Optimizing and simplifying the toolkit (drugs, dosing, and diagnostics) and delivery of ART Dr Eric Goemaere Regional TB/HIV Advisor MSF South Africa

Bending the curves Reducing clinical workload  Bending the epidemic curve  Distributing tasks Increasing patient autonomy & adherence  Long term community based chronic care Reducing pill burden and toxicities  ARV dosage optimization  New formulations  New ARVs

Doctors Increased coverage Lower Cd4 threshold PHC decentralised care, nurse based CHW supported Patient self management Reduced clinical time /patient Patient friendly regimen: easy to use low toxicity, forgiving Patient-centered efficiency

Bending the epidemic curve Moving from emergency to a chronic phase Khayelitsha Transition needs to happen as soon as possible -> early aggressive approach ( emergency phase)

Distributing tasks Consultation Clinical screening Psycho social support Drug re-fill Clinical screening Psycho social support Drug re-fill

What will Khayelitsha look like in 10 years ? Pop. 500,000 (250,000 adults) ANC prevalence 30% =est ,000 HIV+ Incidence =est new infections/year

Khayelitsha Facility-linked, PLWHA-led 'Adherence Clubs' ClinicCommunity based Clubs Monthly doctor/nurse appointment allocated to one club Counselor and PWHLA “facilitator” Peer support Individual consultationGroup screening Time: 1 day in the clinic2 hours Monthly refills2-3 months refills General education, health talksSpecific education & discussion 12 visits a year6 visits, with flexibility (family member can pick up meds)

Thyolo, Malawi Decentralization to health posts Outreach from existing health centers if > 10 km Minimum package of HIV services ARV refills dispensed by lay health workers (HSAs) for stable patients on HAART Staffing: one community nurse and 2-3 HSAs

Tete, Mozambique Community-HAART Groups PLWHA driven Support group w/ ART provision Rep. Elecetd to collect ARV's Maximum 6 patients Between June 08 and Dec 09  199 CHG formed 1253 patients  95.4 % RIC  1.7 % died  0.2 % LTFU  1.9 % TFO  0.8 % returned to HC

Dose optimization Objectives:  Reduce patient toxicity  Reduce pill burden  Reduce costs d4T: from 40 mg to 30 mg BID dose for all patients AZT was initially marketed as 250mg bid in Europe until late 1990s. Dose still available for sale in Europe For several HIV drugs, Phase 2 data showed no difference in efficacy between doses, but higher doses were selected for Phase 3 and registration (EFV, LPV/r, RAL, 3TC) In drug development, dosage selection is made early and not reassessed later

Source: Charlotte Schultz, GFJooste ID referral unit, cape Town Reducing D4T dosage Impact on regimen safety

Potential Dose Optimization Investigations _________________________________________________________ Drug Current doseTarget Optimised dose _________________________________________________________ ZDV300mg BID200 mg BID 3TC 300 mg OD150 mg OD ** EFV 600 mg OD400 mg OD ** LPV/r400/100 mg BID 200/100 or 200/150 BID ** ATV/r300/100 mg OD 300/50 or 200/50 mg OD DRV/r600/100 BID 400/50 mg OD (PI naives) RTV 100mg (booster) 50mg (booster) RAL 400mg BID mg BID _________________________________________________________ ** Encore trials : funded and support from Bill and Melinda Gates Foundation, University of New South Wales and Clinton Health Action Initiative Source: Andrew Hill

Long term therapeutic strategy Specific treatment paradigm for high prevalence LRC contexts ? Future perspectives  Moving away from a sequential paradigm to Induction/maintenance paradigm ? Drug required profile  Potent regimen for induction ( Raltegravir/Darunavir/r)  Systematic switch to maintenance with no monitoring  Long half life, forgiving regimen( PI based ) for maintenance  Safe, minimal side effects,  NRTI sparing

New drugs, new formulations? Promising drugs  Rilpivirine (Tibotec) – NNRTI, (Phase III)  low dose 25mg, long half life 38 hours,  Elvucitabine (Achillion) – NRTI, (Phase II)  low dose 10mg, long half life 49hrs, safety efficacy data?  CMX 157 (Chimerix) – (Phase I),  prodrug of TDF,more potent than TDF++, low dose, safety efficacy data?  S/GSK (ViiV) (Phase IIb)  – Integrase Inhibitor, low dose 50mg, no booster required, long half life 30 hours, safety efficacy data?

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