipeline development! Caveats:: * DDIs, Creatinine signal ** HSR *** Limited to VL<100,000 copies

  10. ART sequencing second line priorities: now and in the medium term Now:ATV/r co-formulation or DVR/r based co-formulations. ATZ/r FDC implementation: should have the priority. Explore : Access RIFABUTIN, PK studies ATZ/r and rifabutine -TB FDC : very important DARUNAVIR optimization and price reduction for a FDC. Clarify TB association. Follow development of DOLUTEGRAVIR for L2 companion drug to DAR. Explore alternative boosters . TB option: RAL-2NUCs.Clarify DVR & TB drugs. Clarify place for NRTIs. Best SALVAGE regimen: DRV/r/RAL/ETV

  11. Sequencing for infants and children Approach treatment of HIV +ve children as one ie. same treatment for ARV exposed or non exposed. Clear need for alignment with adult regimen but tx strategies for the younger children will be different Babies and infants below 2-3yo will need intensive ART either with: 3NRTIs + 1NNRTI or PI + 2NRTIs >2-3yo, alignment of treatment with adults ie. TDF/3TC/EFV Children failing PI based regimen: DVR/r+DLG? for the medium term future?

  12. Recapitulation ART sequencing

  13. Task shifting, decentralisation and scaling –up at community level • Health care providers will have to work in a more decentralised way, through health posts at the community level, and services will need to become family-friendly and mainly community health worker or patient group-based

  14. Pre-exposure prophylaxis in 2012 • The best prevention is ART for HIV+ patients. • Drugs used for PreP should preferably be different from drugs used for treatment. • Topical PreP show poor efficacy results so far. • Reliable PreP strategies: condoms, circumcision. Eventually TDF/FTC oral QD for special vulnerable groups or individuals willing to increase their protection ( MSM, CSW for example, or some sero-discordant couples) • Explore new classes like entry inhibitors for PreP

  15. So, how should a “best candidate” look? • QD • Welltolerated • Potent • Highgeneticbarrier • Lowrisk of DDIs • FDC friendly • Heatstable • Lowamount of API required (cost) • Pediatricformulationfeasible • Specialpopulations

  16. My list of short-term best candidates(2012-2014) • QUAD pill • Dolutegravir • Dolutrii FDC • Darunavir/Cobicistat FDC • New heat-stableFDCswithexistingdrugs My bonustrack: Class-sparingstrategies

  17. Themainchallenges • Simplification, treatmentstandardizationincluding PW, kids and specialpopulations • Cost • Logistics, procurement, infrastructure • Humanresources • Earlydetection • Monitoring, VL, PoCtechnologies • Retention in care • Integration of services (TB, Hepatititis, STDs, SRH, NCDs)

  18. Acknowledgments to all MSF patients and care givers Special thanks to all participants to the ART sequencing meeting: A.Calmy, A.Hill, A.Levin, A.Owen, A.Gayot, A.Heinzelman, A.Antierens, B.Milani, B.Coriat, B.Hirschel, B.Waning, C.Malavazzi, C.Ferreyra, C.Katlama, C.Jamet, C.Rouzioux, C.McLure, D.Gibb, D.Descamps, D.Blair, E.t’Hoen, E.Katabira, E.Jambert, E.Comte, E.Goemaere, E.Burrone, E.Casas, E.RErmantraut, F.Huber, F.Verhoustraeten, G.Ferlazzo, G.Raguin, H.Lee, J.Lee, J.Rigal, J.Lujan, L.Szulilin, M.Pujades, M.Gale, M.Lallemant, M.Vitoria, M.Serafini, M.Childs, M.Vilk, N.Sugandhi, N.Ford, N.Otwoma, O.Kaiser, P.Munderi.Auberson, P.Cahn, P.Clayden, R.Papadopoulou, R.Teck, R.Malyuta, S.Essajee, S.Lynch, S.Collins, S.Crowley, S.Rannard, S.Becker, S.Balkan, T.Roberts, V.Calvez, Y.Yazdanpanah Acknowledgments

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